PROJECT STAFF
Paul Shekelle, MD, PhD
Task Order Director
Erin G. Stone, MD
Principle Investigator
Steven Kania, MD
Investigator
Scott Weingarten, MD, MPH
Investigator
Margie Snape, MLS
Research Librarian
Michael Hirt, MD
screening/abstraction
Tommy Tomizawa, MD
Gregory Dorn, MD
Luca De Simone, MD
Article
Acknowledgements:
We would like to thank Gunter Rieg, M.D. for his help in translation of the German studies,
and Irma Porras, Vanessa Walker and Shannon Rhodes for secretarial assistance.
CONTENTS
EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
METHODS ................................................................................................... 1 1
CLINICAL QUESTIONS ...................................................................................................................... 11
LITERATURE REVIEW....................................................................................................................... 14
Inclusion and Exclusion Criteria ..........................................................................................................................................................1 5
Article Selection and Abstraction ........................................................................................................................................................1 5
Critical Appraisal Method for Prognostic Articles .........................................................................................................................1 6
Critical Appraisal Method for Diagnostic Articles .........................................................................................................................1 7
Critical Appraisal Method for Treatment Articles ............................................................................................................................1 8
Evidence Synthesis...................................................................................................................................................................................1 9
RESULTS .................................................................................................... 2 0
DISTRIBUTION OF EVIDENCE.............................................................................................................. 20
FIGURE 1. ARTICLE SELECTION PROCESS ............................................................................................. 21
Question 1: Which measure of nutritional status best predicts patient morbidity/ mortality in chronic
dialysis patients?...............................................................................................................................................................2 2
Question 2: Which measure is the best diagnostic test for protein/ calorie nutritional status in chronic
dialysis patients?...............................................................................................................................................................2 2
Question 3: What is the effect of acid/ base status on nutritional measures in chronic dialysis patients? .....................2 3
Question 4: Which levels of intake of protein and calories in chronic dialysis patients produce the lowest
morbidity/ mortality (also optimal changes in nutritional parameters and best nitrogen
balance)?...............................................................................................................................................................................2 6
Question 5: Which levels of intake of protein and calories in predialysis patients produce the lowest
morbidity at the initiation of dialysis?........................................................................................................................2 7
Question 6: How does resting energy expenditure in dialysis patients compare with resting energy
expenditure in patients not on dialysis?.....................................................................................................................2 8
Question 7: Which nutritional interventions produce the lowest morbidity/ morality or the most optimum
changes in nutritional status in dialysis patients?..................................................................................................2 8
Question 8: Is interdialytic weight gain a good measure for dietary compliance or a good prognostic
indicator in dialysis patients? .......................................................................................................................................2 9
Questions 9-12: Carnitine Supplementation.....................................................................................................................................2 9
Pediatrics Question 1: Which measure of nutritional status best predicts patient morbidity/ mortality (and
growth rate in children) in chronic dialysis patients?............................................................................................3 3
Pediatrics Question 2: Which measure is the best diagnostic test for protein/ calorie nutritional status in
chronic dialysis patients? ...............................................................................................................................................3 4
Pediatrics Question 3: What is the effect of acid/ base status on nutritional measures in chronic dialysis
patients? ...............................................................................................................................................................................3 4
Pediatrics Question 4 and Question 5: Which levels of intake of protein and calories in chronic dialysis
produce the lowest morbidity/ mortality? Which levels of intake of protein and calories in
predialysis patients produce the lowest morbidity at the initiation of dialysis? ...........................................3 4
Pediatrics Question 6: How does resting energy expenditure in dialysis patients compare with resting
energy expenditure in patients not on dialysis?.......................................................................................................3 5
Pediatrics Question 7: Which nutritional interventions produce the lowest morbidity/ mortality (and best
growth rate in children) or the most optimum changes in nutritional status in dialysis
patients? ...............................................................................................................................................................................3 5
Pediatrics Question 8: Is interdialytic weight gain a good measure for dietary compliance or a good
prognostic indicator in dialysis patients? .................................................................................................................3 6
Pediatrics Question 13: Does growth hormone therapy improve morbidity/ mortality in pediatric chronic
dialysis patients?...............................................................................................................................................................3 6
Pediatric Question 14: Does vitamin or mineral supplementation improve morbidity/ mortality in pediatric
dialysis patients? (Calcium, magnesium, and vitamin D were not examined.) ..................................................3 7
SUMMARY .................................................................................................. 3 8
IN-TEXT REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2
APPENDIXES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 5
APPENDIX A: GLOSSARY................................................................................................................... 46
APPENDIX B: TECHNICAL EXPERTS - NKF DOQI NUTRITION IN DIALYSIS WORKGROUP ............................. 56
APPENDIX C: SEARCH STRATEGIES..................................................................................................... 58
Strategies for Questions 1-8 ...................................................................................................................................................................5 8
Search strategy for Questions 9-12.......................................................................................................................................................6 1
Search strategy for Question 13 , 14 and IGF (Pediatric Question 1) ........................................................................................6 2
i
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES ............................................................................ 63
References for Questions 1-12 - Adults...............................................................................................................................................6 3
References for Pediatric Sections...........................................................................................................................................................8 5
APPENDIX E: ABSTRACTION FORMS .................................................................................................... 93
NKF Prognostic Article Abstract Form ..............................................................................................................................................9 3
NKF Diagnostic Article Abstract Form ..............................................................................................................................................9 5
NKF Treatment Article Abstract Form .................................................................................................................................................9 7
APPENDIX F: TREATMENT ARTICLE QUALITY SCORE ALGORITHM...........................................................100
APPENDIX G: EVIDENCE TABLES.......................................................................................................102
ii
EXECUTIVE SUMMARY
INTRODUCTION
Chronic dialysis is a common and expensive therapy for end stage renal disease. The number
of patients prescribed this therapy is increasing with time. Using a variety of measures, a
number of articles studying patients in both the US and other countries have reported the
prevalence of malnutrition in this population to range from 25% to 73%. Malnutrition increases
morbidity, mortality, and cost, and produces growth retardation in children. It is therefore
important to determine methods to adequately assess the nutritional status of dialysis patients,
to prevent malnutrition from occurring in these patients, and to adequately treat malnutrition
once it is discovered. This evidence report addresses nutritional prognostic, diagnostic, and
treatment issues in dialysis patients.
M ETHODS
We performed a systematic review to assemble and critically appraise relevant studies answering
the clinical questions of interest. The technical experts for this Evidence Report are the members
of the National Kidney Foundation (NKF) Dialysis Outcomes Quality Initiative (DOQI)
Workgroups. With their input we formulated the following key clinical questions:
Question 1. Which measure of nutritional status best predicts patient morbidity/ mortality (and
growth rate in children) in chronic dialysis patients?
Question 2. Which measure is the best diagnostic test for protein/ calorie nutritional status in
chronic dialysis patients?
1
Question 3. What is the effect of acid/ base status on nutritional measures in chronic dialysis
patients?
Question 4. Which levels of intake of protein and calories in chronic dialysis produce the lowest
morbidity/ mortality?
Question 5. Which levels of intake of protein and calories in predialysis patients produce the
lowest morbidity at the initiation of dialysis?
Question 6. How does resting energy expenditure in dialysis patients compare with resting
energy expenditure in patients not on dialysis?
Question 7. Which nutritional interventions produce the lowest morbidity/ mortality (and best
growth in children) or the most optimum changes in nutritional status in dialysis patients?
Question 8. Is interdialytic weight gain a good measure for dietary compliance or a good
prognostic indicator in dialysis patients?
Question 9. Which measure of L-carnitine nutritional status best predicts patient morbidity/
mortality in chronic adult dialysis patients?
Question 10. What are the best measures of L-carnitine nutritional status in chronic adult
dialysis patients?
Question 11. Does L-carnitine supplementation in chronic adult dialysis patients improve
morbidity/ mortality?
2
Question 12. What are the toxic/ adverse effects of L-carnitine in adult chronic dialysis patients?
Question 13. Does growth hormone therapy improve morbidity/ mortality in pediatric chronic
dialysis patients?
Question 14. Does vitamin or mineral supplementation improve morbidity/ mortality in
pediatric dialysis patients? (Calcium, magnesium, and vitamin D were not examined.)
A structured database search of two computerized bibliographic databases (MEDLINE,
EMBASE) was performed in collaboration with a librarian experienced in searching
computerized bibliographic databases and performing “evidence-based” systematic reviews.
We also hand-search the Journal of Renal Nutrition since it was not indexed in these
bibliographic databases. Additionally, referrals from the technical experts were reviewed. For
Questions 9-12 an extensive carnitine bibliography was provided by Sigma Tau, Rome, Italy.
Articles addressing the clinical questions were included in the selection steps detailed below.
Animal studies, letters, editorials, reviews, case reports, and abstracts of meeting proceedings
were excluded.
After loading articles from MEDLINE, EMBASE, technical expert referrals, and the Sigma Tau
bibliography into an electronic database, one reviewer performed an initial title review and
selection. Two independent reviewers then selected articles based on article abstracts. Selection
disagreements were resolved by consensus. English language articles selected at the abstract stage
were then reviewed and selected by two independent reviewers. Information was abstracted
from the articles by one abstracter and verified by a second. Articles that were rejected at this
stage were coded using the following codes:
3
R1: Editorial, letter, review, case report, article published as abstracts
R2: Article doesn’t answer clinical question of interest
R3: Article doesn’t have study design of interest
R4: Pediatric Article (rejected from the adult questions only)
R5: Not human
R6: Adult article (rejected from the pediatric questions only)
English titles, and English abstracts when available, of selected foreign language articles were
sent to all technical experts for review. A foreign language article was abstracted by someone
fluent with that particular language if any technical expert indicated an article would potentially
contribute to the evidence in a particular area.
Because of the volume of accepted articles, further selections were made based on article
study design. For prognostic articles, only those with prospective cohort or historical
prospective cohort designs were included for further analysis. For diagnostic articles, only
those where the authors compared a test with what they considered to be a gold standard for
nutritional status were included for further analysis. For treatment articles, only those with a
prospective design with concurrent controls were included for further analysis. (These
restrictions did not apply to the carnitine sections or to the pediatric sections.) After article
abstraction, evidence tables were produced from a subset of abstracted data elements and
presented to the technical experts (also called workgroups) during meetings in Los Angeles in
August 1998 and January 1999. The technical experts accepted or rejected articles based on
the study methods, and adequacy in addressing the clinical questions.
4
R ESULTS
The initial literature search identified 19,272 MEDLINE and 4,943 EMBASE titles. In addition,
the technical experts referred 134 articles for review, and the Sigma Tau bibliography contained
138 references not found by other means. This review yielded 24,487 titles. Of these, 22,362
titles were rejected, leaving 2,125 titles. Abstracts of these articles were reviewed and 1,021 were
rejected, thus leaving 1,104 articles. One hundred and seventy of these were foreign language
articles whose titles and abstracts were sent to the technical experts. Of these, 102 were not
selected for further evaluation, 2 were selected but could not be translated, and 66 were further
evaluated. Of the 934 English language articles, 29 were unobtainable, leaving 971 English and
foreign language articles to be abstracted Of these, 640 were rejected (R1-R6) and the remaining
331 were sent to the technical experts along with evidence tables for these articles created from
the abstraction forms. The technical experts rejected 81 articles either because the article did not
adequately address a clinical question of interest or because the article was of poor study design,
thus leaving 250 accepted articles.
Question 1: Which measure of nutritional status best predicts patientmorbidity/
mortality in chronic dialysis patients?
We identified 46 studies which assessed the value of nutritional measures as predictors of
morbidity/ mortality in patients on chronic dialysis. Many articles studied albumin and
anthropometrics as prognostic factors, with other factors being less well studied. There is
consistent evidence that serum albumin is related to mortality in dialysis patients. Other
prognostic factors have been studied less frequently and/ or have had less consistent results.
5
Question 2: Which measure is the best diagnostic test for protein/ calorie
nutritional status in chronic dialysis patients?
Our literature search identified 29 studies pertaining to diagnostic tests for protein/ calorie
nutritional status. A consistent gold standard for the diagnosis of nutritional status in dialysis
patients was absent. Given this limitation, some support was found for the validity of serum
albumin, pre-albumin, creatinine, protein catabolic rate (PCR), protein equivalent of total
nitrogen appearance (PNA), the subjective global nutritional assessment (SGA),
anthropometric measurements, the dual x-ray photon absorptiometry (DEXA), and transferrin.
Question 3: What is the effect of acid/ base status on nutritional measures in
chronic dialysis patients?
Nine studies dealing with acid/ base status and nutrition in general supported the hypothesis
that correcting acidosis improved nutritional status.
Question 4: Which levels of intake of protein and calories in chronic dialysis
patients produce the lowest morbidity/ mortality (also optimal changes in
nutritional parameters and best nitrogen balance)
The 16 articles identified contained primarily nitrogen balance articles and in general indicate
that a dietary protein intake of 1.2g per kilogram per day is necessary to avoid nitrogen
imbalance.
Question 5: Which levels of intake of protein and calories in predialysis patients
produce the lowest morbidity at the initiation of dialysis?
Two meta-analyses assessing the effect of a low protein diet on predialysis patients both
reached the conclusion that such diets have a significant mortality benefit.
6
Question 6: How does resting energy expenditure in dialysis patients compare
with resting energy expenditure in patients not on dialysis?
The gold standard for the five articles selected was indirect calorimetry and the majority of
evidence indicates there is little difference in resting energy expenditure between dialysis
patients and patients not on dialysis.
Question 7: Which nutritional interventions produce the lowest morbidity/
morality or the most optimum changes in nutritional status in dialysis patients?
These 18 articles contained studies of both enteral and parenteral supplementation as well as
counseling. Results were inconsistent and no conclusion could be drawn.
Question 8: Is interdialytic weight gain a good measure for dietary compliance or
a good prognostic indicator in dialysis patients?
The 12 identified articles did not support a clinically important correlation between interdialytic
weight gain and dietary compliance or patient outcomes.
Questions 9-12: Carnitine Supplementation
We identified 33 studies where serum triglycerides were the outcome, five studies where
cardiac function and arrhythmia were the outcome, six studies where symptoms of malaise
asthenia, muscle cramps, weakness and fatigue were the outcome, five studies where
exercise capacity and muscle strength were the outcome, and 10 studies where anemia was
the outcome. This evidence on potential beneficial effects of carnitine is moderately extensive
but of uneven quality. Sufficient evidence to prove a benefit for carnitine was not found for
any outcome. The outcome with the best evidence of benefit was anemia. Several clinical
trials reported statistically significant improvements in hematocrit or decreases in
erythropoietin requirements. However, in none of these studies was the effect on anemia the
primary outcome, so these results must be viewed with caution as results of secondary
7
outcomes usually are known to overestimate efficacy. There is no evidence that
administration of carnitine in standard doses is associated with side effects.
Pediatrics Questions 1-14:
The evidence specific to pediatric patients was very sparce, with the exception of growth
hormone. One placebo-controlled double blind cross over trial of growth hormone in
prepubertal children with chromic renal failure provided strong evidence that growth hormone
treatment could greatly improve height velocity in such children. Other studies reported that
the improvement in linear growth in patients treated with dialysis is not as great as that
observed in patients with stable chronic renal failure and that the gain in height across
subsequent years is diminished.
C ONCLUSION
A large number of studies have been published in the medical literature on nutrition in dialysis
patients. Through the series of selection steps detailed above, approximately 1 in 20 of the
24,487 articles obtained from various sources was selected for data abstraction. Of these,
approximately 3% were unavailable, and two thirds were further rejected once the article was
read and evaluated. Of the remaining one third (331 articles), the technical experts rejected
approximately 1 in 4, leaving 250 accepted articles. Of these 250 accepted articles, pediatric
nephrology patients were the subjects in approximately one fourth, with adult patients being the
subjects in the remaining three fourths. There is sufficient evidence of validity for some
diagnostic, prognostic, and treatment procedures. This report will provide the evidence for the
development of clinical practice guidelines by the Nation Kidney Foundation Dialysis Outcomes
Quality Initiative.
8
INTRODUCTION
Of the nearly 200,000 patients in the US with end stage renal disease (ESRD) in 1990, 70% were
receiving either hemodialysis or peritoneal dialysis as renal replacement therapy (1). The
estimated cost of care for all patients with ESRD in 1990 was US$7.26 billion. It is estimated
that nearly 300,000 patients in the US will have ESRD in the year 2000, with an attendant rise in
the costs of care. The number and cost of patients with ESRD worldwide are even greater.
The prevalence of malnutrition in dialysis patients has been studied in various countries using
various methods. Anthropometric measures and albumin were significantly below normal in 37%
to 70% of hemodialysis patients in Thailand (2). Eighty-two percent of continuous ambulatory
peritoneal dialysis (CAPD) patients in Mexico were found to be malnourished (3). Using
subjective global assessment, serum chemistries, and anthropometric measures, 51% of elderly
Italian dialysis patients were found to be malnourished (4). In Pakistan, 34% to 70% of
hemodialysis patients were found to be malnourished when assessed by albumin levels and
various anthropometric measures (5). Malnutrition in Spanish hemodialysis patients was found
to range from 40% to 73% (6; 7), and was found to be 54% in Denmark (8). A number of studies
in the US have found the prevalence of malnutrition to range from 25% to 70% using a variety of
assessment tools including anthropometric measures, blood tests, and composite and global
assessments (9-12). One US study, however, found many patients to have anthropometric
measurements not dissimilar to those in the general population (13).
9
A number of causes have been proposed for malnutrition in dialysis patients. These include the
catabolic state of dialysis, the loss of nutrients during the dialysis procedure, the predialysis
protein-restricted diet frequently prescribed, abnormal metabolism of nutrients, and dialysisinduced anorexia (14). Malnutrition increases morbidity, mortality, and cost, and produces
growth retardation in children. Thus, it in incumbent on the nephrology community to determine
methods to adequately assess the nutritional status of dialysis patients, to prevent malnutrition
from occurring in these patients, and to adequately treat malnutrition once it is discovered. To
these ends, the National Kidney Foundation has commissioned a systematic review of nutrition
in chronic renal failure, the details of which are contained in this report.
10
METHODS
We performed a systematic review that “involves the application of scientific strategies, in ways
that limit bias, to the assembly, critical appraisal, and synthesis of all relevant studies that
address a specific clinical question.” (15; 16) A glossary of terms related to systematic reviews is
listed in Appendix A.
C LINICAL Q U E S T I O N S
With the guidance of the technical experts of the National Kidney Foundation (NKF) Dialysis
Outcomes Quality Initiative (DOQI) Workgroup (Appendix B) we formulated the following
clinical questions:
Question 1. Which measure of nutritional status best predicts patient morbidity/ mortality (and
growth rate in children) in chronic dialysis patients? The technical experts chose to review only
the following measures:
•
Pre-albumin
•
Subjective Global Assessment
•
Albumin
•
Dietary history
•
Anthropometric measures (height, weight,
•
Cholesterol
skinfold thickness, body mass index
•
Transferrin
(BMI), percent of normal body weight,
•
PCR/PNA
percent of ideal body weight, post-dialysis
•
Prognostic nutrition index
body weight)
•
Acute phase protein (C-reactive protein)
•
Bio-electric impedence
•
Alpha-1 glycoprotein
•
Urea nitrogen appearance
•
DEXA
•
Pre-dialysis creatinine
•
IGF in pediatric patients
•
More than 1 of the above measures
11
Question 2. Which measure is the best diagnostic test for protein/ calorie nutritional status in
chronic dialysis patients? The technical experts chose to review only the following measures:
•
Pre-albumin
•
Subjective Global Assessment
•
Albumin
•
Dietary history
•
Anthropometric measures (height, weight,
•
Cholesterol
skinfold thickness, body mass index
•
Transferrin
(BMI), percent of normal body weight,
•
PCR/PNA
percent of ideal body weight, post-dialysis
•
Prognostic nutrition index
body weight)
•
Acute phase protein (C-reactive protein)
•
Bio-electric impedence
•
Alpha-1 glycoprotein
•
Urea nitrogen appearance
•
DEXA
•
Pre-dialysis creatinine
•
IGF in pediatric patients
•
More than 1 of the above measures
Question 3. What is the effect of acid/ base status on nutritional measures in chronic dialysis
patients?
Question 4. Which levels of intake of protein and calories in chronic dialysis produce the lowest
morbidity/mortality? The technical experts chose to also review the following:
•
The most optimum changes in nutritional status using measures from question #1
above?
•
Best nitrogen balance
•
Best growth in children
Question 5. Which levels of intake of protein and calories in predialysis patients produce the
lowest morbidity at the initiation of dialysis? (Though this question was addressed by both
adult and pediatric groups, the pediatric group chose to use these articles to inform Question 4,
while the adult group chose to write a separate guideline for this section.)
12
Question 6. How does resting energy expenditure in dialysis patients compare with resting
energy expenditure in patients not on dialysis?
Question 7. Which nutritional interventions produce the lowest morbidity/mortality (and best
growth in children) or the most optimum changes in nutritional status in dialysis patients? The
technical experts chose to review the following measures from Question 1 above.
•
Intradialytic supplementation
•
Intra-PD supplementation
•
Tube feeding
•
Oral supplements
•
Nutrition counseling
•
Acid/base correction
•
Intravenous supplementation
Question 8. Is interdialytic weight gain a good measure for dietary compliance or a good
prognostic indicator in dialysis patients?
Question 9. Which measure of carnitine nutritional status best predicts patient morbidity/
mortality in chronic adult dialysis patients? The technical experts chose to review only the
following measures:
•
Plasma carnitine levels
•
Plasma acylcarnitine levels
•
Muscle carnitine levels
Question 10. What are the best measures of carnitine nutritional status in chronic adult dialysis
patients? (Question 11 was addressed first, with Question 10 being addressed if carnitine
supplementation at any carnitine/acylcarnitine level was felt to change outcomes.) The technical
experts chose to review only the following measures:
•
Plasma carnitine levels
•
Plasma acylcarnitine levels
13
•
Muscle carnitine levels
Question 11. Does carnitine supplementation in chronic adult dialysis patients improve
morbidity/ mortality? The technical experts chose to also review the following::
•
Hypertriglyceridemia
•
Exercise tolerance
•
Anemia
•
Left ventricular dysfunction
•
Intradialytic dysrythmias
•
Quality of life
Question 12. What are the toxic/ adverse effects of L-carnitine in adult chronic dialysis patients?
Question 13.
Does growth hormone therapy improve morbidity/ mortality in pediatric chronic
dialysis patients?
Question 14.
Does vitamin or mineral supplementation improve morbidity/ mortality in
pediatric chronic dialysis patients? (calcium, magnesium, and vitamin D were not examined.)
L ITERATURE R E V I E W
A structured database search of 2 computerized bibliographic databases (MEDLINE, EMBASE)
was performed with the following specifications:
•
Language: English and non-English articles
•
Dates: 1966 through 1997
•
Subjects: Human.
•
Article types: letters, editorials, reviews, case reports, and abstracts of meeting
proceedings were excluded.
The search was performed in collaboration with a librarian experienced in searching computerized
bibliographic databases and performing “evidence-based” systematic reviews. The MEDLINE
search strategies are detailed in Appendix C. The EMBASE strategies were similar.
14
We also hand-search the Journal of Renal Nutrition since it was not indexed in the bibliographic
databases listed above. Additionally, referrals from technical experts were reviewed. For
Questions 9-12, an extensive carnitine bibliography was provided by Sigma Tau, Rome, Italy.
Inclusion and Exclusion Criteria
Articles meeting the specifications listed above, and addressing at least 1 of the clinical questions
detailed above were included. All others were excluded.
Article Selection and Abstraction
After loading articles from MEDLINE, EMBASE, technical expert referrals and the Sigma
Tau bibliography into an electronic database, one reviewer performed an initial title review of
these articles, applying the above inclusion and exclusion criteria. Abstracts were requested
for all articles accepted at the title screening phase. Two independent reviewers then
screened the abstracts and applied the above inclusion and exclusion criteria. Selection
disagreements were resolved by consensus. English language articles accepted at the abstract
screening phase were obtained and divided into the appropriate sections (see above) based on
the clinical question the article addressed. These articles were then reviewed by two
independent reviewers. Information was abstracted from the articles (see below) by one
abstracter and verified by a second. Disagreements were resolved by consensus. Articles
rejected at the abstraction stage were coded using the following:
R1: Editorial, letter, review, case report, article published as abstracts
R2: Article doesn’t answer clinical question of interest
R3: Article doesn’t have study design of interest
R4: Pediatric Article (rejected from the adult questions only)
R5: Not human
R6: Adult article (rejected from the pediatric questions only)
15
Article publication language was not limited to English in order to increase precision and
reduce systematic errors (17), and because of the potential publication bias for positive studies
in the English literature (18). After discussing the process of foreign language article selection
with the technical experts, we decided to send the English titles, and English abstracts when
available, to all technical experts for review. A foreign language article was abstracted by
someone fluent with that particular language if any technical expert indicated that an article
would possibly contribute to the evidence in a particular area.
Because of the volume of accepted articles, selections were further made based on article
study design. For prognostic articles, only those with prospective cohort or historical
prospective cohort designs were included for further analysis. For diagnostic articles, only
those where the authors compared a test with what they considered to be a gold standard for
nutritional status were included for further analysis. For treatment articles, only those with a
prospective design with concurrent controls were included for further analysis. (These
restrictions did not apply to the carnitine sections or to the pediatric sections.)
After article abstraction (see below), evidence tables were produced from a subset of
abstracted data elements and presented to the technical experts during meetings in Los
Angeles in August, 1998 (adult technical experts), January, 1999 (pediatric technical experts),
and during a series of subsequent conference calls. The technical experts accepted or
rejected articles based on the study methods and adequacy in addressing the clinical questions.
The article selection process is detailed in Appendix D. The final selected articles are listed in
Appendix E.
Critical Appraisal Method for Prognostic Articles
For each prognostic article (Questions 1, 3, 4, 5, and 8), we abstracted data to answer the
following questions (19):
16
•
What was the type of study?
•
What were the three most frequently occurring co-morbid conditions?
•
Was there a representative and well-defined sample of patients at a similar point in the
course of disease?
•
What was the follow-up time period?
•
Were the outcome criteria objective and application of them unbiased?
•
Was adjustment made for important known prognostic factors?
•
What were the results?
In addition, we abstracted a number of data elements that addressed study population and
dialysis characteristics that might have affected the study results:
•
Number of patients at start of study
•
Years on dialysis
•
Age of patients
•
Type of dialysis
•
Dialysate
•
Membrane and whether it was reused
•
Dialysis schedule
•
For HD, type of vascular access
•
Economic status
•
Race
•
Residual renal function
A copy of the article abstraction form is in Appendix F.
Critical Appraisal Method for Diagnostic Articles
For each diagnostic article (Questions 2 and 6), we abstracted data to answer the following
questions (20; 21):
•
What was the type of study?
•
What were the three most frequently occurring co-morbid conditions?
17
•
Was there an independent blind comparison with a reference (gold) standard?
•
Did results of the test being studied influence the decision to perform the reference
standard?
•
Was the spectrum of patients in the study similar to the spectrum seen in dialysis
centers?
•
Was the test methodology described well enough to be reproducible?
•
What were the results?
In addition, we abstracted a number of data elements that addressed study population and
dialysis characteristics that might have affected the study results. These were the same as for the
prognosis sections listed above.
A copy of the article abstraction form is in Appendix F
Critical Appraisal Method for Treatment Articles
For each treatment article (Questions 7, 13, and 14), we abstracted data to answer the following
questions (22; 23):
•
What was the type of study?
•
What were the three most frequently occurring co-morbid conditions?
•
What were the Jadad quality scores?:
•
Randomization score ?
•
Double blind score ?
•
All patients accounted for score ?
•
Were all patients analyzed in the treatment group to which assigned?
•
Were the treatment groups similar at baseline?
•
Were the treatment groups treated equally except for the studied intervention?
•
What were the results?
18
In addition, we abstracted a number of data elements that addressed study population and
dialysis characteristics that might have affected the study results. These are the same as for the
prognosis sections listed above.
The Jadad quality scores have been empirically shown to distinguish the effect size between
reports of clinical trials. It assesses clinical trials in three domains: randomization, blinding, and
withdrawals and dropouts. Scores range from 0-5 with higher scores indicating better quality.
(24-28).
The algorithm for the Jadad quality scores is shown in Appendix G. A copy of the article
abstraction form is in Appendix F.
Evidence Synthesis
Due to sparseness of data and clinical heterogeneity among studies, we did not perform metaanalysis. Therefore, our synthesis of the evidence is qualitative.
19
RESULTS
D ISTRIBUTION
OF
EVIDENCE
The initial literature search identified 19,272 MEDLINE and 4,943 EMBASE titles. In addition,
the technical experts referred 134 articles for review, and the Sigma Tau bibliography contained
138 references not found by other means. This review yielded 24,487 titles. Of these, 22,362
titles were rejected as not meeting the inclusion criteria, leaving 2,125 titles. Of these 1,021 were
rejected at abstract screening as not meeting the inclusion criteria, thus leaving 1,104 articles. One
hundred and seventy of these were foreign language articles whose titles and abstracts were sent
to the technical experts. Of these, 102 were not selected for further evaluation, 2 were selected
but could not be translated, and 66 were further evaluated. Of the 934 English language articles,
29 were unobtainable, leaving 971 English and foreign language articles to be abstracted. Of these,
640 were rejected (R1-R6) and the remaining 331 were sent to the technical experts along with
evidence tables for these articles created from the abstraction forms. The technical experts
rejected 81 articles thus leaving 250 accepted articles entering into this evidence report (figure 1).
These articles are divided by questions and listed in Appendix E. Evidence tables for each
question are detailed in Appendix H.
20
F IGURE 1. ARTICLE S ELECTION P R O C E S S
Medline
19,272
Embase
4,943
Sigma Tau
138
Technical
Expert referrals
134
Titles reviewed
24,487
Rejected at title
stage
22,362
Selected titles,
abstracts reviewed
2,125
Foreign language
sent to technical
experts
170
Rejected
by
technical
experts
102
Unable
to
translate
2
Abstracte
d
66
Rejected at abstract
stage
1,021
Selected abstracts,
articles ordered
1,104
Articles
unavailable
29
Articles reviewed
and abstracted
971
Rejected (R1-R6)
640
Rejected by
technical experts
81
Selected articles
reviewed
by technical experts
331
Articles Accepted
250
21
Question 1: Which measure of nutritional status best predicts patient morbidity/
mortality in chronic dialysis patients?
Our literature search identified 46 studies which assessed the value of nutritional measures as
predictors of morbidity/mortality in patients on chronic dialysis. The great majority of these
studies were prospective in nature and several had follow-up of five years or more of duration.
They were evenly distributed between studies of patients on hemodialysis and peritoneal
dialysis (18 studies of hemodialysis, 15 studies peritoneal dialysis, 12 studies of both).
The best studied nutritional measure by far was serum albumin, which was reported in 35
studies. Most of these studies reported a statistically significant association between lower
serum albumin and higher mortality, and this was true for patients on hemodialysis and
peritoneal dialysis. Other nutritional prognostic factors were studied less frequently and had
less consistent results.
Details of studies are provided in Evidence Table 1.
Question 2: Which measure is the best diagnostic test for protein/ calorie
nutritional status in chronic dialysis patients?
For this study question, we identified 29 studies of which 12 were prospective cohorts, 15 were
cross-sectional assessments of diagnostic tests and nutritional status, and two had study
designs that were unclear. Both hemodialysis and peritoneal dialysis patients were studied. A
great variety of possible diagnostic tests were assessed and the reference standard for
nutritional status also varied between studies. The results were not consistent across studies.
However, some support was found for the validity of serum albumin, pre-albumin, creatinine,
protein catabolic rate (PCR), protein equivalent of total nitrogen appearance (PNA), the
subjective global nutritional assessment (SGA), anthropometric measurements, the dual x-ray
photon absorptiometry (DEXA), and transferrin.
22
Full details of the individual studies are presented in Evidence Table 2.
Question 3: What is the effect of acid/ base status on nutritional measures in
chronic dialysis patients?
Our literature search identified nine studies providing evidence relevant to this study question.
Five of these studies were randomized clinical trials, two were prospective cohort studies, one
was a clinical trial and one was a cross sectional analysis.
In a prospective, randomized, double-blind, controlled trial, Otte and colleagues (1990)
assessed the effects of a bicarbonate-based hemodialysis fluid compared with an acetatebased one in 16 patients on chronic hemodialysis. The study was cross-over in design so that
each patient served as their own control. The period of time on each dialysate was 12 weeks.
Blood chemistries were measured at the start and every 4 weeks throughout the study and the
anthropometrics were measured at the start, at 12 weeks and at the end of the study. Dietary
assessments by a dietician were performed periodically and adverse events were registered by
the nursing staff during each dialysis. Other than a slight metabolic acidosis that was more
pronounced in patients on acetate dialysis, no differences were found between groups in any of
the outcomes measured.
In a controlled trial (Graham, 1997), six patients on chronic hemodialysis were randomly
assigned in a cross-over trial to standard dialysis or dialysis with 40 mmol of bicarbonate. Oral
sodium bicarbonate was given in addition as needed to correct acidosis. Treatment resulted in
an increase in the subject’s mean bicarbonate concentration from 18.5 mmol per liter to 24.8
mmol per liter and a subsequent increase in pH from 7.36 to 7.40. While no significant
differences in anthroprometrics and body mass index were noted, radioactive leucine infusion
tests demonstrated that leucine appearance from body protein decreased significantly with
23
correction of acidosis. The authors interpreted their results as indicating that correction of
acidosis in hemodialysis is beneficial in terms of protein turn-over.
In Stein and colleagues (1997), 200 consecutive patients who were newly placed on
continuous ambulatory peritoneal dialysis were randomized in a single blinded fashion to
receive a high or a low alkali-dialysis for one year. Other measures were taken to correct
acidosis in the high alkali group. By one year of follow-up, persons randomized to the
high-alkali group had a greater increase in body weight and mid-arm circumference than those
in the low-alkali group; however, there was no difference in tricep skin fold thickness, serum
albumin or dietary protein intake. The high-alkali group had fewer hospital admissions and
spent less days in the hospital per year than the low-alkali group.
A randomized clinical trial involved 46 patients who were stable on hemodialysis (Williams,
1997). The study was single blind double crossover trial with six months during each period.
The study reported a significant improvement in triceps skin-fold thickness for patients in the
high bicarbonate dialysate compared to those in the low bicarbonate dialysate. There were no
statistically significant differences in other measures of nutrition including serum albumin
concentration, mid-arm muscle circumference, and the normalized protein catabolic rate.
In the randomized clinical trial by Brady and colleauge (1998), 36 patients who had been
stable for at least three months on hemodialysis were divided into two groups, one of whom
was dialyzed against a standard bicarbonate bath and the second group was dialyzed against a
high-alkali bicarbonate bath. The subjects randomized to the high-alkali bicarbonate bath in
addition received oral sodium bicarbonate as necessary. After 16 weeks of treatment, there
were no statistically significant differences between groups in the nutritional parameters
measured, which were serum albumin and the total lymphocyte count.
24
In a clinical trial (Harris, 1995) tested the effects of standard dialysate, a high bicarbonate
dialysate, and “modeled” bicarbonate dialysate for 4 weeks each in 9 stable adult patients on
hemodialysis. Modeled bicarbonate dialysate is a procedure where lower bicarbonate
concentrations are used early in dialysis to reduce intracellular shifting of phosphate and higher
bicarbonate is used during the last hour of dialysis to correct the acidosis, and has been
postulated to more safely improve phosphate removal. The trial was a double blind crossover trial of the three treatments with a washout period between treatments. Oral bicarbonate
therapy was given to both the high bicarbonate dialysate and the modeled bicarbonate
dialysate groups in order to maintain plasma bicarbonate concentrations at 24-26 mmol per
liter. The authors reported no difference among groups in any of the outcome measures
including measures of phosphate clearance, plasma concentration of the urea, total calcium,
blood pressure and symptoms.
The two cohort studies (Dumler, 1996 and Kang, 1997), involve 79 and 106 peritoneal dialysis
patients, respectively, and had follow-up periods of 21 months and two years. No effect of
mild acidosis was found on measures of nutritional status in either study.
In a cross-sectional analysis by Movilli and colleagues (1998), 81 patients on chronic
hemodialysis had a variety of blood chemistry and nutritional measures assessed along with
bicarbonate. The authors report a modest correlation between serum albumin level and serum
bicarbonate levels and an inverse correlation between the normalized protein catabolic rate
and increasing serum bicarbonate.
In summary, most (but not all) studies support an association between correction of acidosis
and better nutritional status.
Further details can be found in Evidence Table 3.
25
Question 4: Which levels of intake of protein and calories in chronic dialysis
patients produce the lowest morbidity/ mortality (also optimal changes in
nutritional parameters and best nitrogen balance)?
Our literature search identified 16 articles describing 15 studies that were all prospective
cohorts. Both peritoneal dialysis and hemodialysis patients were studied. Most of the studies
were small with only six studies having more than 20 patients. The length of follow-up was
anywhere from a few days to several years. In general the studies showed that increasing
dietary protein intake was associated with improvement in nutritional status measures, such as
serum albumin, pre-albumin, cholesterol, and measures of nitrogen balance.
Two studies (Kopple, 1969A & B; Archiaedo, 1990) also reported patient outcomes. In the
study of Kopple and colleagues (1969), no difference was found between patients with a lower
dietary protein intake and those with a higher dietary protein intake in terms of infection and
cardiovascular accidents. Both serum albumin and body weight increased in the patients
prescribed a high dietary protein intake. Uremic symptoms were more common in the patients
with a higher dietary protein index. In Archiaedo and colleagues (1990), 136 patients were
followed prospectively for one year. Patients were divided at baseline into five groups based
on historical data, one of which was “inadequate protein intake.” Patients on an inadequate
diet of less than 0.8 grams of protein per kilogram per day had a greater number of hospital
days per year than patients receiving an adequate diet.
In general the studies show that a dietary protein intake of 1.2 grams per kilogram per day is
necessary to avoid nitrogen imbalance.
The details of all studies are presented in Evidence Table 4.
26
Question 5: Which levels of intake of protein and calories in predialysis patients
produce the lowest morbidity at the initiation of dialysis?
Our literature search identified two meta-analyses dealing with low protein diet and patient
outcomes, and additional studies including randomized clinical trials, prospective cohorts, and
nitrogen balance studies.
The first meta-analysis (Fouque, 1992), assessed six randomized clinical trials covering 890
patients with mild-to-severe renal failure who were followed for at least one year. The
difference in protein intake between groups in a trial needed to be at least 0.2 grams of protein
per kilogram per day in order to be included. The results of this data synthesis were that
patients randomized to the low protein diet had an odds ratio of renal death of 0.54 relative to
control with a 95% confidence interval of 0.37 to 0.79.
The second meta-analysis (Pedrini, 1996), assessed the effect of low protein diets on patients
with chronic renal disease stratified by whether the renal disease was diabetic or non-diabetic
in etiology. In both strata, five randomized clinical trials were identified, comprising 1413
patients with non-diabetic renal disease and 108 patients with diabetic nephropathy. For
patients with non-diabetic renal disease, the relative risk of renal failure or death was reported
in the pooled analysis as 0.67 with a 95% confidence interval of 0.5 to 0.89. For patients with
diabetic nephropathy, a low protein diet significantly slowed the increase in the urinary
albumin level or the decline in the glomerular filtration rate with a relative risk of 0.56 and a
95% confidence interval of 0.40 to 0.77.
Therefore, the results of both meta-analyses are consistent with the hypothesis that a low
protein diet has a significant benefit in decreasing death for patients with both diabetic and nondiabetic renal disease. The results of the individual prospective cohorts and other studies were
in general agreement with the meta-analysis.
27
The details of all studies presented in Evidence Table 5.
Question 6: How does resting energy expenditure in dialysis patients compare
with resting energy expenditure in patients not on dialysis?
Our literature search identified five studies that assessed the energy expenditure of patients
using indirect calorimetry. Studies ranged in size from eight to 25 patients. Four studies
addressed patients on hemodialysis and one addressed patients on continuous ambulatory
peritoneal dialysis.
Three studies (Olevitch,1994; Schmeweiss, 1990; Montian,1986), reported no difference in
energy expenditure either between patients on hemodialysis and control patients or between
patients with chronic renal failure during periods of hemodialysis and the inter-dialytic period.
One study (Ikizler, 1996), did report a difference in energy expenditure both between chronic
hemodialysis patients and normal patients and in patients with chronic renal failure on
hemodialysis compared to the period of time between dialysis.
The one study of patients on peritoneal dialysis (Harty, 1995), reported no significant
difference in resting energy parameters between patients on peritoneal dialysis and
non-uremic control patients.
In summary, the majority of evidence indicates there is little difference in resting energy
expenditure between dialysis patients and patients not on dialysis.
Full details of all articles are presented in Evidence Table 6.
Question 7: Which nutritional interventions produce the lowest morbidity/
morality or the most optimum changes in nutritional status in dialysis patients?
Our literature search identified 18 studies relevant to this question. Nine of these were
randomized clinical trials and nine were controlled clinical trials or cohort studies. Of the nine
28
randomized clinical trials, only four had a Jadad score greater than or equal to three, a
threshold which has previously been used to characterize good quality studies. The clinical
trials studied small numbers of patients, generally between ten and thirty. A variety of oral
supplements or changes in the dialysate were assessed. Most of the studies reported mixed
results with some nutritional parameters improving and others showing no difference between
groups. A clear conclusion from these studies cannot be drawn.
The details of identified studies are reported in Evidence Table 7.
Question 8: Is interdialytic weight gain a good measure for dietary compliance or
a good prognostic indicator in dialysis patients?
Our literature search identified 12 studies relevant to this study question. These were
prospective or retrospective cohort studies, most of which had methodologic flaws. The
results of the studies were mixed. Most studies reported no correlation or only a weak
correlation between interdialytic weight gain and dietary compliance on patient outcome.
The details of all studies are reported in Evidence Table 8.
Questions 9-12: Carnitine Supplementation
Question 9: Which measure of carnitine nutritional status best predicts patient
morbidity/ mortality in chronic adult dialysis patients?
Question 10: What are the best measures of carnitine nutritional status in chronic adult
dialysis patients?
Question 11: Does carnitine supplementation in chronic adult dialysis patients improve
morbidity/ mortality?
Question 12: What are the toxic/ adverse effects of L-carnitine in adult chronic dialysis
patients?
29
Carnitine is known to be an essential co-factor in fatty acid and energy metabolism. It has also
been shown that patients on maintenance dialysis usually have low serum free L-Carnitine
concentrations and that skeletal muscle carnitine is sometimes decreased. Therefore there
have been several studies investigating the effect that replacement of L-Carnitine has on a
variety of patient outcomes, including serum triglycerides, cardiac functions and arrhythmia,
malaise asthenia, muscle cramps, weakness and fatigue, exercise capacity, and anemia.
Studies will be summarized within each of these outcomes.
Elevated Serum Triglycerides
Our literature search identified 33 studies relevant to the question of the effect of L-Carnitine
administration on elevated serum triglycerides. Ten of these were randomized clinical trials of
which eight had a Jadad score greater than or equal to three, a threshold that has been
proposed as defining “good” quality.
Of these, five studied intravenous administration or oral administration and one gave LCarnitine in the dialysite. Seven of these studies did not report any statistically significant
affect of L-Carnitine administration on triglycerides while one did report statistical
significance. Of the two other randomized clinical trials with Jadad scores less than three, one
gave L-Carnitine orally and one gave it intravenously. Both studies reported a positive effect
on triglycerides of L-Carnitine administration.
The remaining non-randomized studies reported mixed results. Details of all studies are
reported in Evidence Table 9.
In summary, data from randomized clinical trials generally do not support a beneficial effect
of L-Carnitine administration on elevated serum triglycerides in patients on maintenance
dialysis although this conclusion was not reached by all studies.
30
Cardiac Function and Arrhythmia
Our literature search identified five studies relevant to the question of the effect of L-Carnitine
administration on cardiac function and arrhythmia. Three of these were randomized clinical
trials of which 2 had a Jadad score greater than or equal to 3. Almost all of the studies
measured the cardiac outcomes differently, including dialysis-associated arrhythmia, heart
volume, ejection fraction, blood pressure and pulse rate, and measures of cardiac size.
Of the 2 best quality randomized clinical trials, neither reported a significant change in cardiac
outcomes. Details of all studies are summarized in Evidence Table 10.
In summary, there is no evidence that L-Carnitine supplementation improves cardiac
outcomes in patients on maintenance dialysis.
Malaise Asthenia, Muscle Cramps, Weakness and Fatigue
Our literature search identified six studies that provided evidence assessing the effect of LCarnitine administration on any of the symptoms malaise asthenia, muscle cramps, weakness
and fatigue occurring, either interdialytically or in the post dialysis period. Four of these were
randomized studies of which all scored greater than or equal to three on Jadad scale. Two
studies reported significant effects of carnitine supplementation and two studies did not.
Details of all studies are reported in Evidence Table 11.
In summary, there is mixed evidence regarding the effect of L-Carnitine supplementation on
improvement in symptoms of malaise asthenia, muscle cramps, weakness and fatigue in the
interdialytic and post dialectic symptoms.
31
Exercise Capacity
Our literature search identified five studies providing relevant to the question of L-Carnitine
supplementation on exercise capacity or muscle strength. Of these, three were randomized
clinical trials; all had a Jadad score greater than or equal to three.
One study (Ahmad, 1990) reported an improvement in some measures of exercise capacity
but not others. Another study (Albertazzi, 1980) reported a significant improvement in
subjective muscle strength. The last study (Fagher, 1985) reported no significant difference
between treatment and placebo arms and maximum strength or dynamic endurance.
Details of all studies are summarized in Evidence Table 12.
In summary, there is mixed evidence on the effect of L-Carnitine supplementation on
improvement in exercise capacity on patients on maintenance dialysis.
Anemia
It has been proposed that Carnitine deficiency may reduce erythrocyte half-life by adversely
influencing the integrity of the erythrocyte membrane. Our literature search identified ten
studies providing information relevant to the question of whether L-Carnitine supplementation
improves anemia or decreases erythropoietin requirements in patients on maintenance
dialysis.
Of these, five studies were randomized and four of these had a Jadad score greater than or
equal to three. Of these four studies, three reported an improvement in hemoglobin or
hematocrit and one did not.
The details of all studies are summarized in Evidence Table 13.
32
In summary, there is evidence from several small randomized trials that L-Carnitine
supplementation may improve anemia in patients on maintenance dialysis. In several of these
studies, the effect of L-Carnitine supplementation on anemia was not a primary outcome of
interest, but rather a secondary analysis and therefore these findings require confirmation in a
randomized clinical trial where treatment of anemia is the primary outcome of interest.
As our literature search did not identify convincing evidence of a benefit of carnitine
supplementation, the technical experts decided there was no need to search for evidence
regarding measurement and prognosis (Questions 9 and 10).
Regarding possible side effects of carnitine, most studies made no mention of side effects.
Four studies specifically stated no side effects occurred, one study stated there was “some
euphoria” with carnitine administration, and one study reported one patient had nausea. In
sum, there is no evidence that carnitine in standard doses is associated with serious side
effects.
Pediatrics Question 1: Which measure of nutritional status best predicts patient
morbidity/ mortality (and growth rate in children) in chronic dialysis patients?
Our literature search identified one study possibly relevant to this question. In this study (Chan,
1978) 19 pediatric patients between the ages of five and seventeen were followed
prospectively for up to 59 months. All patients were on chronic hemodialysis. The patients
were noted to be consuming far fewer calories and protein per day than recommended and
growth was in general one to four standard deviations below the mean for age.
In addition to this article there were three articles that dealt with insulin-like growth factor 1
(IGF-1). Two of these were prospective cohorts and one was a cross-sectional study. The
cross-sectional study (Besbas, 1998), reported an association between lower IGF-1 levels and
patients with malnutrition as defined by tricep skin fold thickness. However, neither of the
33
prospective cohort studies (Jasper, 1991; Hodson, 1992) identified a significant correlation
between IGF -1 levels and growth rates or nutritional parameters. In summary, there is
evidence that IGF -1 is not correlated with growth retardation in children with chronic renal
failure.
Details of the articles are listed in Evidence Table 14.
Pediatrics Question 2: Which measure is the best diagnostic test for protein/
calorie nutritional status in chronic dialysis patients?
Our literature search identified three studies relevant to this question. One study was a
retrospective cohort study, and the other two were cross sectional studies. Patients on
hemodialysis and on peritoneal dialysis were included. One study correlated skin fold
thickness and bioelectrical impedance and reported a high correlation between these two
(Stefanidis, 1996). A second study assessed the correlations between dual energy x-ray
absorptiometry, lean body mass, and urinary excretion of creatinine and reported high
correlations between all three (Cochat, 1996). A third study assessed the relation between
insulin-like growth factor 1 (IGF-1) and protein energy malnutrition as defined by
anthropometric measures in seventeen children with chronic renal failure on maintenance
hemodialysis. Transferrin and serum albumin were not correlated with anthropometric
measures while IGF-1 was significantly correlated (Besbas, 1998).
Full details of studies are presented in Evidence Table 15.
Pediatrics Question 3: What is the effect of acid/ base status on nutritional
measures in chronic dialysis patients?
We identified no studies pertaining to pediatrics and relevant to this question.
Pediatrics Question 4 and Question 5: Which levels of intake of protein and
calories in chronic dialysis produce the lowest morbidity/ mortality? Which
34
levels of intake of protein and calories in predialysis patients produce the
lowest morbidity at the initiation of dialysis?
Our literature search identified 24 studies relevant to these two questions. Sixteen of these
were prospective cohort studies. Two were retrospective cohort studies and three were cross
sectional studies. In addition there were three randomized trials of a low protein diet. Most
studies assessed either dietary energy intake or dietary protein intake on growth or nutritional
measures such as serum albumin, transferrin and cholesterol. Children on both hemodialysis
and peritoneal dialysis were studied. Follow-up times ranged from one year to as much as ten
years. Results were mixed and there was not a consistent correlation across studies between
protein and energy intake and the outcomes measured.
All three RCTs (Wingen, 1992; Kist, 1993; Uauy, 1994) of low protein diet concluded that the
low protein diet was of minimal or no value.
Full details of included studies are in Evidence Table 16.
Pediatrics Question 6: How does resting energy expenditure in dialysis patients
compare with resting energy expenditure in patients not on dialysis?
We identified no studies pertaining to pediatrics and relevant to this question.
Pediatrics Question 7: Which nutritional interventions produce the lowest
morbidity/ mortality (and best growth rate in children) or the most optimum
changes in nutritional status in dialysis patients?
We identified 11 studies relevant to this question. Of these, one was a small randomized
controlled trial that included seven patients on continuous ambulatory peritoneal dialysis and
which assessed the effect of added amino acids in the dialysate on measures of plasma,
glucose and amino-acids. The study reported that the amino-acid dialysate was less effective
than traditional glucose-containing dialysates by the standard measures of filtration. However,
the amino-acid dialysate had some significant metabolic advantages in the short-term. The
35
observational studies assessed a variety of protein and calorie supplements including aminoacid dialysates, nasal gastric tube feedings and oral supplements on a variety of outcomes
including height, weight, serum albumin, hospital admissions, catheter infections and
peritonitis. Results were mixed and findings were not consistent across studies.
Full details of these studies can be found in Evidence Table 17.
Pediatrics Question 8: Is interdialytic weight gain a good measure for dietary
compliance or a good prognostic indicator in dialysis patients?
We identified no studies pertaining to pediatrics and relevant to this question.
Pediatrics Question 13: Does growth hormone therapy improve morbidity/
mortality in pediatric chronic dialysis patients?
Our literature search identified 14 studies relevant to this study question. One of these studies
(Hokken-Koelega, 1991) was a placebo-controlled double blind cross over trial of growth
hormone treatment in pre-pubertal children with chronic renal failure. In this study, 16 children
with chronic renal failure and severe growth retardation were given biosynthetic growth
hormone at a dose of four international units per meter squared per day. Height velocity
increased in every patient during the time in every patient during the time on growth hormone.
Compared to placebo, the height velocity increase while on growth hormone was
0.9 centimeters greater per six months. This study proved that growth hormone treatment
could greatly improve height velocity in children with chronic renal failure and growth
retardation. The other studies identified in our literature search were observational and
assessed either the effects of growth hormone on different types of patients or the effect of
different levels of growth hormone. The general conclusion from these studies is that the
improvement in linear growth in patients treated with dialysis is not as great as that observed in
patients with stable chronic renal failure and that the gain in height across subsequent years is
diminished.
36
The details of all studies can be found in Evidence Table 18.
Pediatric Question 14: Does vitamin or mineral supplementation improve
morbidity/ mortality in pediatric dialysis patients? (Calcium, magnesium, and
vitamin D were not examined.)
Our literature search identified three studies relevant to this question. Two studies (Kriley,
1991; Warady, 1994) were cross-sectional examinations of dietary intake and determinations
of vitamin stores or concentrations. Both of these studies reported that the levels of many
vitamins were normal or greater than normal in both children and infants receiving peritoneal
dialysis and also on a vitamin supplementation regimen. The third study (Zlotkin, 1987)
assessed the affect of zinc absorption from glucose and amino acid dialysis solutions in
children on peritoneal dialysis. This study reported that there is a significant net absorption of
zinc from glucose containing dialysis solutions and concluded that peritoneal dialysis does not
contribute to zinc depletion.
The details of all studies can be found in Evidence Table 19.
37
SUMMARY
A large number of studies have been published in the medical literature on nutrition in dialysis
patients. Through the series of selection steps detailed above, approximately 1 in 20 of the
24,487 titles obtained from various sources was selected for data abstraction. Of these,
approximately 3% were unavailable, and two thirds were further rejected once the article was
read and evaluated in greater detail. Of the remaining 331 articles, the technical experts rejected
approximately 1 in 4, leaving 250 accepted articles.
Of these 250 accepted articles, pediatric nephrology patients were the subjects in approximately
one fourth, with adult patients being the subjects in the remaining three fourths. Of the questions
pertaining to adults, Question 9 (which measure of carnitine nutritional status best predicts
patient morbidity/mortality in chronic adult dialysis patients?) and Question 10 (what are the
best measures of carnitine nutritional status in chronic adult dialysis patients?) were not
addressed because there was insufficient evidence to conclude (for Question 11) that carnitine
supplementation in chronic adult dialysis patients improves morbidity or mortality. Of the
questions pertaining to pediatric patients, Question 3 (what is the effect of acid/base status on
nutritional measures?), Question 6 (how does resting energy expenditure in dialysis patients
compare with resting energy expenditure in patients not on dialysis?), and Question 8 (is
interdialytic weight gain a good measure for dietary compliance or a good prognostic indicator in
dialysis patients?) contained no accepted articles.
38
Question 1: Which measure of nutritional status best predicts patientmorbidity/
mortality in chronic dialysis patients?
We identified 46 studies which assessed the value of nutritional measures as predictors of
morbidity/ mortality in patients on chronic dialysis. Many articles studied albumin and
anthropometrics as prognostic factors, with other factors being less well studied. There is
consistent evidence that serum albumin is related to mortality in dialysis patients. Other
prognostic factors have been studied less frequently and/ or have had less consistent results.
Question 2: Which measure is the best diagnostic test for protein/ calorie
nutritional status in chronic dialysis patients?
Our literature search identified 29 studies pertaining to diagnostic tests for protein/ calorie
nutritional status. A consistent gold standard for the diagnosis of nutritional status in dialysis
patients was absent. Given this limitation, some support was found for the validity of serum
albumin, pre-albumin, creatinine, protein catabolic rate (PCR), protein equivalent of total
nitrogen appearance (PNA), the subjective global nutritional assessment (SGA),
anthropometric measurements, the dual x-ray photon absorptiometry (DEXA), and transferrin.
Question 3: What is the effect of acid/ base status on nutritional measures in
chronic dialysis patients?
Nine studies dealing with acid/ base status and nutrition in general supported the hypothesis
that correcting acidosis improved nutritional status.
Question 4: Which levels of intake of protein and calories in chronic dialysis
patients produce the lowest morbidity/ mortality (also optimal changes in
nutritional parameters and best nitrogen balance)
The 16 articles identified contained primarily nitrogen balance articles and in general indicate
that a dietary protein intake of 1.2g per kilogram per day is necessary to avoid nitrogen
imbalance.
39
Question 5: Which levels of intake of protein and calories in predialysis patients
produce the lowest morbidity at the initiation of dialysis?
Two meta-analyses assessing the effect of a low protein diet on predialysis patients both
reached the conclusion that such diets have a significant mortality benefit.
Question 6: How does resting energy expenditure in dialysis patients compare
with resting energy expenditure in patients not on dialysis?
The gold standard for the five articles selected was indirect calorimetry and the majority of
evidence indicates there is little difference in resting energy expenditure between dialysis
patients and patients not on dialysis.
Question 7: Which nutritional interventions produce the lowest morbidity/
morality or the most optimum changes in nutritional status in dialysis patients?
These 18 articles contained studies of both enteral and parenteral supplementation as well as
counseling. Results were inconsistent and no conclusion could be drawn.
Question 8: Is interdialytic weight gain a good measure for dietary compliance or
a good prognostic indicator in dialysis patients?
The 12 identified articles did not support a clinically important correlation between interdialytic
weight gain and dietary compliance or patient outcomes.
Questions 9-12: Carnitine Supplementation
We identified 33 studies where serum triglycerides were the outcome, five studies where
cardiac function and arrhythmia were the outcome, six studies where symptoms of malaise
asthenia, muscle cramps, weakness and fatigue were the outcome, five studies where
exercise capacity and muscle strength were the outcome, and 10 studies where anemia was
the outcome. This evidence on potential beneficial effects of carnitine is moderately extensive
but of uneven quality. Sufficient evidence to prove a benefit for carnitine was not found for
any outcome. The outcome with the best evidence of benefit was anemia. Several clinical
trials reported statistically significant improvements in hematocrit or decreases in
40
erythropoietin requirements. However, in none of these studies was the effect on anemia the
primary outcome, so these results must be viewed with caution as results of secondary
outcomes usually are known to overestimate efficacy.
There is no evidence that administration of carnitine in standard doses is associated with any
serious side effects.
Pediatrics Questions 1-14:
The evidence specific to pediatric patients was very sparce, with the exception of growth
hormone. One placebo-controlled double blind cross over trial of growth hormone in
prepubertal children with chromic renal failure provided strong evidence that growth hormone
treatment could greatly improve height velocity in such children. Other studies reported that
the improvement in linear growth in patients treated with dialysis is not as great as that
observed in patients with stable chronic renal failure and that the gain in height across
subsequent years is diminished.
41
IN-TEXT REFERENCES
1. Morbidity and mortality of dialysis. NIH Consensus Statement Online. 11(22), 1-33.
1993. 11-1-1993.
2. Komindr S, Thirawitayakom J, Taechangam S, Puchaiwatananon O, Songchisomboon S,
Domrongkitchaiporn S. Nutritional status in chronic hemodialysis patients.
Biomedical & Environmental Sciences. 1996;9:256-62.
3. Espinosa A, Cueto-Manzano AM, Velazquez-Alva C, et al. Prevalence of malnutrition in
Mexican CAPD diabetic and nondiabetic patients. Advances in Peritoneal Dialysis.
1996;12:302-6.
4. Cianciaruso B, Brunori G, Traverso G, et al. Nutritional status in the elderly patient with
uraemia. Nephrology, Dialysis, Transplantation. 1995;10 Suppl 6:65-8.
5. Kumar H, Safdar N, Naqvi SA. Nutritional assessment of patients on maintenance
haemodialysis. Journal of the Pakistan Medical Association. 1994;44:277-9.
6. Sanz A, Uson J, Alvarez R, Sancho MA, Jimenez A, Celaya S. The prevalence of
malnutrition in hemodialysis. Nutricion Hospitalaria. 1992;7:173-7.
7. Gomez P, Martinez JA, Purroy A, Larralde J. The body composition of patients
undergoing maintenance hemodialysis on an outpatient regimen. Nutricion
Hospitalaria. 1989;4:48-50.
8. Marckmann P. Nutritional status of patients on hemodialysis and peritoneal dialysis.
Clinical Nephrology. 1988;29:75-8.
9. Schoenfeld PY, Henry RR, Laird NM, Roxe DM. Assessment of nutritional status of the
National Cooperative Dialysis Study population. Kidney International Supplement. 1983;S80-S88.
10. Thunberg BJ, Swamy AP, Cestero RV. Cross-sectional and longitudinal nutritional
measurements in maintenance hemodialysis patients. American Journal of Clinical
Nutrition. 1981;34:2005-12.
11. Wolfson M, Strong CJ, Minturn D, Gray DK, Kopple JD. Nutritional status and
lymphocyte function in maintenance hemodialysis patients. American Journal of
Clinical Nutrition. 1984;39:547-55.
12. Young GA, Kopple JD, Lindholm B, et al. Nutritional assessment of continuous
ambulatory peritoneal dialysis patients: an international study. American Journal
of Kidney Diseases. 1991;17:462-71.
42
13. Nelson EE, Hong CD, Pesce AL, Peterson DW, Singh S, Pollak VE. Anthropometric norms
for the dialysis population. American Journal of Kidney Diseases. 1990;16:32-7.
14. Wolfson M. Causes, manifestations, and assessment of malnutrition in chronic renal failure.
In: Kopple JD, Massry SG, eds. Nutritional management of renal disease.
Baltimore, MD: Williams and Wilkins; 1997:245-56.
15. Cook DJ, Mulrow CD, Haynes RB. Systematic reviews: synthesis of best evidence for
clinical decisions. Ann Intern.Med. 1997;126:376-80.
16. Jadad AR, McQuay HJ. Searching the literature. Be systematic in your searching [letter].
BMJ. 1993;307:66.
17. Moher D, Fortin P, Jadad AR, et al. Completeness of reporting of trials published in
languages other than English: implications for conduct and reporting of systematic
reviews. Lancet. 1996;347:363-6.
18. Egger M, Zellweger-Zahner T, Schneider M, Junker C, Lengeler C, Antes G. Language bias
in randomised controlled trials published in English and German. Lancet.
1997;350:326-9.
19. Laupacis A, Wells G, Richardson WS, Tugwell P. Users' guides to the medical literature. V.
How to use an article about prognosis. Evidence-Based Medicine Working Group.
JAMA. 1994;272:234-7.
20. Jaeschke R, Guyatt G, Sackett DL. Users' guides to the medical literature. III. How to use
an article about a diagnostic test. A. Are the results of the study valid? EvidenceBased Medicine Working Group. JAMA. 1994;271:389-91.
21. Jaeschke R, Guyatt GH, Sackett DL. Users' guides to the medical literature. III. How to use
an article about a diagnostic test. B. What are the results and will they help me in
caring for my patients? The Evidence-Based Medicine Working Group. JAMA.
1994;271:703-7.
22. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an
article about therapy or prevention. A. Are the results of the study valid? EvidenceBased Medicine Working Group. JAMA. 1993;270:2598-601.
23. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an
article about therapy or prevention. B. What were the results and will they help me
in caring for my patients? Evidence-Based Medicine Working Group. JAMA.
1994;271:59-63.
24. Khan KS, Daya S, Jadad A. The importance of quality of primary studies in producing
unbiased systematic reviews. Arch Intern.Med. 1996;156:661-6.
43
25. Jadad AR, Rennie D. The randomized controlled trial gets a middle-aged checkup. JAMA.
1998;279:319-20.
26. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized
clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1-12.
27. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of
methodological quality associated with estimates of treatment effects in controlled
trials. JAMA. 1995;273:408-12.
28. Moher D, Jadad AR, Nichol G, Penman M, Tugwell P, Walsh S. Assessing the quality of
randomized controlled trials: an annotated bibliography of scales and checklists.
Control Clin Trials. 1995;16:62-73.
44
A PPENDIX A: G L O S S A R Y *
(Uncontrolled) before and after study
A prospective study where a cohort is determined to be the control group before an intervention,
and the same cohort is determined to be the treatment group after the intervention. Outcomes are
measured during both the control period and the treatment period and then compared. There is
not a separate group acting as concurrent controls.
Blinding (synonym: masking)
Keeping secret group assignment (e.g. to treatment or control) from the study participants or
investigators. Blinding is used to protect against the possibility that knowledge of assignment
may affect patient response to treatment, provider behaviours (performance bias) or outcome
assessment (detection bias). Blinding is not always practical (e.g. when comparing surgery to
drug treatment). The importance of blinding depends on how objective the outcome measure is;
blinding is more important for less objective outcome measures such as pain or quality of life.
See also single blind, double blind and triple blind.
Case series
An uncontrolled observational study involving an intervention and outcome for more than one
person.
Case study (synonyms: anecdote, case history, single case report)
An uncontrolled observational study involving an intervention and outcome for a single person.
* Taken primarily from The Cochrane Collaboration Handbook, Version 3.0.2 (September 1997)
46
A PPENDIX A: GLOSSARY (CONTINUED)
Case-control study (synonyms: case referent study, retrospective study)
A study that starts with identification of people with the disease or outcome of interest (cases)
and a suitable control group without the disease or outcome. The relationship of an attribute
(intervention, exposure or risk factor) to the outcome of interest is examined by comparing the
frequency or level of the attribute in the cases and controls. For example, to determine whether
thalidomide caused birth defects a group of children with birth defects (cases) could be compared
to a group of children without birth defects (controls). The groups would then be compared with
respect to the proportion exposed to thalidomide through their mothers taking the tablets. Casecontrol studies are sometimes described as being retrospective as they are always performed
looking back in time.
Clinical trial (synonyms: therapeutic trial, intervention study)
A trial that tests out a drug or other intervention to assess its effectiveness and safety. This
general term encompasses randomised controlled trials and controlled clinical trials.
Cohort study (synonyms: follow-up, incidence, longitudinal, prospective study)
An observational study in which a defined group of people (the cohort) is followed over time and
outcomes are compared in subsets of the cohort who were exposed or not exposed, or exposed at
different levels, to an intervention or other factor of interest. Cohorts can be assembled in the
present and followed into the future (a "concurrent cohort study"), or identified from past
records and followed forward from that time up to the present (a "historical cohort study").
Because random allocation is not used, matching or statistical adjustment must be used to ensure
that the comparison groups are as similar as possible.
47
A PPENDIX A: GLOSSARY (CONTINUED)
Control
1. In clinical trials comparing two or more interventions, a control is a person in the
comparison group that receives a placebo, no intervention, usual care or another form
of care.
2. In case-control studies a control is a person in the comparison group without the disease
or outcome of interest.
3. In statistics control means to adjust for or take into account extraneous influences or
observations.
4. Control can also mean programs aimed at reducing or eliminating the disease when
applied to communicable (infectious) diseases.
Controlled clinical trial
Refers to a study that compares one or more intervention groups to one or more comparison
(control) groups. Whilst not all controlled studies are randomised, all randomised trials are
controlled.
Cross-sectional study (synonym: prevalence study)
A study that examines the relationship between diseases (or other health related characteristics)
and other variables of interest as they exist in a defined population at one particular time. The
temporal sequence of cause and effect cannot necessarily be determined in a cross-sectional
study.
Cross-over trial
A type of clinical trial comparing two or more interventions in which the participants, upon
completion of the course of one treatment are switched to another. For example, for a
48
A PPENDIX A: GLOSSARY (CONTINUED)
comparison of treatments A and B, half the participants are randomly allocated to receive them in
the order A, B and half to receive them in the order B, A. A problem with this design is that the
effects of the first treatment may carry over into the period when the second is given.
Double blind (synonym: double masked)
Neither the participants in a trial nor the investigators (outcome assessors) are aware of which
intervention the participants are given. The purpose of blinding the participants (recipients and
providers of care) is to prevent performance bias. The purpose of blinding the investigators
(outcome assessors, who might also be the care providers) is to protect against detection bias.
See also blinding, single blind, triple blind, concealment of allocation.
EMBASE (Excerpta Medica database)
A European-based electronic database of pharmacological and biomedical literature covering 3,500
journals from 110 countries. Years of coverage - 1974 to present.
Gold standard
The method, procedure or measurement that is widely accepted as being the best available against
which new interventions should be compared. It is particularly important in studies of the
accuracy of diagnostic tests. For example, handsearching is sometimes used as the gold standard
for identifying trials against which electronic searches of databases such as MEDLINE are
compared.
49
A PPENDIX A: GLOSSARY (CONTINUED)
Historical control
Person or group for whom data were collected earlier than for the group being studied. Because
of changes over time in risks, prognosis, healthcare, etc. there is a large risk of bias (in studies that
use historical controls) due to systematic differences between the comparison groups.
Intention-to-treat
An intention-to-treat analysis is one in which all the participants in a trial are analyzed according
to the intervention to which they were allocated, whether they received it or not. Intention-totreat analyzes are favoured in assessments of effectiveness as they mirror the non-compliance
and treatment changes that are likely to occur when the intervention is used in practice, and
because of the risk of attrition bias when participants are excluded from the analysis.
MEDLINE (MEDlars onLINE)
An electronic database produced by the United States National Library of Medicine. It indexes
millions of articles in selected (about 3,700) journals. It is available through most medical
libraries, and can be accessed on CD-ROM, the Internet and by other means. Years of coverage 1966 to present.
Methodological quality (synonyms: validity, internal validity)
The extent to which the design and conduct of a trial are likely to have prevented systematic
errors (bias). Variation in quality can explain variation in the results of trials included in a
systematic review. More rigorously designed (better 'quality') trials are more likely to yield
results that are closer to the 'truth'. See also external validity, validity.
50
A PPENDIX A: GLOSSARY (CONTINUED)
Observational study (synonym: non-experimental study)
A study in which nature is allowed to take its course. Changes or differences in one characteristic
(e.g. whether or not people received the intervention of interest) are studied in relation to changes
or differences in other(s) (e.g. whether or not they died), without the intervention of the
investigator. There is a greater risk of selection bias than in experimental studies (randomised
controlled trials).
Odds ratio (OR)
The ratio of the odds of an event in the experimental (intervention) group to the odds of an event
in the control group. Odds are the ratio of the number of people in a group with an event to the
number without an event. Thus, if a group of 100 people had an event rate of 0.20, 20 people
had the event and 80 did not, and the odds would be 20/80 or 0.25. An odds ratio of one
indicates no difference between comparison groups. For undesirable outcomes an OR that is less
than one indicates that the intervention was effective in reducing the risk of that outcome. When
the event rate is small, odds ratios are very similar to relative risks.
Per protocol analysis
Analysis performed where only patients remaining in the study at study conclusion are
analyzed.
Placebo
An inactive substance or procedure administered to a patient, usually to compare its effects with
those of a real drug or other intervention, but sometimes for the psychological benefit to the
patient through a belief that s/he is receiving treatment. Placebos are used in clinical trials to
51
A PPENDIX A: GLOSSARY (CONTINUED)
blind people to their treatment allocation. Placebos should be indistinguishable from the active
intervention to ensure adequate blinding.
Prospective
study
In evaluations of the effects of healthcare interventions, a study in which people are divided into
groups that are exposed or not exposed to the intervention(s) of interest before the outcomes
have occurred. Randomised controlled trials are always prospective studies and case control
studies never are. Concurrent cohort studies are prospective studies, whereas historical cohort
studies are not (see cohort study), although in epidemiology a prospective study is sometimes
used as a synonym for cohort study. See retrospective study.
P-value
The probability (ranging from zero to one) that the observed results in a study, or results more
extreme, could have occurred by chance. In a meta-analysis the P-value for the overall effect
assesses the overall statistical significance of the difference between the treatment and control
groups, whilst the P-value for the heterogeneity statistic assesses the statistical significance of
differences between the effects observed in each study.
Quality score
A value assigned to represent the validity of a study either for a specific criterion, such as
allocation concealment, or overall. Quality scores can be use letters (A, B, C) or numbers. An
advantage of using letters is that the order of best to worst may be more obvious than for
numbers.
52
A PPENDIX A: GLOSSARY (CONTINUED)
Quasi-random allocation
A method of allocating participants to different forms of care that is not truly random; for
example, allocation by date of birth, day of the week, medical record number, month of the year,
or the order in which participants are included in the study (e.g. alternation).
Random allocation
A method that uses the play of chance to assign participants to comparison groups in a trial, e.g.
by using a random numbers table or a computer-generated random sequence. Random allocation
implies that each individual or unit being entered into a trial has the same chance of receiving each
of the possible interventions. It also implies that the probability that an individual will receive a
particular intervention is independent of the probability that any other individual will receive the
same intervention. See also concealment of allocation, quasi-random allocation, randomization.
Randomization
Method used to generate a random allocation sequence, such as using tables of random numbers
or computer-generated random sequences. The method of randomization should be distinguished
from concealment of allocation because of the risk of selection bias despite the use of
randomization, if there is not adequate allocation concealment. For instance, a list of random
numbers may be used to randomize participants, but if the list is open to the individuals
responsible for recruiting and allocating participants, those individuals can influence the allocation
process, either knowingly or unknowingly.
53
A PPENDIX A: GLOSSARY (CONTINUED)
Randomized control trial (RCT) (synonym: randomized clinical trial)
An experiment in which investigators randomly allocate eligible people into (e.g. treatment and
control) groups to receive or not to receive one or more interventions that are being compared.
The results are assessed by comparing outcomes in the treatment and control groups. NOTE:
when using randomized controlled trial as a search term (publication type) in MEDLINE, the US
spelling (randomized) must be used.
Relative Risk (RR) (synonym: risk ratio)
The ratio of risk in the intervention group to the risk in the control group. The risk (proportion,
probability or rate) is the ratio of people with an event in a group to the total in the group. A
relative risk of one indicates no difference between comparison groups. A relative risk of one
indicates no difference between comparison groups. For undesirable outcomes a RR that is less
than one indicates that the intervention was effective in reducing the risk of that outcome.
Retrospective
study
A study in which the outcomes have occurred to the participants before the study commenced.
Case control studies are always retrospective, cohort studies sometimes are, randomized
controlled trials never are. See prospective study.
Statistical significance
An estimate of the probability of an association (effect) as large or larger than what is observed in
a study occurring by chance, usually expressed as a P-value. For example, a P-value of 0.049 for
a risk difference of 10% means that there is less than a one in 20 (0.05) chance of an association
that is as large or larger having occurred by chance and it could be said that the results are
54
A PPENDIX A: GLOSSARY (CONTINUED)
"statistically significant" at P = 0.05). The cut-off for statistical significance is usually taken at
0.05, but sometimes at 0.01 or 0.10. These cut-offs are arbitrary and have no specific
importance. Although it is often done, it is inappropriate to interpret the results of a study
differently according to whether the P-value is, say, 0.055 or 0.045 (which are quite similar
values, not diametrically opposed ones).
Washout period
The stage in a cross-over trial when treatment is withdrawn before the second treatment is given.
Washout periods are usually necessary because of the possibility that the intervention
administered first can affect the outcome variable for some time after treatment ceases. A run-in
period before a trial starts is sometimes called a washout period if treatments that participants
were using before entering the trial are discontinued.
55
A PPENDIX B: TECHNICAL E XPERTS - NKF DOQI N UTRITION
W ORKGROUP
IN
D IALYSIS
ADULT T ECHNICAL EXPERTS
Joel D. Kopple, M.D.
Professor of Medicine and Public Health
University of California, Los Angeles
Schools of Medicine and Public Health
Chief, Division of Nephrology and
Hypertension
Harbor-UCLA Medical Center
Torrance, California
Charles Foulks, M.D., F.A.C.P.
Professor of Medicine
Director
Division of Nephrology and Hypertension
Texas A&M University Center for the
Health Sciences
Scott & White Clinic
Temple, TX
Suhail Ahmad, M.B.,B.S.
Associate Professor, Medicine
Medical Director,
Dialysis & Apheresis Lab.
University of Washington,
Medical Director,
Scribner Kidney Center,
Seattle
Denis Fouque, MD,PhD
Professor of Nephrology
Director, Cochrane Renal Group
Hospital Edouard Herriot
University Claude Bernard Lyon1
France
Bradley J. Maroni, M.D.
Associate Medical Director
AMGEN, Inc.
Thousand Oaks, CA
Jerrilynn Burrowes, MS, RD, CS
Research Coordinator
Division of Nephrology & Hypertension.
Beth Israel Medical Center
New York
Linda W. Moore, RD
Sr.Manager, Scientific Publications
SangStat Medical Corporation
Germantown, TN 38138
Glenn M. Chertow, MD, MPH, CNSP
Director of Clinical Services
Divisions of Nephrology
Moffitt-Long Hospitals and UCSF-Mt. Zion
Medical Center
Assistant Professor of Medicine in
Residence
University of California, San Francisco
Marsha Wolfson, M.D.
Medical Director, Renal Division
Baxter Healthcare Corporation
McGaw Park, IL
David Cochram, M.S., R.D.
Clinical Research Scientist
Medical and Scientific Affairs
Ross Products Division
Abbott Laboratories
Columbus, OH
56
APPENDIX B: TECHNICAL EXPERTS - NKF DOQI NUTRITION IN DIALYSIS W ORKGROUP
(CONTINUED)
PEDIATRIC T ECHNICAL EXPERTS
Bruce Morgenstern, M.D.
Associate Professor of Pediatrics
Mayo Medical School
Consultant in Pediatric Nephrology
Mayo Clinic
Rochester, MN
Isidro B. Salusky, M.D.
Professor of Pediatrics
Director, Pediatric Dialysis Program
Director, General Clinical Research Center
UCLA School of Medicine
James Chan, M.D.
Professor of Pediatrics
Chair, Division of Pediatric Nephrology
Vice Chair, Department of Pediatrics
Medical College of Virginia
Richmond
Pauline Nelson, R.D.
Pediatric Renal Dietitian
Department of Nutrition
UCLA Medical Center
Los Angeles
Bradley A. Warady M.D.
Professor of Pediatrics
University of Missouri - Kansas City
School of Medicine
Chief, Section of Pediatric Nephrology
Director, Dialysis and Transplantation
The Childrens Mercy Hospital
Richard Fine, M.D.
Professor and Chairman
Department of Pediatrics
SUNY at Stonybrook School of Medicine
Craig B. Langman, M.D.
Professor of Pediatrics
Northwestern University School of
Medicine
Head, Nephrology and Mineral Metabolism
Children's Memorial Medical Center
Chicago
57
A PPENDIX C: SEARCH S T R A T E G I E S
Strategies for Questions 1-8
#1965-April, 1998
1) hemodialysis/
2) hemodiafiltration/
3) hemodialysis, home/
4) hemofiltration/
5) hemodiafiltration/
6) peritoneal dialysis/
7) peritoneal dialysis, continuous ambulatory/
8) 1 or 2 or 3 or 4 or 5 or 6 or 7
9) kidney, artificial/
10) dialysis/
11) 9 or 10
12) kidney failure, chronic/
13) 8 or 11
14) renal replacement therapy/
15) 8 or 11 or 12 or 14
16) 8 or 12 or 14
17) nutrition assessment/
18) nutrition surveys/
19) diet surveys/
20) 17 or 18 or 19
21) nutrition/
22) diet/
23) energy intake/
24) nutritional requirements/
25) nutritional status/
26) 21 or 22 or 23 or 24 or 25
27) nutrition disorders/
28) protein deficiency/
29) protein-energy malnutrition/
30) 27 or 28 or 29
31) caloric intake/
32) exp dietary proteins/
33) nutrition$.tw.
34) protein$.tw.
35) calori$.tw.
36) dh.fs.
37) exp diet therapy/
58
39)
40)
41)
42)
43)
44)
45)
46)
47)
48)
49)
50)
51)
52)
53)
54)
55)
56)
57)
58)
59)
60)
61)
62)
63)
64)
65)
66)
67)
68)
69)
70)
71)
72)
73)
74)
75)
skinfold thickness/
anthropometry/
body mass index/
body height/
body surface area/
body weight/
creatinine/
cholesterol/
exp proteins/
kidney function tests/
blood urea nitrogen/
diet records/
subjective global assessment.tw.
acute phase protein.tw.
prognos$.tw.
prognosis/
npna.tw.
npcr.tw.
pcr.tw.
pna.tw.
protein catabolic rate.tw.
(protein adj4 nitrogen appearance).tw.
body water/
electric impedance/
or/39-62
predialysis.tw.
energy expenditure.tw.
resting energy.tw.
exp energy metabolism/
nitrogen/
nitrogen.tw.
reference values/
reference standards/
dh.fs.
intradialytic.tw.
diet therapy/
diet, protein-restricted/
APPENDIX C: SEARCH STRATEGIES (CONTINUED)
38) 20 or 26 or 30 or 31 or 32 or 33 or 34 or 35
or 36 or 37
59
76) nutritional support/
APPENDIX C: SEARCH STRATEGIES (CONTINUED)
Strategies for Questions 1-8 (continued)
77) enteral nutrition/
78) parenteral nutrition/
79) parenteral nutrition, home/
80) parenteral nutrition, home total/
81) parenteral nutrition, total/
82) parenteral nutrition, home total/
83) (nutrition$ adj4 counsel$).ti,ab,sh.
84) (oral adj4 supplement$).tw.
85) tube feeding/
86) food, formulated/
87) or/64-86
88) health education/
89) patient education/
90) patient education.tw.
91) counsel$.tw.
92) or/88-91
93) 38 or 63 or 87
94) 16 and 93
95) 8 and 92
96) 94 or 95
97) 96 not letter.pt.
98) 97 not editorial.pt.
99) 98 not news.pt.
100) 99 not case report/
101) 100 not animal/
102) limit 100 to human
103) 101 or 102
60
APPENDIX C: SEARCH STRATEGIES (CONTINUED)
Search strategy for Questions 9-12
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
12)
13)
14)
15)
16)
17)
18)
19)
20)
21)
22)
23)
24)
25)
26)
27)
28)
29)
30)
31)
hemodialysis/
hemodiafiltration/
hemodialysis, home/
hemofiltration/
hemodiafiltration/
peritoneal dialysis/
peritoneal dialysis, continuous ambulatory/
1 or 2 or 3 or 4 or 5 or 6 or 7
kidney, artificial/
dialysis/
9 or 10
kidney failure, chronic/
8 or 11
8 or 11 or 12
carnitine/
acetylcarnitine/
palmitoylcarnitine/
15 or 16 or 17
541-15-1.rn.
1935-18-8.rn.
14992-62-2.rn.
l-carnitine.tw.
carnitine.tw.
bicarnesine.tw.
vitamin bt.tw.
vitamin b t.tw.
or/18-26
8 and 27
14 and 27
29 not letter.pt.
30 not news.pt.
61
APPENDIX C: SEARCH STRATEGIES (CONTINUED)
Search strategy for Question 13 , 14 and IGF (Pediatric Question 1)
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
12)
13)
14)
15)
16)
17)
18)
19)
20)
21)
22)
23)
24)
25)
26)
27)
28)
29)
30)
31)
32)
33)
34)
renal replacement therapy/
hemodialysis/
hemodiafiltration/
hemodialysis, home/
hemofiltration/
hemodiafiltration/
peritoneal dialysis/
peritoneal dialysis, continuous ambulatory/
1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
limit 9 to (newborn infant <birth to 1 month> or infant <1 to 23 months> or preschool
child <2 to 5 years> or child <6 to 12 years> or adolescence <13 to 18 years>)
10 not letter.pt.
11 not review.pt.
12 not editorial.pt.
13 not case report/
insulin-like growth factor i/
somatomedins/
14 and 15
14 and 16
14 and igf.tw.
14 and insulin like growth.tw.
or/17-20
exp minerals/
14 and 22
vitamins/
ascorbic acid/
bioflavonoids/
vitamin a/
vitamin b complex/
vitamin e/
vitamin k/
vitamin u/
24 or 25 or 26 or 27 or 28 or 29 or 30 or 31
14 and 32
23 or 33
62
A PPENDIX D: B IBLIOGRAPHY
OF
A CCEPTED
ARTICLES *
References for Questions 1-12 - Adults
Question 1 - adults
1. Acchiardo SR, Moore LW, Latour PA. Malnutrition as the main factor in morbidity and
mortality of hemodialysis patients. Kidney International - Supplement. 1983;16:S199S203.
Reference ID: 12089
2. Avram MM, Goldwasser P, Erroa M, Fein PA. Predictors of survival in continuous
ambulatory peritoneal dialysis patients: the importance of prealbumin and other nutritional
and metabolic markers. American Journal of Kidney Diseases. 1994;23:91-8.
Reference ID: 3778
3. Avram MM, Mittman N, Bonomini L, Chattopadhyay J, Fein P. Markers for survival in
dialysis: A seven-year prospective study. American Journal of Kidney Diseases.
1995;26:209-19.
Reference ID: 2672
4. Avram MM, Fein PA, Bonomini L, et al. Predictors of survival in continuous ambulatory
peritoneal dialysis patients: a five-year prospective study. Peritoneal Dialysis
International. 1996;16 Suppl 1:S190-S194.
Reference ID: 1975
5. Barrett BJ, Parfrey PS, Morgan J, et al. Prediction of early death in end-stage renal disease
patients starting dialysis. American Journal of Kidney Diseases. 1997;29:214-22.
Reference ID: 789
6. Bilbrey GL, Cohen TL. Identification and treatment of protein calorie malnutrition in
chronic hemodialysis patients. Dialysis Transplant. 1989;18:669-77+700.
Reference ID: 4907
7. Blake PG, Sombolos K, Abraham G, et al. Lack of correlation between urea kinetic indices
and clinical outcomes in CAPD patients [published erratum appears in Kidney Int 1991
Aug;40(2):388]. Kidney International. 1991;39:700-6.
Reference ID: 6826
8. Blake PG, Flowerdew G, Blake RM, Oreopoulos DG. Serum albumin in patients on
continuous ambulatory peritoneal dialysis--predictors and correlations with outcomes.
Journal of the American Society of Nephrology. 1993;3:1501-7.
Reference ID: 4841
* Reference ID numbers correspond with those listed in the evidence tables.
63
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
9. Canaud B, Garred LJ, Argiles A, Flavier JL, Bouloux C, Mion C. Creatinine kinetic
modelling: a simple and reliable tool for the assessment of protein nutritional status in
haemodialysis patients. Nephrology, Dialysis, Transplantation. 1995;10:1405-10.
Reference ID: 2921
10. Chertow, G. M., Jacobs, D. O., Lazarus, J. M., Lew, N. L., and Lowrie, E. G. Phase angle
predicts survival in hemodialysis patients. Journal of Renal Nutrition 7(4), 204-207. 1997.
(GENERIC)
Reference ID: 18834
11. Churchill DN, Taylor DW, Cook RJ, et al. Canadian hemodialysis morbidity study.
Am.J.Kidney Dis. 1992;19:214-34.
Reference ID: 4884
12. Churchill DN, Taylor DW, Keshaviah PR, et al. Adequacy of dialysis and nutrition in
continuous peritoneal dialysis: Association with clinical outcomes. Journal of the American
Society of Nephrology. 1996;7:198-207.
Reference ID: 5129
13. Churchill DN, Thorpe KE, Vonesh EF, Keshaviah PR. Lower probability of patient
survival and continuous peritoneal dialysis in the United States compared with Canada.
Journal of the American Society of Nephrology. 1997;8:965-71.
Reference ID: 5076
14. Davies SJ, Phillips L, Russell GI. Peritoneal solute transport predicts survival on CAPD
independently of residual renal function. Nephrology Dialysis Transplantation.
1998;13:962-8.
Reference ID: 5038
15. De Lima J, Sesso R, Abensur H, et al. Predictors of mortality in long-term haemodialysis
patients with a low prevalence of comorbid conditions. Nephrology, Dialysis,
Transplantation. 1995;10:1708-13.
Reference ID: 2455
16. Degoulet P, Legrain M, Reach I, et al. Mortality risk factors in patients treated by chronic
hemodialysis. Report of the Diaphane collaborative study. Nephron. 1982;31:103-10.
Reference ID: 12751
17. Fenton SS, Johnston N, Delmore T, et al. Nutritional assessment of continuous ambulatory
peritoneal dialysis patients. ASAIO Transactions. 1987;33:650-3.
Reference ID: 9955
64
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
18. Fine A, Cox D. Modest reduction of serum albumin in continuous ambulatory peritoneal
dialysis patients is common and of no apparent clinical consequence [see comments].
American Journal of Kidney Diseases. 1992;20:50-4.
Reference ID: 5722
19. Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. Hypoalbuminemia,
cardiac morbidity, and mortality in end-stage renal disease. Journal of the American Society
of Nephrology. 1996;7:728-36.
Reference ID: 1576
20. Fried L, Bernardini J, Piraino B. Neither size nor weight predicts survival in peritoneal
dialysis patients. Peritoneal Dialysis International. 1996;16:357-61.
Reference ID: 1203
21. Goldwasser P, Michel MA, Collier J, et al. Prealbumin and lipoprotein(a) in hemodialysis:
relationships with patient and vascular access survival. American Journal of Kidney
Diseases. 1993;22:215-25.
Reference ID: 4753
22. Goldwasser P, Mittman N, Antignani A, et al. Predictors of mortality in hemodialysis
patients. Journal of the American Society of Nephrology. 1993;3:1613-22.
Reference ID: 4686
23. Himmelfarb J, Holbrook D, McMonagle E, Robinson R, Nye L, Spratt D. Kt/V, nutritional
parameters, serum cortisol, and insulin growth factor-1 levels and patient outcome in
hemodialysis. American Journal of Kidney Diseases. 1994;24:473-9.
Reference ID: 3628
24. Husebye DG, Westlie L, Styrvoky TJ, Kjellstrand CM. Psychological, social, and somatic
prognostic indicators in old patients undergoing long-term dialysis. Archives of Internal
Medicine. 1987;147:1921-4.
Reference ID: 9917
25. Ifudu O, Paul HR, Homel P, Friedman EA. Predictive value of functional status for
mortality in patients on maintenance hemodialysis. American Journal of Nephrology.
1998;18:109-16.
Reference ID: 5037
26. Iseki K, Uehara H, Nishime K, et al. Impact of the initial levels of laboratory variables on
survival in chronic dialysis patients. American Journal of Kidney Diseases. 1996;28:541-8.
Reference ID: 1523
65
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
27. Iseki K, Miyasato F, Tokuyama K, et al. Low diastolic blood pressure, hypoalbuminemia,
and risk of death in a cohort of chronic hemodialysis patients. Kidney International.
1997;51:1212-7.
Reference ID: 863
28. Jassal SV, Douglas JF, Stout RW. Prognostic markers in older patients starting renal
replacement therapy. Nephrology, Dialysis, Transplantation. 1996;11:1052-7.
Reference ID: 1657
29. Lowrie EG, Huang WH, Lew NL. Death risk predictors among peritoneal dialysis and
hemodialysis patients: A preliminary comparison. American Journal of Kidney Diseases.
1995;26:220-8.
Reference ID: 5157
30. Maggiore Q, Nigrelli S, Ciccarelli C, Grimaldi C, Rossi GA, Michelassi C. Nutritional and
prognostic correlates of bioimpedance indexes in hemodialysis patients. Kidney
International. 1996;50:2103-8.
Reference ID: 1277
31. Maiorca R, Brunori G, Zubani R, et al. Predictive value of dialysis adequacy and nutritional
indices for mortality and morbidity in CAPD and HD patients. A longitudinal study.
Nephrology, Dialysis, Transplantation. 1995;10:2295-305.
Reference ID: 2371
32. Marcen R, Teruel JL, de lA, Gamez C. The impact of malnutrition in morbidity and
mortality in stable haemodialysis patients. Spanish Cooperative Study of Nutrition in
Hemodialysis [see comments]. Nephrology, Dialysis, Transplantation. 1997;12:2324-31.
Reference ID: 173
33. Movilli E, Mombelloni S, Gaggiotti M, Maiorca R. Effect of age on protein catabolic rate,
morbidity, and mortality in uraemic patients with adequate dialysis.
Nephrol.Dial.Transplant. 1993;8:735-9.
Reference ID: 4867
34. Movilli E, Filippini M, Brunori G, et al. Influence of protein catabolic rate on nutritional
status, morbidity and mortality in elderly uraemic patients on chronic haemodialysis: a
prospective 3-year follow-up study. Nephrology, Dialysis, Transplantation. 1995;10:5148.
Reference ID: 2946
35. Oksa H, Pasternack A, Pasanen M. Serum urea-creatinine ratio as a prognostic index in
hemodialysis patients. Clinical Nephrology. 1987;27:125-30.
Reference ID: 9936
66
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
36. Owen WF, Jr., Lew NL, Liu Y, Lowrie EG, Lazarus JM. The urea reduction ratio and
serum albumin concentration as predictors of mortality in patients undergoing
hemodialysis. New Engl.J.Med. 1993;329:1001-6.
Reference ID: 4857
37. Piccoli GB, Quarello F, Salomone M, et al. Are serum albumin and cholesterol reliable
outcome markers in elderly dialysis patients?. Nephrology, Dialysis, Transplantation.
1995;10 Suppl 6:72-7.
Reference ID: 2911
38. Piraino B, Bernardini J, Centa PK, Johnston JR, Sorkin MI. The effect of body weight on
CAPD related infections and catheter loss. Peritoneal Dialysis International. 1991;11:64-8.
Reference ID: 6916
39. Pollock CA, Ibels LS, Allen BJ, et al. Total body nitrogen as a prognostic marker in
maintenance dialysis. Journal of the American Society of Nephrology. 1995;6:82-8.
Reference ID: 2690
40. Soucie JM, McClellan WM. Early death in dialysis patients: risk factors and impact on
incidence and mortality rates. Journal of the American Society of Nephrology.
1996;7:2169-75.
Reference ID: 1075
41. Spiegel DM, Breyer JA. Serum albumin: a predictor of long-term outcome in peritoneal
dialysis patients. American Journal of Kidney Diseases. 1994;23:283-5.
Reference ID: 3835
42. Sreedhara R, Avram MM, Blanco M, Batish R, Mittman N. Prealbumin is the best
nutritional predictor of survival in hemodialysis and peritoneal dialysis. American Journal
of Kidney Diseases. 1996;28:937-42.
Reference ID: 1240
43. Struijk DG, Krediet RT, Koomen GC, Boeschoten EW, Arisz L. The effect of serum
albumin at the start of continuous ambulatory peritoneal dialysis treatment on patient
survival [see comments]. Peritoneal Dialysis International. 1994;14:121-6.
Reference ID: 4052
44. Teehan BP, Schleifer CR, Brown JM, Sigler MH, Raimondo J. Urea kinetic analysis and
clinical outcome on CAPD. A five year longitudinal study. Advances in Peritoneal
Dialysis. 1990;6:181-5.
Reference ID: 7051
Question 2 - adults
67
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
1. Bilbrey GL, Cohen TL. Identification and treatment of protein calorie malnutrition in
chronic hemodialysis patients. Dialysis Transplant. 1989;18:669-77+700.
Reference ID: 4907
2. Borovnicar DJ, Wong KC, Kerr PG, et al. Total body protein status assessed by different
estimates of fat-free mass in adult peritoneal dialysis patients. European Journal of Clinical
Nutrition. 1996;50:607-16.
Reference ID: 1031
3. Chauveau P, Naret C, Puget J, Zins B, Poignet JL. Adequacy of haemodialysis and
nutrition in maintenance haemodialysis patients: clinical evaluation of a new on-line urea
monitor. Nephrology, Dialysis, Transplantation. 1996;11:1568-73.
Reference ID: 1335
4. Chertow GM, Lowrie EG, Wilmore DW, et al. Nutritional assessment with bioelectrical
impedance analysis in maintenance hemodialysis patients. Journal of the American Society
of Nephrology. 1995;6:75-81.
Reference ID: 2689
5. Chertow GM, Lazarus JM, Lew NL, Ma L, Lowrie EG. Bioimpedance norms for the
hemodialysis population. Kidney International. 1997;52:1617-21.
Reference ID: 313
6. Cueto-Manzano AM, Espinosa A, Hernandez A, Correa-Rotter R. Peritoneal transport
kinetics correlate with serum albumin but not with the overall nutritional status in CAPD
patients. American Journal of Kidney Diseases. 1997;30:229-36.
Reference ID: 815
7. De Fijter M, De FW, Oe PL, ter WM, Donker AJ. Assessment of total body water and
lean body mass from anthropometry, Watson formula, creatinine kinetics, and body
electrical impedance compared with antipyrine kinetics in peritoneal dialysis patients.
Nephrology, Dialysis, Transplantation. 1997;12:151-6.
Reference ID: 248
8. Formica C, Atkinson MG, Nyulasi I, McKay J, Heale W, Seeman E. Body composition
following hemodialysis: Studies using dual-energy X-ray absorptiometry and bioelectrical
impedance analysis. Osteoporosis Int. 1993;3:192-7.
Reference ID: 4869
9. Han DS, Lee SW, Kang SW, et al. Factors affecting low values of serum albumin in CAPD
patients. Advances in Peritoneal Dialysis. 1996;12:288-92.
Reference ID: 1373
68
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
10. Harrison JE, McNeill KG, Strauss AL. A nitrogen index - total body protein normalized for
body size - for diagnosis of protein status in health and disease. Nutr.Res. 1984;4:209-24.
Reference ID: 4959
11. Harty JC, Boulton H, Curwell J, et al. The normalized protein catabolic rate is a flawed
marker of nutrition in CAPD patients. Kidney International. 1994;45:103-9.
Reference ID: 3810
12. Jacob V, Marchant PR, Wild G, Brown CB, Moorhead PJ, el NM. Nutritional profile of
continuous ambulatory peritoneal dialysis patients. Nephron. 1995;71:16-22.
Reference ID: 2966
13. Johansson AC, Attman PO, Haraldsson B. Creatinine generation rate and lean body mass: a
critical analysis in peritoneal dialysis patients. Kidney International. 1997;51:855-9.
Reference ID: 635
14. Jones CH, Newstead CG, Will EJ, Smye SW, Davison AM. Assessment of nutritional
status in CAPD patients: serum albumin is not a useful measure. Nephrology, Dialysis,
Transplantation. 1997;12:1406-13.
Reference ID: 733
15. Kawaguchi Y, Sugino N, Arai J, et al. Nutritional assessment of patients on continuous
ambulatory peritoneal dialysis. Nippon Jinzo Gakkai Shi.Japanese Journal of Nephrology.
1993;35:843-51.
Reference ID: 4315
16. Kuhlmann MK, Winkelspecht B, Hammers A, Kohler H. [Malnutrition in hemodialysis
patients. Self-assessment, medical evaluation and "verifiable" parameters]. [German].
Medizinische Klinik. 1997;92:13-7.
Reference ID: 242
17. Lorenzo V, de BE, Rufino M, et al. Caloric rather than protein deficiency predominates in
stable chronic haemodialysis patients. Nephrology, Dialysis, Transplantation.
1995;10:1885-9.
Reference ID: 2193
18. Madore F, Wuest M, Ethier JH. Nutritional evaluation of hemodialysis patients using an
impedance index. Clinical Nephrology. 1994;41:377-82.
Reference ID: 3278
19. Oe B, De Fijter CWH, Oe PL, Stevens P, De Vries PMJ. Four-site skinfold anthropometry
(FSA) versus body impedance analysis (BIA) in assessing nutritional status of patients on
maintenance hemodialysis: Which method is to be preferred in routine patient care. Clinical
Nephrology. 1998;49:180-5.
Reference ID: 5043
69
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
20. Oksa H, Ahonen K, Pasternack A, Marnela KM. Malnutrition in hemodialysis patients.
Scandinavian Journal of Urology & Nephrology. 1991;25:157-61.
Reference ID: 6603
21. Panzetta G, Tessitore N, Faccini G, Maschio G. The protein catabolic rate as a measure of
protein intake in dialysis patients: usefulness and limits. Nephrology, Dialysis,
Transplantation. 1990;5 Suppl 1:125-7.
Reference ID: 7096
22. Pollock CA, Allen BJ, Warden RA, et al. Total-body nitrogen by neutron activation in
maintenance dialysis [published erratum appears in Am J Kidney Dis 1993 Feb;21(2):237].
Reference ID: 6975
23. Rayner HC, Stroud DB, Salamon KM, et al. Anthropometry underestimates body protein
depletion in haemodialysis patients. Nephron. 1991;59:33-40.
Reference ID: 6582
24. Schmidt R, Dumler F, Cruz C, Lubkowski T, Kilates C. Improved nutritional follow-up of
peritoneal dialysis patients with bioelectrical impedance. Advances in Peritoneal Dialysis.
1992;8:157-9.
Reference ID: 5421
25. Sombolos K, Berkelhammer C, Baker J. Nutritional assessment and skeletal muscle function
in patients on continuous ambulatory peritoneal dialysis. Peritoneal Dial.Bull. 1986;6:53-8.
Reference ID: 4938
26. Stall SH, Ginsberg NS, DeVita MV, et al. Comparison of five body-composition methods
in peritoneal dialysis patients. American Journal of Clinical Nutrition. 1996;64:125-30.
Reference ID: 5109
27. Stenver DI, Gotfredsen A, Hilsted J, Nielsen B. Body composition in hemodialysis
patients measured by dual-energy X-ray absorptiometry. American Journal of
Nephrology. 1995;15:105-10.
Reference ID: 5164
28. Woodrow G, Oldroyd B, Smith MA, Turney JH. Measurement of body composition in
chronic renal failure: comparison of skinfold anthropometry and bioelectrical impedance
with dual energy X-ray absorptiometry. European Journal of Clinical Nutrition.
1996;50:295-301.
Reference ID: 1566
29. Young GA, Kopple JD, Lindholm B, et al. Nutritional assessment of continuous
ambulatory peritoneal dialysis patients: an international study. American Journal of
Kidney Diseases. 1991;17:462-71.
Reference ID: 6439
70
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
Question 3 - adults
1. Brady JP, Hasbargen JA. Correction of metabolic acidosis and its effect on albumin in
chronic hemodialysis patients. American Journal of Kidney Diseases. 1998;31:35-40.
Reference ID: 6
2. Dumler F, Galan M. Impact of acidosis on nutritional status in chronic peritoneal dialysis
patients. Advances in Peritoneal Dialysis. 1996;12:307-10.
Reference ID: 1369
3. Graham KA, Reaich D, Channon SM, Downie S, Goodship THJ. Correction of acidosis in
hemodialysis decreases whole-body protein degradation. Journal of the American Society
of Nephrology. 1997;8:632-7.
Reference ID: 5061
4. Harris DC, Yuill E, Chesher DW. Correcting acidosis in hemodialysis: effect on phosphate
clearance and calcification risk. Journal of the American Society of Nephrology.
1995;6:1607-12.
Reference ID: 2358
5. Kang SW, Lee SW, Lee IH, et al. Impact of metabolic acidosis on serum albumin and other
nutritional parameters in long-term CAPD patients. Advances in Peritoneal Dialysis.
1997;13:249-52.
Reference ID: 395
6. Movilli E, Bossini N, Viola BF, et al. Evidence for an independent role of metabolic acidosis
on nutritional status in haemodialysis patients. Nephrology Dialysis Transplantation.
1998;13:674-8.
Reference ID: 5046
7. Otte KE, Lillevang ST, Rasmussen AG, Christensen HK, Pedersen FB. Acetate or
bicarbonate for haemodialysis: a randomised, double-blind controlled trial. Nephrology,
Dialysis, Transplantation. 1990;5:931-6.
Reference ID: 7553
8. Stein A, Moorhouse J, Iles-Smith H, et al. Role of an improvement in acid-base status and
nutrition in CAPD patients. Kidney International. 1997;52:1089-95.
Reference ID: 101
9. Williams AJ, Dittmer ID, McArley A, Clarke J. High bicarbonate dialysate in
haemodialysis patients: effects on acidosis and nutritional status. Nephrology, Dialysis,
Transplantation. 1997;12:2633-7.
Reference ID: 327
Question 4 - adults
71
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
1. Acchiardo SR, Moore LW, Burk L. Morbidity and mortality in hemodialysis patients.
ASAIO Transactions. 1990;36:M148-M151
Reference ID: 7291
2. Bajardi P, Cravero R, Valenti M, et al. [Protein metabolism and nutritional status in
hemodialysis]. Minerva Urologica e Nefrologica. 1991;43:153-8.
Reference ID: 5993
3. Bergstrom J, Furst P, Alvestrand A, Lindholm B. Protein and energy intake, nitrogen
balance and nitrogen losses in patients treated with continuous ambulatory peritoneal
dialysis. Kidney International. 1993;44:1048-57.
Reference ID: 4072
4. Blumenkrantz MJ, Kopple JD, Moran JK, Grodstein GP, Coburn JW. Nitrogen and urea
metabolism during continuous ambulatory peritoneal dialysis. Kidney International.
1981;20:78-82.
Reference ID: 13048
5. Blumenkrantz MJ, Kopple JD, Moran JK, Coburn JW. Metabolic balance studies and
dietary protein requirements in patients undergoing continuous ambulatory peritoneal
dialysis. Kidney International. 1982;21:849-61.
Reference ID: 12547
6. Davies SJ, Russell L, Bryan J, Phillips L, Russell GI. Comorbidity, urea kinetics, and
appetite in continuous ambulatory peritoneal dialysis patients: their interrelationship and
prediction of survival. American Journal of Kidney Diseases. 1995;26:353-61.
Reference ID: 2389
7. Davies SJ, Russell L, Bryan J, Phillips L, Russell GI. Impact of peritoneal absorption of
glucose on appetite, protein catabolism and survival in CAPD patients. Clinical
Nephrology. 1996;45:194-8.
Reference ID: 1610
8. Fenton SS, Johnston N, Delmore T, et al. Nutritional assessment of continuous ambulatory
peritoneal dialysis patients. ASAIO Transactions. 1987;33:650-3.
Reference ID: 9955
9. Giordano C, De SG, Pluvio M, et al. Protein requirement of patients on CAPD: a study on
nitrogen balance. International Journal of Artificial Organs. 1980;3:11-4.
Reference ID: 13558
10. Guarnieri G, Faccini L, Lipartiti T, et al. Simple methods for nutritional assessment in
hemodialyzed patients. American Journal of Clinical Nutrition. 1980;33:1598-607.
Reference ID: 13518
72
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
11. Ikizler TA, Greene JH, Yenicesu M, Schulman G, Wingard RL, Hakim RM. Nitrogen
balance in hospitalized chronic hemodialysis patients. Kidney International - Supplement.
1996;57:S53-S56
Reference ID: 1281
12. Kopple JD, Shinaberger JH, Coburn JW, Sorensen MK, Rubini ME. Evaluating modified
protein diets for uremia. Journal of the American Dietetic Association. 1969A;54:481-5.
Reference ID: 18223
13. Kopple JD, Shinaberger JH, Coburn JW, Sorensen MK, Rubini ME. Optimal dietary
protein treatment during chronic hemodialysis. Transactions - American Society for
Artificial Internal Organs. 1969B;15:302-8.
Reference ID: 18335
14. Lindner A, Tenckhoff H. Nitrogen balance in patients on maintenance peritoneal dialysis.
Transactions - American Society for Artificial Internal Organs. 1970;16:255-9.
Reference ID: 18071
15. Schilling H, Wu G, Pettit J. Nutritional status of patients on long-term CAPD. Peritoneal
Dial.Bull. 1985;5:12-8.
Reference ID: 4949
16. Slomowitz LA, Monteon FJ, Grosvenor M, Laidlaw SA, Kopple JD. Effect of energy
intake on nutritional status in maintenance hemodialysis patients. Kidney International.
1989;35:704-11.
Reference ID: 8089
17. Wardle EN, Kerr DN, Ellis HA. Serum proteins as indicators of poor dietary intake in
patients with chronic renal failure. Clinical Nephrology. 1975;3:114-8.
Reference ID: 16003
18. Young GA, Young JB, Young SM, et al. Nutrition and delayed hypersensitivity during
continuous ambulatory peritoneal dialysis in relation to peritonitis. Nephron. 1986;43:17786.
Reference ID: 10663
Question 5 - adults
1. Bernard S, Fouque D, Laville M, Zech P. Effects of low-protein diet supplemented with
ketoacids on plasma lipids in adult chronic renal failure. Mineral & Electrolyte
Metabolism. 1996;22:143-6.
Reference ID: 1880
73
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
2. Fouque D, Laville M, Boissel JP, Chifflet R, Labeeuw M, Zech PY. Controlled low protein
diets in chronic renal insufficiency: meta-analysis [see comments]. BMJ. 1992;304:216-20.
Reference ID: 5287
3. Ikizler TA, Greene JH, Wingard RL, Parker RA, Hakim RM. Spontaneous dietary protein
intake during progression of chronic renal failure. Journal of the American Society of
Nephrology. 1995;6:1386-91.
Reference ID: 2250
4. Kopple JD, Monteon FJ, Shaib JK. Effect of energy intake on nitrogen metabolism in
nondialyzed patients with chronic renal failure. Kidney International. 1986;29:734-42.
Reference ID: 10167
5. Kopple JD, Berg R, Houser H, Steinman TI, Teschan P. Nutritional status of patients with
different levels of chronic renal insufficiency. Modification of Diet in Renal Disease
(MDRD) Study Group. Kidney International - Supplement. 1989;27:S184-S194
Reference ID: 7977
6. Maroni BJ, Tom K, Masud T, Chapman T, Young VR. How is lean body mass conserved
with the very-low protein diet regimen?. Mineral & Electrolyte Metabolism. 1996;22:54-7.
Reference ID: 1883
7. Masud T, Young VR, Chapman T, Maroni BJ. Adaptive responses to very low protein
diets: the first comparison of ketoacids to essential amino acids. Kidney International.
1994;45:1182-92.
Reference ID: 4229
8. Park JS, Jung HH, Yang WS, et al. Protein intake and the nutritional status in patients with
pre-dialysis chronic renal failure on unrestricted diet. Korean Journal of Internal Medicine.
1997;12:115-21.
Reference ID: 215
9. Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary protein
restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis
[see comments]. Ann.Intern.Med. 1996;124:627-32.
Reference ID: 5288
10. Pollock CA, Ibels LS, Zhu FY, et al. Protein intake in renal disease. Journal of the
American Society of Nephrology. 1997;8:777-83.
Reference ID: 564
11. Tom K, Young VR, Chapman T, Masud T, Akpele L, Maroni BJ. Long-term adaptive
responses to dietary protein restriction in chronic renal failure. American Journal of
Physiology. 1995;268:E668-E677
Reference ID: 3097
74
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
12. Walser M. Does prolonged protein restriction preceding dialysis lead to protein
malnutrition at the onset of dialysis?. Kidney International. 1993;44:1139-44.
Reference ID: 3940
Question 6 - adults
1. Harty J, Conway L, Keegan M, et al. Energy metabolism during CAPD: a controlled study.
Advances in Peritoneal Dialysis. 1995;11:229-33.
Reference ID: 2414
2. Ikizler TA, Wingard RL, Sun M, Harvell J, Parker RA, Hakim RM. Increased energy
expenditure in hemodialysis patients. Journal of the American Society of Nephrology.
1996;7:2646-53.
Reference ID: 1271
3. Monteon FJ, Laidlaw SA, Shaib JK, Kopple JD. Energy expenditure in patients with
chronic renal failure. Kidney International. 1986;30:741-7.
Reference ID: 10433
4. Olevitch LR, Bowers BM, DeOreo PB. Measurement of resting energy expenditure via
indirect calorimetry among adult hemodialysis patients. Journal of Renal Nutrition.
1994;4:192
Reference ID: 2
5. Schneeweiss B, Graninger W, Stockenhuber F, et al. Energy metabolism in acute and chronic
renal failure [see comments]. American Journal of Clinical Nutrition. 1990;52:596-601.
Reference ID: 7625
Question 7 - adults
1. Allman MA, Stewart PM, Tiller DJ, Horvath JS, Duggin GG, Truswell AS. Energy
supplementation and the nutritional status of hemodialysis patients. American Journal of
Clinical Nutrition. 1990;51:558-62.
Reference ID: 7825
2. Bannister DK, Acchiardo SR, Moore LW, Kraus AJ. Nutritional effects of peritonitis in
continuous ambulatory peritoneal dialysis (CAPD) patients. Journal of the American
Dietetic Association. 1987;87:53-6.
Reference ID: 9993
3. Beutler KT, Park GK, Wilkowski MJ. Effect of oral supplementation on nutrition
indicators in hemodialysis patients. Journal of Renal Nutrition. 1997;7:77
Reference ID: 12
75
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
4. Cano N, Labastie-Coeyrehourq J, Lacombe P, et al. Perdialytic parenteral nutrition with
lipids and amino acids in malnourished hemodialysis patients. American Journal of Clinical
Nutrition. 1990;52:726-30.
Reference ID: 7159
5. Capelli JP, Kushner H, Camiscioli TC, Chen SM, Torres MA. Effect of intradialytic
parenteral nutrition on mortality rates in end-stage renal disease care [see comments].
American Journal of Kidney Diseases. 1994;23:808-16.
Reference ID: 3712
6. Chertow GM, Ling J, Lew NL, Lazarus JM, Lowrie EG. The association of intradialytic
parenteral nutrition administration with survival in hemodialysis patients. American
Journal of Kidney Diseases. 1994;24:912-20.
Reference ID: 3345
7. Hecking E, Kohler H, Zobel R, et al. Is parenteral or oral administration of essential amino
acids beneficial in patients on chronic haemodialysis?. Proceedings of the European
Dialysis & Transplant Association. 1977;14:577-80.
Reference ID: 15171
8. Hecking E, Kohler H, Zobel R, et al. Treatment with essential amino acids in patients on
chronic hemodialysis: a double blind cross-over study. American Journal of Clinical
Nutrition. 1978;31:1821-6.
Reference ID: 14429
9. Kluthe R, Luttgen FM, Capetianu T, Heinze V, Katz N, Sudhoff A. Protein requirements
in maintenance hemodialysis. American Journal of Clinical Nutrition. 1978;31:1812-20.
Reference ID: 14431
10. Maurer O, Saxenhofer H, Jaeger P, Casez JP, Descoeudres C, Horber FF. Six-month
overnight administration of intraperitoneal amino acids does not improve lean mass.
Clinical Nephrology. 1996;45:303-9.
Reference ID: 1560
11. Misra M, Ashworth J, Reaveley DA, Muller B, Brown EA. Nutritional effects of amino
acid dialysate (Nutrineal) in CAPD patients. Advances in Peritoneal Dialysis.
1996;12:311-4.
Reference ID: 1368
12. Neuhauser M, Ulm A, Leber HW, Schutterle G. Influence of essential amino acids and keto
acids on protein metabolism and the anaemia of patients on chronic intermittent
haemodialysis. Proceedings of the European Dialysis & Transplant Association.
1977;14:557-62.
Reference ID: 15176
76
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
13. Rubin J. Nutritional support during peritoneal dialysis-related peritonitis. American
Journal of Kidney Diseases. 1990;15:551-5.
Reference ID: 6964
14. Stewart J, Schvaneveldt NB, Christensen NK, Lauritzen GC, Stein DM. The effect of
computerized dietary analysis nutrition education on nutrition knowledge, nutrition status,
dietary compliance, and quality of life of hemodialysis patients. Journal of Renal Nutrition.
1993;3:177
Reference ID: 10
15. Tietze IN, Pedersen EB. Effect of fish protein supplementation on aminoacid profile and
nutritional status in haemodialysis patients. Nephrology, Dialysis, Transplantation.
1991;6:948-54.
Reference ID: 6546
16. Toigo G, Situlin R, Tamaro G, et al. Effect of intravenous supplementation of a new
essential amino acid formulation in hemodialysis patients. Kidney International Supplement. 1989;27:S278-S281
Reference ID: 7976
17. Ulm A, Neuhauser M, Leber HW. Influence of essential amino acids and keto acids on
protein metabolism and anemia of patients on intermittent hemodialysis. American Journal
of Clinical Nutrition. 1978;31:1827-30.
Reference ID: 14418
18. Wiser NA, Shane JM, McGuigan AT, Memken JA, Olsson PJ. The effects of a group
nutrition education program on nutrition knowledge, nutrition status, and quality of life in
hemodialysis patients. Journal of Renal Nutrition. 1997;7:187-93.
Reference ID: 1
Question 8 - adults
1. Blackburn SL. Dietary compliance of chronic hemodialysis patients. Journal of the
American Dietetic Association. 1977;70:31-7.
Reference ID: 15003
2. De Lima J, Sesso R, Abensur H, et al. Predictors of mortality in long-term haemodialysis
patients with a low prevalence of comorbid conditions. Nephrology, Dialysis,
Transplantation. 1995;10:1708-13.
Reference ID: 2455
77
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
3. Ifudu O, Dulin AL, Friedman EA. Interdialytic weight gain correlates with glycosylated
hemoglobin in diabetic hemodialysis patients. American Journal of Kidney Diseases.
1994;23:686-91.
Reference ID: 3643
4. Manley M, Sweeney J. Assessment of compliance in hemodialysis adaptation. Journal of
Psychosomatic Research. 1986;30:153-61.
Reference ID: 10639
5. Procci WR. Dietary abuse in maintenance hemodialysis patients. Psychosomatics.
1978;19:16-24.
Reference ID: 14799
6. Ruggiero L, Brantley PJ, Bruce BK, McKnight GT, Cocke TB. The role of dietary
compliance in survival of hemodialysis patients. Dialysis Transplant. 1992;21:14-7.
Reference ID: 4885
7. Safdar N, Baakza H, Kumar H, Naqvi SA. Non-compliance to diet and fluid restrictions in
haemodialysis patients. JPMA - Journal of the Pakistan Medical Association.
1995;45:293-5.
Reference ID: 2254
8. Schmicker R, Baumbach A. Dietary compliance in hemodialysis patients. Contributions to
Nephrology. 1990;81:115-23.
Reference ID: 7471
9. Sensky T, Leger C, Gilmour S. Psychosocial and cognitive factors associated with
adherence to dietary and fluid restriction regimens by people on chronic haemodialysis.
Psychotherapy & Psychosomatics. 1996;65:36-42.
Reference ID: 1996
10. Sherman RA, Cody RP, Rogers ME, Solanchick JC. Interdialytic weight gain and nutritional
parameters in chronic hemodialysis patients. American Journal of Kidney Diseases.
1995;25:579-83.
Reference ID: 2406
11. Teraoka S, Toma H, Nihei H, et al. Current status of renal replacement therapy in Japan.
American Journal of Kidney Diseases. 95 A.D.;25:151-64.
Reference ID: 18837
12. Yanitski AE. Compliance of the hemodialysis patient. AANNT Journal. 1983;10:11-6.
Reference ID: 12140
Question 9 – adults
78
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
None selected
Question 10 – adults
None selected
Questions 11, 12 – adults
1. Ahmad S, Robertson HT, Golper TA, et al. Multicenter trial of L-carnitine in maintenance
hemodialysis patients. II. Clinical and biochemical effects. Kidney International.
1990;38:912-8.
Reference ID: 51
2. Albertazzi A, Spisni C, Del Rosso G, Palmieri PF, Rossini PM. Electromyographic changes
induced by oral carnitine treatment in dialysis patients. Proceedings of the Clinical Dialysis
& Transplant Forum. 1980;10:1-6.
Reference ID: 154
3. Albertazzi A, Capelli P, Di Paola B, Pola P, Tondi P, Vaccario O. Endocrine-metabolic
effects of l-carnitine in patients on regular dialysis treatment. Proceedings of the European
Dialysis & Transplant Association. 1983;19:302-7.
Reference ID: 130
4. Bellinghieri G, Savica V, Mallamace A, et al. Correlation between increased serum and
tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients.
American Journal of Clinical Nutrition. 1983;38:523-31.
Reference ID: 118
5. Bellinghieri G, Savica V, Barbera CM, et al. L-carnitine and platelet aggregation in uremic
patients subjected to hemodialysis. Nephron. 1990;55:28-32.
Reference ID: 55
6. Caruso U, Cravotto E, Tisone G. Long-term treatment with L-carnitine in uremic patients
undergoing chronic hemodialysis: Effects on the lipid pattern. Current Therapeutic
Research, Clinical & Experimental. 1983;33:1098-104.
Reference ID: 435
7. Caruso U, Leone L, Cravotto E, Nava D. Effects of L-carnitine on anemia in aged
hemodialysis patients treated with recombinant human erythropoietin: a pilot study.
Dialysis & Transplantation. 1998;27:498-506.
Reference ID: 671
79
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
8. Casciani CU, Caruso U, Cravotto E, et al. L-carnitine in haemodialysed patients. Changes in
lipid pattern. Arzneimittel-Forschung. 1982;32:293-7.
Reference ID: 139
9. Casciani CU, Caruso U, Cravotto E. Beneficial effects of L-carnitine in post dialysis
syndrome. Current Therapeutic Research, Clinical & Experimental. 1982;32:116-27.
Reference ID: 439
10. Dionisio P, Bergia R, Caramello E, et al. [Effects of long-term treatment with L-carnitine on
dyslipemia in hemodialysis patients]. [Italian]. Minerva Medica. 1985;76:229-34.
Reference ID: 108
11. Donatelli M, Terrizzi C, Zummo G, Russo V, Bucalo ML, Scarpinato A. Effects of Lcarnitine on chronic anemia and erythrocyte adenosine triphosphate concentration in
hemodialyzed patients. Curr Ther Res. 1987;41:620-4.
Reference ID: 467
12. Fagher B, Cederblad G, Monti M, Olsson L, Rasmussen B, Thysell H. Carnitine and left
ventricular function in haemodialysis patients. Scandinavian Journal of Clinical &
Laboratory Investigation. 1985;45:193-8.
Reference ID: 106
13. Fagher B, Cederblad G, Eriksson M, et al. L-carnitine and haemodialysis: double blind
study on muscle function and metabolism and peripheral nerve function. Scandinavian
Journal of Clinical & Laboratory Investigation. 1985;45:169-78.
Reference ID: 110
14. Fujita Y, Shinzato T, Takai I, Kobayakawa H, Ozawa Y, Maeda K. Efficacy of L-carnitine
administration for long-term dialysis patients with continuous hypotension. [Japanese].
Japanese Journal of Artificial Organs. 1988;17:132-5.
Reference ID: 478
15. Galeone F, Giacomelli A, Rossi A, Giuntoli F, Micheli C, Saba P. L-carnitine activity on
serum lipid patterns in chronic uraemia. A study of patients on dialysis. Clin Trials J.
1987;24:417-24.
Reference ID: 484
16. Golper TA, Wolfson M, Ahmad S, et al. Multicenter trial of L-carnitine in maintenance
hemodialysis patients. I. Carnitine concentrations and lipid effects. Kidney International.
1990;38:904-11.
Reference ID: 50
80
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
17. Guarnieri G, Toigo G, Crapesi L, et al. Metabolic effects of supplementation of L-carnitine
in the dialysate of patients treated with acetate hemodialysis. Kidney International Supplement. 1989;36, Suppl 27:S247-S255
Reference ID: 59
18. Guarnieri G, Fonda M, Situlin R, Vasile A, Toigo G, Cattin L. Effects of L-carnitine
supplementation in the dialysate on serum lipoprotein composition of hemodialysis
patients. Contributions to Nephrology. 1992;98:36-43.
Reference ID: 41
19. Guarnieri GF, Ranieri F, Toigo G, et al. Lipid-lowering effect of carnitine in chronically
uremic patients treated with maintenance hemodialysis. American Journal of Clinical
Nutrition. 1980;33:1489-92.
Reference ID: 152
20. Huissoon AP, Meehan S, Brian KJ. Carnitine replacement and maintenance by addition of
L-carnitine to dialysis fluid. Journal of Nephrology. 1993;6:103-7.
Reference ID: 511
21. Labonia WD, Morelli OJ, Gimenez MI, Freuler PV, Morelli OH. Effects of L-carnitine on
sodium transport in erythrocytes from dialyzed uremic patients. Kidney International.
1987;32:754-9.
Reference ID: 88
22. Labonia WD. L-carnitine effects on anemia in hemodialyzed patients treated with
erythropoietin. American Journal of Kidney Diseases. 1995;26:757-64.
Reference ID: 18
23. Lundholm K, Persson H, Wennberg A. Whole body fat oxidation before and after carnitine
supplementation in uremic patients on chronic haemodialysis. Clinical Physiology.
1988;8:417-26.
Reference ID: 78
24. Maeda K, Shinzato T, Kobayakawa H. Effects of L-carnitine administration on short-chain
fatty acid (acetic acid) and long-chain fatty acid metabolism during hemodialysis. Nephron.
1989;51:355-61.
Reference ID: 69
25. Mayer G, Graf H, Legenstein E, Linhart L, Auer B, Lohninger A. L-carnitine substitution in
patients on chronic hemodialysis. Nephron. 1989;52:295-9.
Reference ID: 70
81
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
26. Mioli V, Tarchini R, Boggi R. Use of D,L- and L-carnitine in uraemic patients on
intermittent haemodialysis. International Journal of Clinical Pharmacology Research.
1982;2:143-8.
Reference ID: 555
27. Nilsson-Ehle P, Cederblad G, Fagher B, Monti M, Thysell H. Plasma lipoproteins, liver
function and glucose metabolism in haemodialysis patients: lack of effect of L-carnitine
supplementation. Scandinavian Journal of Clinical & Laboratory Investigation.
1985;45:179-84.
Reference ID: 109
28. Rogerson ME, Rylance PB, Wilson R, et al. Carnitine and weakness in haemodialysis
patients. Nephrology, Dialysis, Transplantation. 1989;4:366-71.
Reference ID: 68
29. Siami G, Clinton ME, Mrak R, Griffis J, Stone W. Evaluation of the effect of intravenous
L-carnitine therapy on function, structure and fatty acid metabolism of skeletal muscle in
patients receiving chronic hemodialysis. Nephron. 1991;57:306-13.
Reference ID: 47
30. Sohn HJ, Choi GB, Yoon KI. [L-Carnitine in maintenance hemodialysis clinical, lipid and
biochemical effects]. Kor J Nephrol. 1992;11:260-9.
Reference ID: 603
31. Spagnoli LG, Palmieri G, Mauriello A, et al. Morphometric evidence of the trophic effect of
L-carnitine on human skeletal muscle. Nephron. 1990;55:16-23.
Reference ID: 56
32. Srivastava DK, Kumar S, Misra AP. Reversal of haemodialysis induced
hypertriacylglycerolemia by L-carnitine. Indian Journal of Clinical Biochemistry.
1992;7:19-21.
Reference ID: 296
33. Thompson CH, Irish AB, Kemp GJ, Taylor DJ, Radda GK. The effect of propionyl Lcarnitine on skeletal muscle metabolism in renal failure. Clinical Nephrology. 1997;47:3728.
Reference ID: 3
34. Trivelli G, Vitali P, Girmenia S, Castelli F. Treatment of serum lipid abnormalities in
hemodialysed patients with carnitine [Trattamento della dislipidemia dell'emodializzato con
l-carnitina]. Clin.Eur. 1983;22:405-15.
Reference ID: 612
82
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
35. Trovato GM, Ginardi V, Di Marco V, Dell'Aira AE, Corsi M. Long term L-carnitine
treatment of chronic anaemia of patients with end stage renal failure. Curr Ther Res.
1982;31:1042-9.
Reference ID: 614
36. Vacha GM, Giorcelli G, Siliprandi N, Corsi M. Favorable effects of L-carnitine treatment
on hypertriglyceridemia in hemodialysis patients: decisive role of low levels of high-density
lipoprotein-cholesterol. American Journal of Clinical Nutrition. 1983;38:532-40.
Reference ID: 119
37. Vacha GM, Giorcelli G, D'Iddio S, et al. L-carnitine addition to dialysis fluid. A therapeutic
alternative for hemodialysis patients. Nephron. 1989;51:237-42.
Reference ID: 71
38. van Es A, Henny FC, Kooistra MP, Lobatto S, Scholte HR. Amelioration of cardiac
function by L-carnitine administration in patients on haemodialysis. Contributions to
Nephrology. 1992;98:28-35.
Reference ID: 42
39. Wanner C, Forstner-Wanner S, Schaeffer G, Schollmeyer P, Horl WH. Serum free carnitine,
carnitine esters and lipids in patients on peritoneal dialysis and hemodialysis. American
Journal of Nephrology. 1986;6:206-11.
Reference ID: 102
40. Wanner C, Wieland H, Wackerle B, Boeckle H, Schollmeyer P, Horl WH. Ketogenic and
antiketogenic effects of L-carnitine in hemodialysis patients. Kidney International Supplement. 1989;27:S264-S268
Reference ID: 61
41. Wanner C, Wieland H, Nauck M, Schaeffer G, Schollmeyer P, Horl WH. Effective
hypolipidaemic therapy with beclobrate in haemodialysis patients: Interference with Lcarnitine. Nephrol.Dial.Transplant. 1990;5:588-93.
Reference ID: 243
42. Weschler A, Aviram M, Levin M, Better OS, Brook JG. High dose of L-carnitine increases
platelet aggregation and plasma triglyceride levels in uremic patients on hemodialysis.
Nephron. 1984;38:120-4.
Reference ID: 116
43. Yderstraede KB, Pedersen FB, Dragsholt C, Trostmann A, Laier E, Larsen HF. The effect
of L-carnitine on lipid metabolism in patients on chronic haemodialysis. Nephrology,
Dialysis, Transplantation. 1987;1:238-41.
Reference ID: 94
83
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
44. Zilleruelo G, Novak M, Hsia SL, et al. Effect of dialysate composition on the lipid
response to L-carnitine supplementation. Kidney International - Supplement.
1989;27:S259-S263
Reference ID: 62
84
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
References for Pediatric Sections
Question 1 - pediatrics
A-Peds
1. Chan JC. Late complications of long-term hemodialysis in children: clinical aspects and
some measurable variables concerning parathyroid hormone, divalent ions, acid-base
metabolism, anemia, nutrition, growth and survival data. Journal of Urology.
1978;120:578-85.
Reference ID: 14484
IGF-Peds
1. Besbas N, Ozdemir S, Saatci U, et al. Nutritional assessment of children on haemodialysis:
value of IGF-I, TNF-alpha and IL-1beta. Nephrol Dial Transplant. 1998;13:1484-8.
Reference ID: 7719 (also in B section)
2. Hodson EM, Brown AS, Roy LP, Rosenberg AR. Insulin-like growth factor-1, growth
hormone-dependent insulin-like growth factor-binding protein and growth in children with
chronic renal failure. Pediatr Nephrol. 1992;6:433-8.
Reference ID: 23
3. Jasper HG, Ferraris JR. Insulin-like growth factor I (IGF-I) and growth in children
undergoing hemodialysis or after successful renal transplantation. Medicina (B Aires).
1991;51:127-32.
Reference ID: 30
Question 2 - pediatrics
1. Besbas N, Ozdemir S, Saatci U, et al. Nutritional assessment of children on haemodialysis:
value of IGF-I, TNF-alpha and IL-1beta. Nephrol Dial Transplant. 1998;13:1484-8.
Reference ID: 7719 (also in IGF section)
2. Cochat P, Braillon P, Feber J, et al. Body composition in children with renal disease: use of
dual energy X-ray absorptiometry. Pediatric Nephrology. 1996;10:264-8.
Reference ID: 1666
3. Stefanidis C, Siapera D, Papadopoulou A, Michelis K. Body composition of children on
CAPD. Peritoneal Dialysis International. 1996;16 Suppl 1:S561-S566
Reference ID: 1944
* Reference ID numbers correspond with those listed in the evidence tables.
85
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
Question 3 – pediatrics
None selected
Question 4 - pediatrics
1. Fischbach M, Terzic J, Lahlou A, et al. Nutritional effects of KT/V in children on
peritoneal dialysis: are there benefits from larger dialysis doses? Advances in Peritoneal
Dialysis. 1995;11:306-8.
Reference ID: 28
2. Kleinknecht C, Broyer M, Gagnadoux MF, et al. Growth in children treated with long-term
dialysis. A study of 76 patients. Adv Nephrol Necker Hosp. 1980;9:133-63:133-63.
Reference ID: 132
3. Canepa A, Divino FC, Forsberg AM, et al. Children on continuous ambulatorial peritoneal
dialysis: muscle and plasma proteins, amino acids and nutritional status. Clinical
Nephrology. 1996;46:125-31.
Reference ID: 1311
4. Salusky IB, Fine RN, Nelson P. Nutritional status of children undergoing continuous
ambulatory peritoneal dialysis. Am.J.Clin.Nutr. 1983;38:599-611.
Reference ID: 4965
5. Kohaut EC. Growth in children treated with continuous ambulatory peritoneal dialysis.
Int.J.Pediatr.Nephrol. 1983;4:93-8.
Reference ID: 4966
6. Chan JCM. Late complications of long-term hemodialysis in children: Clinical aspects and
some measurable variables concerning parathyroid hormone, divalent ions, acid-base
metabolism, anemia, nutrition, growth and survival data. J.Urol. 1978;120:578-85.
Reference ID: 4997
7. Zadik Z, Frishberg Y, Drukker A, et al. Excessive dietary protein and suboptimal caloric
intake have a negative effect on the growth of children with chronic renal disease before and
during growth hormone therapy. Metabolism: Clinical and Experimental. 1998;47:264-8.
Reference ID: 5041
8. Honda M, Kamiyama Y, Kawamura K, et al. Growth, development and nutritional status in
Japanese children under 2 years on continuous ambulatory peritoneal dialysis. Pediatric
Nephrology. 1995;9:543-8.
Reference ID: 5143
86
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
9. Querfeld U, Salusky IB, Nelson P, Foley J, Fine RN. Hyperlipidemia in pediatric patients
undergoing peritoneal dialysis. Pediatric Nephrology. 1988;2:447-52.
Reference ID: 8807
10. Macdonald A. The practical problems of nutritional support for children on continuous
ambulatory peritoneal dialysis. Human Nutrition - Applied Nutrition. 1986;40:253-61.
Reference ID: 10271
11. Broyer M, Niaudet P, Champion G, Jean G, Chopin N, Czernichow P. Nutritional and
metabolic studies in children on continuous ambulatory peritoneal dialysis. Kidney
International - Supplement. 1983;15:S106-S110
Reference ID: 11953
12. Broyer M, Kleinknecht C, Loirat C, Marti-Henneberg C, Roy MP. Growth in children
treated with long-term hemodialysis. Journal of Pediatrics. 1974;84:642-9.
Reference ID: 16260
Question 5 - pediatrics
1. Claris-Appiani A, Ardissino GL, Dacco V, Funari C, Terzi F. Catch-up growth in children
with chronic renal failure treated with long-term enteral nutrition. Jpen: Journal of
Parenteral & Enteral Nutrition. 1995;19:175-8.
Reference ID: 2282
2. Uauy RD, Hogg RJ, Brewer ED, Reisch JS, Cunningham C, Holliday MA. Dietary protein
and growth in infants with chronic renal insufficiency: a report from the Southwest
Pediatric Nephrology Study Group and the University of California, San Francisco.
Pediatric Nephrology. 1994;8:45-50.
Reference ID: 3871
3. Ratsch IM, Catassi C, Verrina E, et al. Energy and nutrient intake of patients with mild-tomoderate chronic renal failure compared with healthy children: an Italian multicentre study.
European Journal of Pediatrics. 1992;151:701-5.
Reference ID: 5007
4. Zadik Z, Frishberg Y, Drukker A, et al. Excessive dietary protein and suboptimal caloric
intake have a negative effect on the growth of children with chronic renal disease before and
during growth hormone therapy. Metabolism: Clinical and Experimental. 1998;47:264-8.
Reference ID: 5041
87
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
5. Wingen AM, Fabian-Bach C, Mehls O. Multicentre randomized study on the effect of a
low-protein diet on the progression of renal failure in childhood: one-year results. European
Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. Mineral &
Electrolyte Metabolism. 1992;18:303-8.
Reference ID: 5510
6. Abitbol CL, Warady BA, Massie MD, et al. Linear growth and anthropometric and
nutritional measurements in children with mild to moderate renal insufficiency: a report of
the Growth Failure in Children with Renal Diseases Study. Journal of Pediatrics.
1990;116:S46-S54
Reference ID: 7784
7. Rizzoni G, Basso T, Setari M. Growth in children with chronic renal failure on conservative
treatment. Kidney International. 1984;26:52-8.
Reference ID: 11503
8. Betts PR, Magrath G. Growth pattern and dietary intake of children with chronic renal
insufficiency. British Medical Journal. 1974;2:189-93.
Reference ID: 16464
9. Ruley EJ, Bock GH, Kerzner B, Abbott AW, Majd M, Chatoor I. Feeding disorders and
gastroesophageal reflux in infants with chronic renal failure. Pediatr Nephrol. 1989;3:424-9.
Reference ID: 16465
10. Kist-van Holthe tEJ, Nauta J, Hop WC, et al. Protein restriction in chronic renal failure.
Arch.Dis Child. 1993;68:371-5.
Reference ID: 16466
11. Arnold WC, Danford D, Holliday MA. Effects of caloric supplementation on growth in
children with uremia. Kidney Int. 1983;24:205-9.
Reference ID: 16467
12. Betts PR, Magrath G, White RH. Role of dietary energy supplementation in growth of
children with chronic renal insufficiency. Br.Med J. 1977;1:416-8.
Reference ID: 16468
Question 6 – pediatrics
None Selected
Question 7 - pediatrics
88
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
1. Balfe JW, Secker DJ, Coulter PE, Balfe JA, Geary DF. Tube feeding in children on chronic
peritoneal dialysis. Adv Perit.Dial. 1990;6:257-61:257-61.
Reference ID: 17651
2. Brewer ED. Growth of small children managed with chronic peritoneal dialysis and
nasogastric tube feedings: 203-month experience in 14 patients. Advances in Peritoneal
Dialysis. 1990;6:269-72.
Reference ID: 7039
3. Canepa A, Perfumo F, Carrea A, et al. Long-term effect of amino-acid dialysis solution in
children on continuous ambulatory peritoneal dialysis. Pediatric Nephrology. 1991;5:2159.
Reference ID: 6682
4. Coleman JE, Watson AR. Micronutrient supplementation in children on continuous cycling
peritoneal dialysis (CCPD). Advances in Peritoneal Dialysis. 1992;8:396-401.
Reference ID: 5068
5. Coleman JE, Watson AR, Rance CH, Moore E. Gastrostomy buttons for nutritional
support on chronic dialysis. Nephrol Dial Transplant. 1998;13:2041-6.
Reference ID: 17648
6. Dabbagh S, Fassinger N, Clement K, Fleischmann LE. The effect of aggressive nutrition on
infection rates in patients maintained on peritoneal dialysis. Advances in Peritoneal
Dialysis. 1991;7:161-4.
Reference ID: 6044
7. Dello SL, Principato F, Sinibaldi D, et al. Feeding dysfunction in infants with severe chronic
renal failure after long-term nasogastric tube feeding. Pediatr Nephrol. 1997;11:84-6.
Reference ID: 17650
8. Hanning RM, Balfe JW, Zlotkin SH. Effectiveness and nutritional consequences of amino
acid-based vs glucose-based dialysis solutions in infants and children receiving CAPD.
American Journal of Clinical Nutrition. 1987;46:22-30.
Reference ID: 9639
9. Kaiser BA, Polinsky MS, Stover J, Morgenstern BZ, Baluarte HJ. Growth of children
following the initiation of dialysis: a comparison of three dialysis modalities. Pediatric
Nephrology. 1994;8:733-8.
Reference ID: 4
10. Warady BA, Weis L, Johnson L. Nasogastric tube feeding in infants on peritoneal dialysis.
Perit.Dial Int. 1996;16 Suppl 1:S521-5:S521-S525
Reference ID: 17649
89
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
11. Zachwieja J, Duran M, Joles JA, et al. Amino acid and carnitine supplementation in
haemodialysed children. Pediatric Nephrology. 1994;8:739-43.
Reference ID: 3385
Question 8 – pediatrics
None Selected
Question 13 – pediatrics
1. Berard E, Crosnier H, Six-Beneton A, Chevallier T, Cochat P, Broyer M. Recombinant
human growth hormone treatment of children on hemodialysis. French Society of Pediatric
Nephrology. Pediatr Nephrol. 1998;12:304-10.
Reference ID: 18823
2. Fine RN, Koch VH, Boechat MI, et al. Recombinant human growth hormone (rhGH)
treatment of children undergoing peritoneal dialysis. Peritoneal Dialysis International.
1990;10:209-14.
Reference ID: 7590
3. Greco M, Cappa M, Perruzza I, Rizzoni G. Can provocative growth hormone testing
predict the response to recombinant human growth hormone (rhGH) treatment?. British
Journal of Clinical Practice.Supplement. 1996;85:38-40.
Reference ID: 977
4. Hokken-Koelega AC, Stijnen T, de MS, et al. Placebo-controlled, double-blind, cross-over
trial of growth hormone treatment in prepubertal children with chronic renal failure. Lancet.
1991;338:585-90.
Reference ID: 5933
5. Laron Z, Wang XL, Klinger B, et al. Growth hormone treatment increases circulating
lipoprotein(a) in children with chronic renal failure. J Pediatr Endocrinol.Metab.
1996;9:533-7.
Reference ID: 10
6. Lippe B, Yadin O, Fine RN, Moulton L, Nelson PA. Use of recombinant human growth
hormone in children with chronic renal insufficiency: an update. Hormone Research.
1993;40:102-8.
Reference ID: 4470
90
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
7. Schaefer F, Wuhl E, Haffner D, Mehls O. Stimulation of growth by recombinant human
growth hormone in children undergoing peritoneal or hemodialysis treatment. German
Study Group for Growth Hormone Treatment in Chronic Renal Failure. Advances in
Peritoneal Dialysis. 1994;10:321-6.
Reference ID: 3451
8. Schwartz ID, Warady BA, Buchanan CL, et al. "Low-dose" growth hormone therapy
during peritoneal dialysis or following renal transplantation. Pediatric Nephrology.
1995;9:320-4.
Reference ID: 2634
9. Tonshoff B, Mehis O, Heinrich U, Blum WF, Ranke MB, Schauer A. Growth-stimulating
effects of recombinant human growth hormone in children with end-stage renal disease.
Journal of Pediatrics. 1990;116:561-6.
Reference ID: 7841
10. Tonshoff B, Dietz M, Haffner D, Tonshoff C, Stover B, Mehls O. Effects of two years of
growth hormone treatment in short children with renal disease. The German Study Group
for Growth Hormone Treatment in Chronic Renal Failure. Acta Paediatrica Scandinavica Supplement. 1991;379:33-41.
Reference ID: 6449
11. Vaisman N, Zadik Z, Duchan R, Voet H, Lotan D, Drukker A. Changes in body
composition of children with chronic renal failure during growth hormone treatment.
Pediatric Nephrology. 1994;8:201-4.
Reference ID: 3946
12. Wuhl E, Haffner D, Tonshoff B, Mehls O. Predictors of growth response to rhGH in short
children before and after renal transplantation. German Study Group for Growth Hormone
Treatment in Chronic Renal Failure. Kidney International - Supplement. 1993;43:S76-S82
Reference ID: 4182
13. Wuhl E, Haffner D, Nissel R, Schaefer F, Mehls O. Short dialyzed children respond less to
growth hormone than patients prior to dialysis. German Study Group for Growth
Hormone Treatment in Chronic Renal Failure. Pediatric Nephrology. 1996;10:294-8.
Reference ID: 1671
14. Zadik Z, Frishberg Y, Drukker A, et al. Excessive dietary protein and suboptimal caloric
intake have a negative effect on the growth of children with chronic renal disease before and
during growth hormone therapy. Metabolism. 1998;47:264-8.
Reference ID: 18821
Question 14 – pediatrics
91
APPENDIX D: BIBLIOGRAPHY OF ACCEPTED ARTICLES (CONTINUED)
1. Kriley M, Warady BA. Vitamin status of pediatric patients receiving long-term peritoneal
dialysis. Am J Clin Nutr. 1991;53:1476-9.
Reference ID: 47
2. Warady BA, Kriley M, Alon U, Hellerstein S. Vitamin status of infants receiving long-term
peritoneal dialysis. Pediatr Nephrol. 1994;8:354-6.
Reference ID: 27
3. Zlotkin SH, Rundle MA, Hanning RM, Buchanan BE, Balfe JW. Zinc absorption from
glucose and amino acid dialysis solutions in children on continuous ambulatory peritoneal
dialysis (CAPD). J Am Coll.Nutr. 1987;6:345-50.
Reference ID: 176
92
A PPENDIX E: ABSTRACTION F O R M S
NKF Prognostic Article Abstract Form
Date: ___________________
Reference ID Number: _________
First author’s last name: ________________________
Reviewer: MH SK SW ES TT GD
Publication year: 19_____
Type of study: Case control / Prospective cohort / Retrospective cohort / Unsure
-If not a prospective cohort and not a carnitine or pediatric acticle, StopStudy population and dialysis characteristics:
Number of patients at start of study: ___________________
Years on dialysis: ________________
Age of patients: __________________
Type of dialysis:
HD __________,
CAPD ______________
Dialysate: _____________________
Membrane: ____________________,
Reused? Y/N
Dialysis schedule: __________ exchanges/day for CAPD,
sessions/wk @ _________ hrs/session for HD
_____________
For HD, vascular access: ____Temporary, _____Permanent
Economic status: ________________________________________________
Race: _________________________________________________________
Residual renal function: ___________________________________________
93
APPENDIX E: ABSTRACTION FORMS (CONTINUED)
Top 3 co-morbid conditions: ________________________________________
_______________________________________________________________
Representative and well-defined sample of patients at a similar point in the course of
disease? Y / N
Follow-up time period: ____________________________________________
Outcome criteria objective and application of them unbiased?
Y/N
Adjustment for important known prognostic factors (see above)?
Y/N
Reported results (point estimate and confidence interval or p-value):
Outcome:
#1
#2
#3
________
_________ ________
Prog factor 1: _____________________ ________
_________ ________
CI or p-value
________
_________ ________
Prog factor 2: _____________________ ________
_________ ________
CI or p-value
________
_________ ________
Prog factor 3: _____________________ ________
_________ ________
CI or p-value
________
_________ ________
Prog factor 4: _____________________ ________
_________ ________
CI or p-value
_________ ________
________
Comments:
_______________________________________________________________
_______________________________________________________________
94
APPENDIX E: ABSTRACTION FORMS (CONTINUED)
NKF Diagnostic Article Abstract Form
Date:__________________
Reference ID Number: _________
First author’s last name: ________________________
Reviewer: MH SK SW ES TT GD MP
Publication year: 19_____
Type of study: Prospective / Retrospective / Unsure
Study population and dialysis characteristics:
Number of patients at start of study: ___________________
Years on dialysis: ________________
Age of patients: __________________
Type of dialysis:
HD __________,
CAPD ______________
Dialysate: _____________________
Membrane: ____________________,
Reused? Y/N
Dialysis schedule: __________ exchanges/day for CAPD,
sessions/wk @ _________ hrs/session for HD
_____________
Dose of dialysis (Kt/V): ____________________________________
For HD, vascular access: ____Temporary, _____Permanent
Economic status: ________________________________________________
Race: _________________________________________________________
Residual renal function: ___________________________________________
95
APPENDIX E: ABSTRACTION FORMS (CONTINUED)
Top 3 co-morbid conditions: ________________________________________
Independent blind comparison with a reference (gold) standard?
Y/N
(If Yes, list reference standard: _______________________________________)
--If No and not carnitine or pediatric article, Stop--
Did results of test influence decision to perform the reference standard? Y / N
Spectrum of patients in study similar to spectrum seen in dialysis centers? Y / N
Test methodology described well enough to be reproducible?
Y/N
Results (test characteristics):
Test
Sens
Spec
LR+
LR-
No 1:___________________________
____
____
____
____
No 2:___________________________
____
____
____
____
No 3:___________________________
____
____
____
____
No 4:___________________________
____
____
____
____
No 5:___________________________
____
____
____
____
No 6:___________________________
____
____
____
____
Comments:
_______________________________________________________________
_______________________________________________________________
96
APPENDIX E: ABSTRACTION FORMS (CONTINUED)
NKF Treatment Article Abstract Form
Date: _______________________
Reference ID Number: _________
First author’s last name: ________________________
Reviewer: MH SK SW ES
Publication year: 19_____
Type of study: Case control / RCT / Non-randomized clinical trial / Cross-over /
Unsure
-If not a clinical trial and not a carnitine or pediatric article, StopStudy population and dialysis characteristics:
Number of patients at start of study: ___________________
Years on dialysis: ________________
Age of patients: __________________
Type of dialysis:
HD __________,
CAPD ______________
Dialysate: _____________________
Membrane: ____________________,
Reused? Y/N
Dialysis schedule: __________ exchanges/day for CAPD,
sessions/wk @ _________ hrs/session for HD
_____________
For HD, vascular access: ____Temporary, _____Permanent
Economic status: ________________________________________________
Race: _________________________________________________________
Residual renal function: ___________________________________________
97
APPENDIX E: ABSTRACTION FORMS (CONTINUED)
Top 3 co-morbid conditions: ________________________________________
Jadad and Schulz score (see scoring guidelines):
•
Randomization score (0,1 or 2)
_______
•
Double blind score (0,1 or 2)
_______
•
All patients accounted for score (0 or 1) _______
Analyzed in treatment group to which assigned?
Treatment groups similar at baseline?
Y/N
Y/N
Treatment groups treated equally except for studied intervention?
Y/N
Treatments and sample size (Intention to treat and Per Protocol):
Treatment/Control
ITT
PP
Rx1=___________________________
_____
_____
Rx2=___________________________
_____
_____
Rx3=___________________________
_____
_____
Rx4=___________________________
_____
_____
Reported results (point estimate and confidence interval):
Outcome/result:
Rx1
Rx2
Rx3
Rx4
No. 1-ITT________________________
_____
_____
_____
_____
No. 1-PP________________________
_____
_____
_____
_____
No. 2-ITT________________________
_____
_____
_____
_____
No. 2-PP________________________
_____
_____
_____
_____
No. 3-ITT________________________
_____
_____
_____
_____
No. 3-PP________________________
_____
_____
_____
_____
98
APPENDIX E: ABSTRACTION FORMS (CONTINUED)
No. 4-ITT________________________
_____
_____
_____
_____
No. 4-PP________________________
_____
_____
_____
_____
No. 5-ITT________________________
_____
_____
_____
_____
No. 5-PP________________________
_____
_____
_____
_____
No. 6-ITT________________________
_____
_____
_____
_____
No. 6-PP________________________
_____
_____
_____
_____
No 1: ___________________
_____
_____
_____
_____
No 2: ___________________
_____
_____
_____
_____
No 3: ___________________
_____
_____
_____
_____
No 4: ___________________
_____
_____
_____
_____
Adverse effects:
Comments:
_______________________________________________________________
_______________________________________________________________
99
A PPENDIX F: TREATMENT A RTICLE Q UALITY S CORE A L G O R I T H M
1. Was the study described as randomized?
2. Was the study described as double-blind?
3. Was there a description of withdrawals and drop-outs?
Give a score of 1 point for each ‘Yes’ or 0 points for each ‘No’
Give 1 additional point each
Deduct 1 point each
If randomization/blinding appropriate
If randomization/ blinding inappropriate
Scoring Range: 0-5
Poor Quality < 3
Jadad et al. Controlled Clinical Trials 1996;17:1-12
100
APPENDIX F: TREATMENT ARTICLE QUALITY SCORE ALGORITHM (CONTINUED)
GUIDELINES FOR ASSESSMENT: JADAD QUALITY SCALE
1. Randomization
A method to generate the sequence of randomization will be regarded as appropriate if it allowed each study
participant to have the same chance of receiving each intervention and the investigators could not predict which
treatment was next. Methods of allocation using date of birth, date of admission, hospital numbers, or alternation
should not be regarded as appropriate.
2. Double blinding
A study must be regarded as double blind if the word “double blind” is used. The method will be regarded as
appropriate if it is stated that neither the person doing the assessment nor the study participant could identify the
intervention being assessed, or if in the absence of such a statement for use of active placebos, identical placebos,
or dummies is mentioned.
3. Withdrawals and Dropouts
Participants who were included in the study but did not complete the observation period or who were not included
in the analysis must be described. The number and the reasons for withdrawals in each group must be stated. If
there were no withdrawals, it should be stated in the article. If there is no statements or withdrawals, this item
must be given no points.
101
A PPENDIX G: EVIDENCE T A B L E S
abbreviation
#
↑
↓
∆
µmol/l
AA
AC
ADV
AMC
asymp.
BA
BIA-PA
bicarb.
BMI
BSA
BUN
Bwt
CAPD
cf
Cr
CRF
CPD
d
DEI
DEXA
DF
dial.
DPI
EAA
ESRD
f/b
FFM 4CM
GH
GT
Gluc
gm
meaning
number / count
increased
decreased
change
micro moles per liter
Amino Acid (also see EAA, NEAA)
Arm Circumference
Antipyrine Distribution Volume
Arm Muscle Circumference
asymptomatic
"Before and After" study (no concurrent
controls)
Bioimpedance Analysis-Phase Angle
bicarbonate
Body Mass Index
Body Surface Area
Blood Urea Nitrogen
Body Weight
Continuous Ambulatory Peritoneal Dialysis
compared with
Creatinine
Chronic Renal Failure
Chronic Peritoneal Dialysis
days
Dietary Energy Intake
dual energy X-ray absorptiometry
Discriminant Function
dialysis
Dietary Protein Intake
Essential Amino Acid (also see AA, NEAA)
End Stage Renal Disease
followed by
Fat Free Mass - Four Compartment Model
Growth Hormone
Gastrostomy Tube
Glucose
gram
102
A PPENDIX G: EVIDENCE TABLES (CONTINUED )
abbreviation
HD
HgB
hr
HPNI
HV
IBW
IDPN
IDWN
IPD
ITT
IU
IV
IVNAA
K (or K+)
kg
MAC
MAMC
min
ml
mo
N
N/A
NEAA
NGT
nPCR
nl
NR
NRCT
NS
NSD
OR
O/E
pt(s)
P
PCR
PCRn
PD
PDPN
Phos
meaning
Hemodialysis
Hemoglobin
hour(s)
Hemodialysis Prognostic Nutrition Index
Height Velocity
Ideal Body Weight
Intradialytic Parenteral Nutrition
Intradialytic Weight Gain
Intermittent Peritoneal Dialysis
Intention to treat analysis
International Units
intravenous
in vivo neutron activation analysis
Potassium
kilogram
Mid-arm circumference
Mid-arm muscle circumference
minutes
milliliters
month(s)
sample size (or "No" depending on context)
not applicable
Non-essential Amino Acid (also see AA,
EAA)
Nasogastric Tube
normalized Protein Catabolic Rate (see also
PCR)
normal
Not Reported
Non Randomized Clinical Trial
not statistically significant
no significant difference/change
Odds Ratio
Observed/Exepected
patient(s)
P-value (statistical significance)
Protein Catabolic Rate (see also nPCR)
see nPCR
Peritoneal Dialysis
Per Dialytic Parenteral Nutrition
Phosphorus
103
A PPENDIX G: EVIDENCE TABLES (CONTINUED )
abbreviation
PO
PP
qd
q wk
r
RCT
RDA
RR
Rx
SDS
SFT
SGA
SSF
Stand Dev
symp.
sx
TBK
TBPr
Technique
Failure
TSF
TSFT
TST
URR
vs
w/
w/o
wks
Wt
WI
Y
Z Score
meaning
by mouth
Per-protocol analysis
per day
per week
Regression Coefficient
Randomized Controlled Clinical Trial
Recommended Daily Allowance
Relative Risk
Treatment / Intervention
Standard Deviation Score
Skin Fold Thickness
Subjective Global Assessment
Subscapular skinfold
Standard Deviation
symptomatic
symptoms
Total Body Potassium
Total Body Protein
CAPD failed; required hemodialysis
Triceps skinfold thickness (also see TST)
see TSF, TST
Triceps skinfold thickness (also see TSF)
Urea Reduction Rate
versus
with
without
week(s)
Weight
Weight Index
Yes
Standard Deviation Score
NB: data in italics not reported in study but inferred by
abstractor
104