Uremic Pruritus Characteristics in Hemodialysis Patients with

Chronic Kidney Disease in Relation to Blood Urea Levels and Dialysis

Adequacy at Jakarta Pelabuhan Hospital, Indonesia

Maria Clarissa Wiraputranto

, Oktatika Pratiwi Agustinus

, Tamarachiara Kuntjoro

, Heryanto

Syamsuddin

Halimun Medical Centre Hospital, Halimun Raya St. No.9, Jakarta, Indonesia

Port Medical Centre Hospital, Enggano St. No.10, Jakarta, Indonesia

Kembangan Community Health Centre, Kembangan Raya St. No.52, Jakarta, Indonesia

Division of Dermatovenereology, Jakarta Pelabuhan Hospital, Kramat Jaya St., Jakarta,Indonesia

Keywords: uremic pruritus, chronic kidney disease, hemodialysis, blood urea level, dialysis adequacy

Abstract: Background and objective: Uremic pruritus is one of the distressing symptoms encountered in patients

with chronic kidney disease. It compromises overall quality of life. Factors associated with the severity of

pruritus remains unclear. This study aims to describe and analyze the relationship of blood urea level and

dialysis adequacy to uremic pruritus. Methods: We conducted a cross-sectional study for 3 months at

Jakarta Pelabuhan Hospital, Indonesia. The intensity of uremic pruritus was measured using both visual

analog scale (VAS) and numerical rating scale (NRS). Results: Of the 75 patients completed the study, 30

(40%) had pruritus. There was no significant correlation between uremic pruritus and blood urea level as

well as dialysis adequacy (p>0.05). Conclusion: Our study suggests that blood urea level and dialysis

adequacy do not play a role in pruritus in hemodialysis patients with chronic kidney disease.

1 INTRODUCTION

Uremic pruritus is one of the most frequent

complications found in hemodialysis patients with

chronic kidney disease. The itch of uremic pruritus,

whether localized or disseminated, is debilitating for

the majority of patients. This intractable symptom

could lead to affect patients’ quality of life (Ko et al.,

2013). Fifty to ninety percent of hemodialysis

patients with chronic kidney disease are afflicted with

pruritus (Aⱪca & Taşci, 2014; Al Shafei & Nour,

2016). There are multifactorial factors that could

cause uremic pruritus, in particular, blood urea levels.

Previous studies suggested that uremic pruritus is

significantly correlated with elevated levels of blood

urea (Al Shafei & Nour, 2016). On the contrary, an

effective dialysis has been shown to reduce the

severity of uremic pruritus (Ko et al., 2013).

To the best of our knowledge, there were no

studies in Indonesia reporting the prevalence of

uremic pruritus in hemodialysis patients with chronic

kidney disease as well as its correlation to blood urea

levels and dialysis adequacy. We hence sought to

describe the prevalence and clinical characteristics of

uremic pruritus in hemodialysis patients with chronic

kidney disease in Jakarta Pelabuhan Hospital,

Indonesia. Our research additionally investigates the

associations of blood urea levels and dialysis

adequacy with the severity of uremic pruritus

measured by means of visual analog scale (VAS) and

numerical rating scale (NRS).

2 METHODS

This was an analytical descriptive study of patients

with chronic kidney disease undergoing hemodialysis

treatment at Jakarta Pelabuhan Hospital

Hemodialysis Unit. We conducted a cross-sectional

research commencing from September 27th, 2017

until December 27

, 2017. The inclusion criteria of

our study comprised of age above 18 years, no history

of mental health problems as well as consent to

participate. The study population was obtained using

a consecutive sampling technique and was excluded

if the patient did not give written consent.

Wiraputranto, M., Agustinus, O., Kuntjoro, T. and Syamsuddin, H.

Uremic Pruritus Characteristics in Hemodialysis Patients with Chronic Kidney Disease in Relation to Blood Urea Levels and Dialysis Adequacy at Jakarta Pelabuhan Hospital, Indonesia.

DOI: 10.5220/0008151000680072

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 68-72

ISBN: 978-989-758-494-7

During this 3-month period of study, a total of 76

patients were receiving hemodialysis treatment at the

hospital hemodialysis unit. However, one patient was

excluded because of the patient’s refusal. Thus, 75

patients were included in our final analysis. Subjects

received 3.0 – 5.0 hours of hemodialysis, one to three

times a week using bicarbonate dialysate and heparin

anticoagulant. In case of allergy, we switched heparin

to enoxaparin sodium or parnaparin. The diagnosis of

uremic pruritus was made if patients met one of the

following criteria: appearance of pruritus shortly

before the dialysis treatment or at any time of dialysis

without evidence of any other active causes of

pruritus; a minimum of 3 episodes of troubling

pruritus that appears a couple times in a day and lasts

at least a few minutes during a period of time less than

2 weeks; pruritus appears less frequently than

aforementioned criteria but in a regular pattern in a

period of 6 months (Keithi-Reddy et al., 2007).

We designed a comprehensive questionnaire to

evaluate the clinical characteristics of uremic pruritus

and to assess the dialysis adequacy. In regard to the

measurement of the pruritus severity, we used two

different validated tools, VAS and NRS (Phan et al.,

2012; Reich et al., 2016; Reich et al., 2012). Patients

were asked to point to the 10-cm horizontal line of

VAS that corresponded to the intensity of pruritus

where the starting point (0 cm) indicated no pruritus

and the last point (10 cm) demonstrated the worst

imaginable pruritus. We further asked patients to tell

verbally a NRS score that best reflected their

symptom severity where 0 was no pruritus and 10

represented intolerable pruritus. The laboratory

parameter, blood urea level, was measured before the

beginning of hemodialysis treatment. We applied the

Kt/V ratio (amount of dialysis delivered: K =

clearance of urea, t = time on dialysis, V = estimated

total body water) to measure the adequacy of dialysis;

Kt/V > 1.5 was considered as an effective dialysis (1).

Statistical analysis was performed using IBM SPSS

Statistics software version 23.0 where statistical

significance was defined by a probability level of p <

0.05 (95% confidence interval). Descriptive data

were expressed as a mean ± standard deviation and

percentage. Mann-Whitney-U and t-test were

performed to compare means between pruritic and

non-pruritic patients.

3 RESULT

A total of 75 patients participated in this study.

Patients’ demographic and clinical characteristics, as

well as blood urea levels are summarized in Table 1.

The average age of the patients was 56 ± 12,6 years,

ranging from 33-87 years with 65% being males and

35% being females. In pruritic patients, there were 18

male patients (60%) and 12 female patients (40%).

Table 2 demonstrated the prevalence and uremic

pruritus characteristics. The most frequent pruritus

distributions were the localized areas (77%) consisted

of the back (32%), the head (17%), followed by other

areas including the chest, palm, arm, crotch, waist,

thigh, sole, back of hand, shoulder, stomach, and

elbow. There was no statistically significant

difference in the blood urea levels between pruritic

patients (n = 30, Md = 115.00) and non-pruritic

patients (n = 45, Md = 111.00) according to the

Mann-Whitney-U test (p = 0.669) . Applying the non-

dependent t-test, we found that the means of dialysis

adequacy in 30 patients with uremic pruritus and 45

patients without pruritus were not statistically

significantly different (p = 0.192).

Table 1. Demographic, clinical characteristics, and blood urea levels of the participants

Variables

Pruritic patients Non-pruritic

(n=30) patients (n=45)

Gender Male 18 (60%) 31 (69%)

Female 12 (40%) 14 (31%)

Age (years) 54 ± 13.0 57 ± 12.3

Etiology of chronic kidney disease

Hypertension (HTN) 11 (37%) 19 (42%)

Diabetes mellitus (DM) 5 (17%) 11 (24%)

Kidney stone - 3 (7%)

Polycystic kidney disease 1(3%) 1 (2%)

Idiopathic 3 (10%) 2 (5%)

Others 1 (3%) -

Uremic Pruritus Characteristics in Hemodialysis Patients with Chronic Kidney Disease in Relation to Blood Urea Levels and Dialysis

Adequacy at Jakarta Pelabuhan Hospital, Indonesia

Combined DM with HTN 8 (27%) 7 (16%)

HTN with others 1 (3%) 1 (2%)

HTN with kidney stone - 1 (2%)

Polycystic kidney disease

- -

with others

Duration of

hemodialysis ≤ 3 months 7 (23%) 22 (49%)

>3 months 23 (77%) 23 (51%)

Dialysis adequacy

(Kt/V) 2.3 ± 0.9 2.0 ± 1.1

Dialyzer

membrane Polysulfone 21 (70%) 22 (49%)

Polyarylethersulfone 9 (30%) 23 (51%)

Hemodialysis

acces Continuous 21 (70%) 21 (47%)

Temporary 9 (30%) 24 (53%)

Blood urea levels

112.8 ± 34.5 125.5 ± 58.6

Abbreviation: n: Number of patients, K: clerarance of urea; t: time on dialysis; V; estimated total water

Table 2. Uremic pruritus characteristic in patients with pruritus

Variables Statistics

Uremic pruritus diagnosis

criteria

Apperance of pruritus shortly before the dialysis treatment

or at any time of dialysis without evidence of any other

active causes of pruritus

11 (37%)

A minimum of 3 episodes of troubling pruritus that appears

a couple times in a day and lasts at least a few minutes during

a period of time less than 2 weeks

15 (50%)

Pruritus appears less frequently than aforementioned

criteria but in a regular pattern in a period of 6 months

4 (13%)

Distribution

Generalized

7 (23%)

Localized

23 (77%)

Numerical Rating Scale (NRS) 4,5 ± 2.3

Visual Analog Scale (VAS) 4 ± 2.1

Abbreviation: n: Number of patients

4 DISCUSSION

Uremic pruritus remains a frequent and intractable

symptom encountered in hemodialysis patients with

chronic kidney disease (Ko et al., 2013; Kilic &

Tasci, 2014, Shirazian et al., 2017). There is

inconclusive evidence in terms of the

pathophysiology of this entity. In our study, we found

that there were 40% patients with chronic kidney

disease experiencing uremic pruritus. From this 30

pruritic patients, 18 were males and 12 were females.

From this 30 pruritic patients, 18 were males and 12

were females. The majority of patients who reported

pruritus were those who had already undergone

hemodialysis treatment for more than 3 months

(77%).

Fifteen percent of pruritic patients met the second

diagnosis criteria of uremic pruritus which was a

minimum of 3 episodes of troubling pruritus that

appears a couple times in a day and lasts at least a few

minutes during a period of time less than 2 weeks.

Unlike our study, most of previous studies did not

analyze the prevalence of uremic pruritus specifically

based on the diagnosis criteria of uremic pruritus

according to its time of onset and episode frequency.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

Narita et al reported that blood urea level was

statistically correlated with pruritus severity.

According to Ko et al’s study, dialysis adequacy 1.5

had a significant effect in decreasing the severity of

pruritus. On the other hand, we found a difference in

blood urea levels between pruritic and non-pruritic

groups but it was not statistically significant p > 0.05

(0.669). Our study also showed that there was no

statistical difference regarding dialysis adequacy

(Kt/V) between the two groups (p > 0.05). These

findings could be affected by the small number of

participants in our study.

There were 23 pruritic patients (50%) from a total

of 46 patients who had received hemodialysis

treatment for > 3 months. For 29 other patients who

had undergone hemodialysis for ≤ 3 months, 7 of

them (24%) had pruritus. Until now, the relationship

of dialysis vintage with uremic pruritus was

controversial. Some studies suggested that 3-month

hemodialysis therapy would result in decreased

intensity of pruritus while others reported that a

minimum of 12-month hemodialysis would show

beneficial effect. The most common used pruritus

assessment tools are VAS and NRS attributed to its

high discriminative sensitivity. According to the

study from Reich et al, evaluation with NRS would

result in higher pruritus intensity compared with

VAS. There was only a slight difference of 0.1 – 0.6

points between VAS and NRS assessment but this

was not statistically significant (Reich et al., 2012;

Reich et al., 2016). In our study, the pruritus intensity

in the 30 patients with pruritus was 4 ± 2.1 and 4.5 ±

2.3 for VAS and NRS scores, respectively. With

regard to the distribution of the pruritus, we found

that 77% of the patients had localized pruritic areas

on the back, head, chest and extremities. Our findings

were consistent with data regarding the high variety

of the uremic pruritus distribution with the most

commonly involved areas were back, stomach, hand

and head.

5 CONCLUSION

Taken together, our study demonstrates that there is

no statistically significant correlation between uremic

pruritus and blood urea level or dialysis adequacy.

However, there are some limitations of this study.

First, a small number of participants were involved.

Second, the data on VAS and NRS did not include the

baseline scores before the hemodialysis treatment

started. Therefore, we could not further analyze the

relationship of dialysis adequacy and reduction of

pruritus. Third, our study did not exclude participants

with confounding factors, for instance diabetic and

hepatitis patients. Further research with bigger

sample size and prospective design is necessary to

understand contributing factors in uremic pruritus

development.

ACKNOWLEDGMENT

We would like to express our sincere gratitude to all

the patients who signed the consent forms and

participated in the study. Our thanks are also extended

to Mrs. Dessy Emastari as the Director, M. Syaiful

Huda E., MD as the Chief, and all the staffs of

hemodialysis unit at Jakarta Pelabuhan Hospital for

their continuous help and support

REFERENCES

Aⱪca, N.K., & Taşci, S., 2014. An important problem

among hemodialysis patients: uremic pruritus and

affecting factors. Turkish Nephrology Dialysis

Transplantation, 23(3), pp. 210 – 216.

Al Shafei, N. K., & Nour, A., 2016. Observations on the

Association of Serum histamine, Interleukins and Other

Serum Biochemical Values with Severity of Pruritus in

Chronic Hemodialysis Patients. Journal Nanomedicine

Nanotechnology, 7(1).

Keithi-Reddy, S.R., Patel, T.V., Armstrong, A.W., Sigh,

A.K., 2007. Uremic pruritus. Kidney international, 72,

pp. 373-377.

Kilic, A.N, & Tasci, S., 2014. An Important Problem

Among Hemodialysis Patients: Uremic Pruritus.

Turkish Nephrology Dialysis Transplantation, 23(3),

210-216.

Ko, M. J., Wu, H. Y., Chen, H. Y., Chiu, Y. L., Hsu, S. P.,

Pai, M. F., Ju, Y.Y., Lai, C.F., Lu, H.M., Huang, S.H.,

Yang S.Y., Wen, S. Y., Chiu, H.C., and Jee, S.H., 2013.

Uremic pruritus, dialysis adequacy, and metabolic

profiles in hemodialysis patients: a prospective 5-year

cohort study. PLoS One, 8(8), pp. 71404.

Phan, N. Q., Blome, C., Fritz, F., Gerss, J., Reich, A., Ebata,

T., Augustin, M., Szepietowski, J.C., & Ständer, S.,

2012. Assessment of pruritus intensity: prospective

study on validity and reliability of the visual analogue

scale, numerical rating scale and verbal rating scale in

471 patients with chronic pruritus. Acta dermato-

venereologica, 92(5), pp. 502-507.

Reich, A., Heisig, M., Phan, N. Q., Taneda, K., Takamori,

K., Takeuchi, S., Furue, M., Blome, C., Augustin, M.,

Stander, S., & Szepietowski, J. C., 2012. Visual

analogue scale: evaluation of the instrument for the

assessment of pruritus. Acta dermato-

venereologica, 92(5), pp. 497-501.

Uremic Pruritus Characteristics in Hemodialysis Patients with Chronic Kidney Disease in Relation to Blood Urea Levels and Dialysis

Adequacy at Jakarta Pelabuhan Hospital, Indonesia

Reich, A., Riepe, C., Anastasiadou, Z., Mędrek, K.,

Augustin, M., Szepietowski, J. C., & Ständer, S., 2016.

Itch assessment with visual analogue scale and

numerical rating scale: determination of minimal

clinically important difference in chronic itch. Acta

dermato-venereologica, 96(7), pp.978-980.

Reich, A., Riepe, C., Anastasiadou, Z., Mędrek, K.,

Augustin, M., Szepietowski, J. C., & Ständer, S., 2016.

Itch assessment with visual analogue scale and

numerical rating scale: determination of minimal

clinically important difference in chronic itch. Acta

dermato-venereologica, 96(7), pp. 978-980.

Shirazian, S., Aina, O., Park, Y., Chowdhury, N., Leger, K.,

Hou, L., Miyawaki, N., & Mathur, V.S., 2017. Chronic

kidney disease-associated pruritus: impact on quality of

life and current management challenges. International

Journal of Nephrology and Renovascular Disease, 10,

pp. 11-26.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018