Factors Influencing Pruritus in Uremic Dialysis Patients
Wei-Yun Wang, Kwua-Yun Wang*, Pauling Chu**, Yue-Cune Chang***, Yu-Ying Tang*
Nursing department, Tri-Service General Hospital, Taipei
School of Nursing, National Defense Medical Center, Taipei*
Department of Nephrology, Tri- Service General Hospital, Taipei **
School of Mathematics and Graduate institute of Mathematics, University of Tamkang,
Taiwan***
Correspondence author: Kwua-Yun Wang, 4F, No. 161, Min-Chuan E. Rd. Sec. 6,
Taipei 114, Taiwan, ROC.
Tel: 886-2-87923100 ext. 18766.
Fax: 886-2-8792-3109.
E-mail: W6688@mail.ndmctsgh.edu.tw
國防醫學院護理系
抽印本索取：王桂芸教授
台北市內湖區民權東路 6 段 161 號 4 樓
電話：(02)87923100 轉 18766
傳真：(02)87923109
電子信箱：W6688@mail.ndmctsgh.edu.tw
1
Abstract
Background: Many research studies relate to uremic pruritus, but their results are
inconsistent. The uremic pruritus rate in dialytic patients in Taiwan lies roughly
between 55% and 90%. However, there are rare data available to show the uremic
dialytic pruritus rate in Taiwan. Discussing the related factors and creating a
prediction model was therefore an important issue.
Methods: This study used a cross-sectional study design. 110 patients were recruited
from a medical center in Taiwan. Data were collected by structured questionnaires,
which included demography, disease, dialysis, physiologic parameter, trait anxiety
and pruritic scale. Data were analyzed logistic regression to construct the prediction
model for uremic pruritus.
Results: Results showed that the pruritic incidence rate of uremic dialytic patients
was 70.9%, for patients who received peritoneal dialysis was 72.4% and hemodialysis
was 67.6%. The significant influencing factors for pruritic symptoms among uremic
dialytic patients were the occupation pre-dialysis, types of renal disease, chloride, and
skin humidity.
Conclusion: The skin humidity was the most relevant pruritic symptom. Therefore
we can teach patients to use skin emollients to increase skin humidity and relieve
itching. The optimal goal is to promote the quality of life of uremic dialytic patients.
Key words: uremic dialytic patients, pruritus, influencing factors.
2
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.
3
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
4
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 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.
5
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 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.
6
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
7
(Odds=0.08, 95%C. I.: 0.01-0.95), other renal disease (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).
8
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
9
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 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, 21 However, the χ2 test of Mistik et al. 19 and Narita et al. 20 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
10
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 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
11
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. 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.
12
References
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New York, 1966, pp 361-398.
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14
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.
15
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
16
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
physiological parameters
creatinine
Ca*P
PTH
BUN
chloride
skin humidity
0.85
0.01-0.70
0.54-1.34
0.89
1.02
1.01
0.67-1.18
0.97-1.05
1.00-1.02
1.02
0.87＊
0.94＊
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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摘要
台灣尿毒透析病人搔癢比率介於 55-90%，而針對透析病人搔癢
之研究結果多不一致，故本文欲瞭解影響尿毒透析病人搔癢症之相關
因素及其預測模式。本研究採橫斷式調查研究設計，北市某醫學中心
透析室為研究場所，利用結構式問卷進行資料收集。問卷內容包含人
口學特性、疾病特性、透析因素、生理參數、特質焦慮與皮膚搔癢量
表等，以 SPSS 套裝軟體 15.0 版進行資料處理，採用邏輯式迴歸建構
搔癢症的預測模式。於 110 份問卷結果發現尿毒透析病人搔癢發生機
率為 70.9%，其中腹膜透析者佔 72.4%，行血液透析者發生搔癢的佔
67.6%。而尿毒透析病人目前是否有搔癢之最有力的相關因素包含透
析前職業、腎臟疾病的種類、血氯及皮膚潮濕度。根據此研究結果得
知，尿毒透析病人的皮膚潮濕度與目前是否搔癢有關，因此，應衛教
透析病人使用皮膚潤滑劑，以增加皮膚的潮濕度，減少搔癢症狀的發
生，以增進其生活品質為最終目的。
關鍵字：尿毒透析病人、搔癢症、影響因子。
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