Introduction
Dialytic therapy is the method used to maintain life in most uremic patients. According to
the statistical results of the Taiwan Society of Nephrology,1 the dialytic population has
increased 7% per year in Taiwan since 1994, that is, after the national health insurance
scheme was instructed. There have been 41,675 dialytic people in Taiwan until 2005. The
prevalence of dialysis is ranked second in the world, which severely threatens public health
finances. Pruritus is a common distressing symptom affecting many long-term dialytic
patients. The prevalence of uremic pruritus ranges between 40 and 90%.2-4 The symptoms of
dry skin and itch in peritoneal dialytic patients ranges between 50 and 62%. However, the
symptoms in hemodialytic patients ranges between 51 and 86%.5-6 The patients suffering from
generalized itching ranges between 19 and 47%. Otherwise, the patients suffer from localized
itching ranges between 17 and 61%.4, 6-8 The itching is strongest on back, the extremities, the
area where the catheter is implanted, or the face and is associated with dry skin, xerosis and
secondary infection.3, 9
Among the patients with itching of the skin, 36% became irritable, 8% became depressed
and over 40% felt their emotions were affected, even causing sleep disorders.7, 8, 10 All of
these data revealed that patients suffer greatly from uremic pruritus. Many research studies
relate to uremic pruritus, but their results are inconsistent. Since there are no data showing
predictors for uremic pruritus in dialytic patients, the purpose of this study was to identify the
related factors of uremic pruritus in dialytic patients and to construct a predictive model.
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Materials and Methods
Study design
The study was a cross-sectional design and adapted a structured questionnaire. 110
dialysis subjects were recruited from a medical center in Taipei, Taiwan between December
2006 and March 2007 by purposive sampling. Out of which 76 subjects were on peritoneal
dialysis and 34 subjects on hemodialysis three times per week, four hours per time. Data were
collected during the week in which we took blood samples for checking the physiological
parameters of the patients. The inclusive criteria were as follows: 1) to be aged 18 years or
older; 2) to be alert; 3) to be able to write or communicate in Chinese or Taiwanese; 4) to have
been on dialytic therapy for more than six months; 5) not to suffer from mental disorder, other
dermatologic disorder, systemic disease such as severe infection, hepatic failure,
hematological disorder or biliary tract disorder. All patients signed a written consent form
prior to the start of the study.
Measures
A comprehensive questionnaire was used to collect data. It included the basic
characteristics of the patients (demographic, disease, dialytic, and trait anxiety), physiological
parameters, and pruritic score.
In terms of demographic characteristics, age, sex, occupation before dialysis, current
occupation and religion were collected. Disease characteristics included the types of renal
disease and residual renal function. The pre-dialytic creatinine clearance rate (CCr)
formulated by Gault,11 was used to estimate the residual renal function of patients. With
regard to dialytic characteristics, these included the dialytic method, dialytic membrane and
adequacy of dialysis. We took the formula of Kt/Vurea by Gotch and Sargent,12 published to
estimate the adequacy of dialysis. Concerning anxiety, this was described as an unpleasant
emotional state consisting of feelings of uncertainly.13 Spielberger14 indicated that it consisted
of state anxiety and trait anxiety. The trait anxiety is the individualized anxiety level that
changes with the situation. The Chinese language version of trait anxiety translated and
revised by Chung and Long15 was used in this study. It included 7 items of negative questions
and 13 items of positive questions. Each item was rated on a 4-point Likert scale, where a
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higher score indicated a higher anxious personality. Cronbach’s alpha in the present study was
0.88.
Hematology laboratory data and skin measurements were included in physiologic
parameters. The laboratory data of creatinine, total calcium, free calcium, phosphate, calcium
and phosphorus products (Ca*P), hematocrit, parathyroid hormone (PTH), blood urea
nitrogen (BUN), chloride, triglyceride and magnesium were obtained from the medical record.
In respect of skin measurement, we adapted the multi probe adaptor (MPA) made by
Courage-Khazaka Electronic GmbH in Germany, to measure skin humidity and
transepidermal water loss (TEWL). The MPA was corrected and checked regularly by
professional engineers to ensure its precision.
Pruritus is a subjective experience of uncomfortable and unpleasant sensation, which
elicits the desire to scratch.16 The definition of uremic pruritus by Duo17 is of itching bouts
lasting more than 10 minutes, or if not, the total number of itching bouts had to be more than
20 times per half a day. For this study we translated and modified both Duo’s17 and
Hung’s18 scales to evaluate severity, frequency, distribution and sleep disturbance during
day or night by patients’ recall. In terms of pruritus severity, this was rated on a 4-point
Likert scale (0＝no pruritus, 1＝itching without annoyance or necessity for scratching, 2＝a
few times of scratching, 3＝frequent scratching, 4＝scratching without relief of itching, or
total restlessness). A maximum of 8 points can thus be given during the day (4 in the morning,
4 in the afternoon). For distribution, a maximum of 6 points can be given over the day, 3 in
the morning and 3 in the afternoon. Without pruritus = 0 point; itching in one single location =
1 point; scattered itching = 2 points; generalized itching = 3 points. Frequency of pruritus was
judged by the number of itching bouts and the duration of episodes. Every four short itching
bouts (< 10 min) or one long bout (≧ 10 min) received 1 point and no pruritus received 0
point. Thus a maximum of 5 points can be given during the day. Sleep disturbance was judged
by waking-up periods during the night for scratching. Waking up once because of itching
scored 2 points. Thus a maximum of 14 points can be given during the night. The highest
possible score was 38 points. In our study, we invited five nephrology, dermatology and
nursing experts to check validity. The content validity index (CVI) of the scale was 1. The
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Cronbach’s alpha was 0.9 at the formal study.
Statistical analysis
For analysis of the variables the following tests were used: mean, standard deviation,
frequency, percentage, chi-square test, student’s t test and multiple logistic regression model.
The analysis was performed using SPSS 13.0 for Windows. P ＜ .05 was considered
statistically significant.
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Results
Distribution of basic characteristics
The average age of 110 patients was 53.21±14.59 years (mean±SD), 53.06 years in the
itch group and 53.56 years in the non-itch group respectively. The average pre-dialytic CCr
was 5.74±1.62ml/min, 5.49 ml/min in the itch group and 6.34 ml/min in the non-itch group
respectively. The average Kt/Vurea was 1.87±0.53, 1.86 in the itch group and 1.91 in the
non-itch group respectively. The average trait anxiety inventory was 43.08±9.92, 43.07 in the
itch group and 40.81 in the non-itch group respectively. Other characteristics are shown in
Table 1.
Distribution of physiological parameters
The physiological parameters of creatinine, Ca*P, PTH, BUN, chloride, skin humidity,
phosphate, and total calcium among the itch group were statistically significant compared
with the non-itch group. Other parameters are shown in Table 2.
Distribution of pruritus in uremic dialytic patients
We used the definition by Zucker et al.8of an itching person, i.e. the appearance of an itch
in a regular pattern during a period of six months. Of the 110 patients, 78 (70.9%) had pruritus.
Of the 76 peritoneal dialytic patients, 55 (72.4%) had pruritus and of the 34 hemodialytic
patients, 23 (67.6%) had prurirtus. The pruritic scale ranged from 0 to 34 (mean±SD: 7.75±
7.17). For severity, the score in the afternoon (1.65) was higher than morning (1.45) and for
frequency, the score in the afternoon (0.97) was significantly higher than morning (0.64)
(t=-3.04，p<0.05). In addition, the average waking-up for scratching during the night was
once.
The predictors for uremic pruritus
Univariate logistic regression analysis was performed to define the every variables used
for itching and non-itching. The significant univariables included occupation before dialysis,
religion, diabetic nephropathy, lupus nephritis, other renal disease, pre-dialytic CCr, creatinine,
Ca*P, PTH, BUN, chloride and skin humidity. Then the multivariate analysis of logistic
regression was performed. The predictors included occupation before dialysis (Odds=4.11,
95%C. I.: 1.06-15.94), lupus nephritis (Odds=0.08, 95%C. I.: 0.01-0.95), other renal disease
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(Odds=0.07, 95%C. I.: 0.01-0.70), chloride (Odds=0.87, 95%C. I.: 0.75-0.99) and skin
humidity (Odds=0.94, 95%C. I.: 0.88-0.99). They accounted for 40% of the variance in
uremic dialytic patients with pruritus (Table 3).
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Discussion
After controlling the other variables, the multiple logistic regression revealed the
significant factors to be occupation before dialysis, the types of renal disease, chloride, and
skin humidity. Patients who worked before dialysis and with unknown renal disease, low
chloride and low skin humidity easily incurred uremic pruritus. In terms of literature, from the
Medline database 1987-2006, there were only two studies, Mistik et al.19 and Narita et al.,20
who used multiple logistic regression for data analysis. Most studies used univariate logistic
regression. As a result, our discussion is divided into two parts with regard to statistics used.
In terms of multiple logistic regression, the types of renal disease, the odds of the
occurrence of pruritus among lupus nephritis compared with the unknown renal disease, was
significantly lower (Odds=0.08; 95%CI=0.01-0.95) and the odds of occurrence of pruritus
among others renal diseases was also significantly lower (Odds=0.07; 95%CI=0.01-0.70).
These findings were different from the results in the Mistik et al.’s study.19 The possible
explanation for these findings might be that we took the unknown renal disease as a reference
group, but Mistik et al.19 did not consider the effect of unknown renal disease. Otherwise,
their study showed that the patients with liver disease were more likely to have pruritus, but
our study had excluded patients with hepatic failure or biliary tract disorder. The reason was
that we considered that patients with liver disease might confound the uremic pruritus.
However, as the study by Narita et al.20 did not discuss the types of renal disease, we could not
compare our results with that study. In addition, when skin humidity decreased by one unit,
the odds of occurrence of pruritus were higher. However, the studies by Mistik et al.19 and
Narita et al.20 did not discuss skin humidity in their regression model. Otherwise the calcium,
phosphate, BUN and PTH were significant predictors in the model used by Narita et al.20 The
results were not consistent with this study. The possible reason might be that the authors
separated the variables into categorical variables and the variables as continuous in this study.
According to univariate analysis, we found the skin humidity in nonpruritic patients was
significantly higher than in pruritic patients (see Table 2). The result demonstrated that the
skin was more humid in nonprurituc patients with similar results in the studies by Robertson
and Mueller3 and Szepietowski et al.4 All findings showed that the uremic patients might have
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stratum corneum, exogenous gland and sebaceous function impairment during the progress of
disease, which in turn decreased the skin humidity and xerosis occurred. Xerosis might affect
the terminal nerve on the skin surface or decreased the threshold of itching to induce uremic
pruritus.3-4 The above results demonstrated that the patients with low skin humidity or
electrolyte imbalance incurred pruritus easily.2, 4 In addition, the pre-dialytic CCr, Ca*P, BUN
and PTH were significant in the univariate logistic regression in this study. When the
pre-dialytic CCr decreased one unit, the odds of occurrence of pruritus was significantly
higher (Odds=0.73; 95%CI=0.56-0.95). The reason might be that the worse residual renal
function will retain metabolic materials in the body to induce pruritus. Similar results were
achieved by Hiroshige and Kuroiwa,2 who showed that the severity of pruritus may reflect the
residual renal function. In addition, the Ca*P, BUN and PTH in pruritic patients was
significantly higher than non-pruritic patients. Similar results were also present in Ho et al.9
and Hiroshige et al.2 This showed that when BUN and PTH are retained in the body, patients
with electrolyte imbalance might easily have pruritus.2, 4, 9
There were still several inconsistent results in the univariate analysis compared with the
previous findings. Concerning dermatological characteristics, there was no statistically
significant relationship between sex and pruritus, as suggested in previous studies.8,
However, the χ2 test of Mistik et al.
19
and Narita et al.
20
21
showed pruritus was more
significant in males than in females. The possible explanation for these findings was that
females usually regularly use emollients for skin care. Skin emollients of aqueous gel
containing high water content could reduce itching, almost completely improving skin
dryness in patients with mild uremic pruritus.22-23
In terms of dialytic characteristics, the method of dialysis was not related to uremic
pruritus, as was also found by Ponticelli and Bencini.24 However, the hemodialytic membrane
was not related to uremic pruritus, which is different to previous studies by Szepietowski et
al.4 and Schouten et al.25 A possible explanation was that all the hemodialytic patients in our
study used non-complement activating membrane for high-flux and high-permeability dialysis.
In the studies by Szepietowski et al.4 and Schouten et al.,25 however, some patients still used
the traditional complement activating membrane. Otherwise, the Kt/Vurea was not significantly
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associated with uremic pruritus in our study, which is the same as results in Chiu et al.21 and
Zucker et al.8 We also found that the average Kt/Vurea in nonpruritic patients was higher than
in pruritic patients with similar results shown by Dyachenko et al.26 This indicated that the
higher Kt/Vurea, the lower opportunity to induce pruritus. Hiroshige and Kuroiwa2 mentioned
that if the average Kt/Vurea was higher than 1.2-1.3, the patient could have effective dialysis
and would not incur pruritus. A similar result was shown by Cohen and Masi27 who thought
that optimal dialysis was achieved when the Kt/Vurea was more than 1.5. A possible
explanation was that with the renal function impairment, the pruritogenic substances will be
retained in the body. The optimal Kt/Vurea could improve the low-molecule substance
exchange of toxins during the dialysis session and therefore decrease the incidence of pruritus.
However, the average Kt/Vurea was higher than 1.5 in our study, which meant that patients
could have adequate dialysis. In this way, there was no significant correlation between
Kt/Vurea and pruritus. In summary, the relationship between Kt/Vurea and pruritus should be
discussed in the future.
In our study, the trait anxiety was not significantly associated with uremic pruritus, but the
average score of trait anxiety in pruritic patients was higher than in nonpruritic patients. The
result revealed that the more anxious personalities were more easily attacked by uremic
pruritus; similar results were also found in the studies by Stangier et al.28 and Aihara et al.29
The possible explanation might be that when patients suffered from anxiety, the skin lesions
might be aggravated. Finally, this study found average waking-up periods during the night for
scratching was once. This result was similar to Zucker et al.,8 which confirmed that pruritus
could affect the sleep of the patients. In other words, scratching might affect the quality of
sleep of the patients.
We discussed the related factors of uremic pruritus in 110 dialytic patients. After
controlling for the other variables, the predictors were the occupation before dialysis, the
types of renal disease, chloride and skin humidity. However, the BUN, PTH, and Ca*P could
not be shown as predictors in our regression model. Compared with the model used in the
study by Narita et al., 20 we had inconsistent findings. It will need more related research to
support this finding. According to our results, some research implications can also be drawn.
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Firstly, the standardized definition of uremic pruritus needed to be clarified for comparing the
results of related researches. Secondly, a long-term study to understand the mechanism of
uremic pruritus and the interaction of influential factors should be conducted. Many variables
were not significant predictors in the multivariate analysis; further study should therefore be
conducted, using expanded samples in the future. Finally, the relationship between emotion
and pruritus needs further study. In terms of practical implications, nurses should teach
patients the importance of a low-phosphate diet to relieve the occurrence of pruritus. At the
same time, the daily records to memorize the frequency and severity of pruritus will be
needed in the future. Simultaneously, nurses should educate patients to use skin emollients to
improve their skin humidity.
References
1.Taiwan Society of Nephrology. The Dialytic Population in Taiwan. http://www. tsn. org. tw/
(accessed on 2008/03/10)
2.Hiroshige K, Kuroiwa A: Uremic pruritus. Int J Artif Organs 1996；19：265-7.
3.Robertson KE, Mueller BA：Uremic pruritus. Am J Health Syst Phar 1996；53：2159-70.
4.Szepietowski JC, Sikora M, Kusztal M, Salomon J, Magott M, Szepietowski T：Uremic
pruritus: a clinical study of maintenance hemodialysis patients. J Dermatol 2002；29：621-7.
5.Balaskas EV, Chu M, Uldall RP, Gupta A, Oreopoulos DG：Pruritus in continuous
ambulatory peritoneal dialysis and hemodialysis patients. Perit Dial Int 1993；13(Suppl 2)：
S527-32.
6.Friga V, Linos A, Linos DA：Is aluminum toxicity responsible for uremic pruritus in chronic
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8.Zucker I, Yosipovitch G, David M, Gafter U, Boner G：Prevalence and characterization of
uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem
for patients with end-stage renal disease. J Am Acad Dermatol 2003；49：842-6.
9.Ho CC, Yeh HT, Chung HM：Uremic pruritus successfully treated with electrical needle
therapy. Acta Nephrol 1997；11：157-60.
10.Moses S：Pruritus. Am Fam Physician 2003；68：1135-42.
11.Gault MH, Longerich LL, Harnett JD, Wesolowski C：Predicting glomerular function from
adjusted serum creatinine. Nephron 1992；62：249-56.
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12.Gotch FA, Sargent JA：A mechanistic analysis of the National Cooperative Dialysis
Study(NCDS). Kidney Int 1985；28：526-34.
13.Becket NM, Inaba KE：Anxiety；in McFarland GK, McFarlane EA (eds)：Nursing
Diagnosis & Intervention, 3rd ed. Mosby, St. Louis, 1997, pp 551-558.
14.Spielberger CD：The effects of anxiety on complex learning and academic achievement；
in Spielberger CD (eds)：Anxiety and Behavior. Academic Press, New York, 1966, pp
361-398.
15.Chung SK, Long CF: The study of revised state and trait anxiety inventory. Psychological
Testing 1984；31：27-36.
16.Schwartz IF, Iaina A：Uremic pruritus. Nephrol Dial Transplant 1999；14：834-9.
17.Duo LJ：Electrical needle therapy of uremic pruritus. Nephron 1987；47：179-83.
18.Hung KY, Shyu RS, Tsai TJ, Chen WY：Viral hepatitis infection should be considered for
evaluating uremic pruritus in continuous ambulatory peritoneal dialysis. Blood Purification
1998；16：147-53.
19.Mistik S, Utas S, Ferahbas A, Tokgoz B, Unsal G, Sahan H：An epidemiology study of
patients with uremic pruritus. J Europ Acad Derm Venereol 2006；20：672-8.
20.Narita I, Alchi B, Omori K, Sato F, Ajiro J, Saga D：Etiology and prognostic significance
of severe uremic pruritus in chronic hemodialysis patients. Kidney int 2006；69：1626-32.
21.Chiu WY, Chang HR, Halim E, Lian JD ：Uremic pruritus in the maintenance of
hemodialysis patients. Acta Nephrol 2003；17：63-8.
22.Okada K, Matsumoto K：Effect of skin care with an emollient containing a high water
content on mild uremic pruritus. Ther Apher Dial 2004；8：419-22.
23.Szepietowski JC, Salomon J：Uremic Pruritus: still an important clinical problem. J Am
Acad Dermatol 2004；51：842-3.
24.Ponticelli C, Bencini PL：Uremic pruritus: a review. Nephron 1992；60：1-5.
25.Schouten WEM, Grooteman MPC, van Houte AJ, Schoorl M, van Limbeek J, Nube MJ：
Effects of dialyser and dialysate on the acute phase reaction in clinical bicarbonate dialysis.
Nephrol Dial Transplant 2000；15：379-84.
26.Dyachenko P, Shustak A, Rozenman D：Hemodialysis-related pruritus and associated
cutaneous manifestations. Int J Dermatol 2006；45：664-7.
27.Cohen EP, Masi CM：Dialysis efficacy and itching in renal failure. Nephron 1992；62：
257-61.
28.Stangier U, Ehlers A, Gieler U：Measuring adjustment to chronic skin disorders: validation
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29.Aihara M, Hariya T, Ichikawa H, Ikezawa Z：A case of atopic dermatitis which showed
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correlation of psychological state and lesions–changes of value of psychological test, skin
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Table 1. The basic characteristics of uremic dialytic patients(N=110)
variables
Demographic characteristics
sex
male
occupation before dialysis
with occupation
current occupation
with occupation
religion
with religion
Disease characteristics
types of renal disease
diabetic nephritis
CGN
occlusive renal disease
lupus nephritis
hypertensive renal disease
unknown renal disease
others renal disease
Dialytic characteristics
dialytic method
peritoneal dialysis
hemodialytic membrane
PMMA
PS
Cellulose acetate
AM-BIO-HX-90
N(%)
pruritus(N=78) non-pruritus(N=32)
N(%)
N(%)
43(39.1)
32(41)
11(34.4)
61(55.5)
48(61.5)
13(40.6)
36(32.7)
27(34.6)
9(28.1)
79(81.8)
61(78.2)＊
18(56.2)
15(13.6)
31(28.2)
3(2.7)
7(6.4)
18(16.4)
27(24.5)
8(10.3)＊
21(26.9)
2(2.6)
3(3.8)
17(21.8)
24(30.8)
7(21.9)
10(31.3)
1(3.1)
4(12.5)
1(3.1)
3(9.4)
9(8.2)
3(3.8)
6(18.8)
76(69.1)
55(70.5)
21(65.6)
11(32.4)
16(47.1)
4(11.8)
3(8.8)
8(34.8)
13(56.6)
1(4.3)
1(4.3)
3(27.3)
3(27.3)
3(27.3)
2(18.2)
footnote:＊:p<0.05; CGN: chronic glomerular nephritis；PMMA: polytmethyl methacrylate ; PS: polysulfone;
AM-BIO-HX-90: the branded of a non-complement activating membrane.
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Table 2. The physiological parameters of uremic dialytic patients(N=110)
pruritus（n=78）
non-pruritus（n=32）
variables
creatinine
Ca*P
PTH
BUN
chloride
skin humidity
hematocrit
phosphate
magnesium
TEWL
triglyceride
total calcium
free calcium
mean
12.10＊
57.79＊
396.84＊
74.68＊
95.6＊
25.79＊
27.45
5.96＊
2.42
14.42
126.85
9.65＊
4.75
SD
mean
SD
2.96
20.88
400.85
20.26
3.88
9.85
3.56
1.98
10.35
47.73
240.85
66.13
98.13
29.18
27.43
5.11
3.39
13.97
192.86
19.98
5.27
7.11
3.22
1.35
0.46
4.19
57.53
1.02
0.56
2.27
13.12
157.72
9.32
4.71
0.42
3.34
109.02
0.80
0.40
footnote:＊:p<0.05; Ca*P: calcium and phosphorus product; PTH: parathyroid hormone;
BUN: blood urea nitrogen; TEWL: transepidermal water loss; SD: standard deviation
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Table 3. Multiple logistic regression model of pruritus in uremic dialytic patients
variable
Odds ratio2
95% confidence interval
Demographic characteristics
occupation before dialysis
Yes Vs. no
religion
Yes Vs. no
4.11＊
1.06-15.94
2.12
0.56-8.00
Disease characteristics
types of renal disease
diabetic nephritis Vs. URD
CGN Vs. URD
0.24
0.30
0.03-1.90
0.05-1.71
0.36
0.08＊
0.01-20.01
0.01-0.95
0.34-117.23
ORD Vs. URD
lupus nephritis Vs. URD
HRD Vs. URD
6.27
0.07＊
other renal disease Vs. URD
pre-dialytic CCR
0.85
physiological parameters
creatinine
Ca*P
PTH
BUN
0.89
1.02
1.01
1.02
0.87＊
0.94＊
chloride
skin humidity
0.01-0.70
0.54-1.34
0.67-1.18
0.97-1.05
1.00-1.02
0.99-1.06
0.75-0.99
0.88-0.99
footnote：＊:p<0.05; URD: unknown renal disease; CGN: chronic glomerular nephritis; ORD: obstructive
renal disease; HRD: hypertensive renal disease; CCR: creatinine clearance rate; Ca*P: calcium and
phosphorus product; PTH: parathyroid hormone; BUN: blood urea nitrogen
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