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Gabapentin and Uremic Pruritus in Hemodialysis Patients
Effat Razeghi a; Delaram Eskandari b; Mohammad Reza Ganji c; Ali Pasha Meysamie d; Mansooreh Togha e;
Patricia Khashayar f
a
Internal Diseases Department (Nephrology), Sina Hospital, Urology Research Center, Tehran University of
Medical Sciences, Tehran, Iran b Internal Diseases Department, Imam Hospital, Garmsar, Iran c Internal
Diseases Department (Nephrology), Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran d
Community Medicine, Tehran University of Medical Sciences, Tehran, Iran e Department of Neurology, Sina
Hospital, Tehran University of Medical Sciences, Tehran, Iran f Research and Development Center, Sina
Hospital, Tehran University of Medical Sciences, Tehran, Iran
Online Publication Date: 01 February 2009
To cite this Article Razeghi, Effat, Eskandari, Delaram, Ganji, Mohammad Reza, Meysamie, Ali Pasha, Togha, Mansooreh and
Khashayar, Patricia(2009)'Gabapentin and Uremic Pruritus in Hemodialysis Patients',Renal Failure,31:2,85 — 90
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2. Renal Failure, 31:85–90, 2009
Copyright © Informa Healthcare USA, Inc.
ISSN: 0886-022X print / 1525-6049 online
DOI: 10.1080/08860220802595476
CLINICAL STUDY
LRNF
Gabapentin and Uremic Pruritus in Hemodialysis Patients
Effat Razeghi
Gabapentin and Uremic Pruritus in Hemodialysis Patients
Internal Diseases Department (Nephrology), Sina Hospital, Urology Research Center, Tehran University of Medical Sciences,
Tehran, Iran
Delaram Eskandari
Internal Diseases Department, Imam Hospital, Garmsar, Iran
Mohammad Reza Ganji
Internal Diseases Department (Nephrology), Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Ali Pasha Meysamie
Downloaded By: [Khashayar, Patricia] At: 08:39 12 February 2009
Community Medicine, Tehran University of Medical Sciences, Tehran, Iran
Mansooreh Togha
Department of Neurology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
Patricia Khashayar
Research and Development Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
periods, respectively. No significant correlation was found
Background. Pruritus is a common and bothersome between age, sex, duration of dialysis, underlying diseases, and
problem in 30–50% of hemodialysis patients. The aim of this systolic and diastolic blood pressures and the gabapentin
study was to determine the effect of gabapentin, 100 mg/three effect. Conclusion. Gabapentin is an effective agent in treating
times a week (after each hemodialysis session), on uremic uremic pruritus.
pruritus. Study design. Patients older than 18 years who had
undergone hemodialysis for more than three months were Keywords gabapentin, hemodialysis, pruritus
enrolled in this double-blind clinical trial. They had experienced
pruritus refractory to antihistamines for at least two weeks. The
patients were assigned to receive gabapentin 100 mg following
hemodialysis for a period of four weeks, and after a washout INTRODUCTION
week, they received the placebo for another four weeks. They
were asked to evaluate the severity of their pruritus using a visual Uremic pruritus is a troubling dermal disorder, sec-
analogue scale (VAS). The reduction of pruritus ≥ 50% was ondary to chronic and progressive renal failure; it disturbs
accepted as the response. Results. The mean pruritus score patients’ sleep and reduces their quality of life.[1,2] More
reached 6.44 ± 8.4 (p < 0.0001), 15 ± 11.2 (p < 0.001), and 81.11 than half of dialysis patients (hemodialysis or peritoneal
± 11.07 (p < 0.001) during gabapentin, washout, and placebo
dialysis) and about 30% of the patients with acute and
chronic renal failure who do not undergo hemodialysis
Received 25 July 2008; revised 24 September 2008; accepted complain about pruritus to some degree.[3]
11 October 2008. Pruritus may have peripheral (dermal or neuropathic),
Address correspondence to Effat Razeghi, MD, Sina Hospital, central (neuropathic, neurological, or psychogenic), or
Urology Research Center, P.O. Box: 11367-46911, Imam Khomeini mixed origins. Uremic pruritus is classified as mixed, and
St., Tehran, Iran; Tel.: +98-21-66716546; Fax: +98-21-66716546; various hypotheses have been formed for justifying its
E-mail: effat162@yahoo.com pathogens; accordingly, several treatments with different
85

3. 86 E. Razeghi et al.
results were suggested based on the hypotheses. However, where K is the dialyzer blood water urea clearance in L per
none of the treatments managed to cure the very disabling hour, t is dialysis session length in hours, and V is the dis-
complication.[4,5] tribution volume of urea in liters), and other laboratory
Gabapentin is an anti-convulsion drug, similar to parameters including Ca, P, Alb, and ipTH were measured
GABA transmitter in its structure. The effectiveness of at four intervals (i.e., one week prior to the treatment, the
gabapentin in controlling convulsions is confirmed by drug administration phase, and the washed out, and pla-
many studies; it has also been demonstrated to be effective cebo phases). All samples were taken from the patients
in treating chronic neuropathic diseases. The suggested before undergoing hemodialysis.
dose for stabilizing the serum level of hemodialysis A technician unaware of the phase the patients were
patients is 200–300 mg following each session of hemodi- in asked them to define the severity of pruritus and the
alysis; doses equal to 100 mg, however, are also proposed, effectiveness of the drug. The median score of pruritus in
aiming at reducing the risk of developing neurotoxicity.[6–8] each interval was considered as the accepted score of pru-
Recent studies have suggested that the effectiveness ritus in that period, and the reduction of pruritus for more
of gabapentin on uremic pruritus by affecting the neural than 50% was accepted as the positive response.
calcium channels.[9,10]
There are not many studies assessing the effect of gaba-
pentin 100 mg on uremic pruritus. As a result, the purpose RESULTS
of the present study was to examine the effect of gabapentin
100 mg on uremic pruritus of hemodialysis patients. Thirty-four ESRD patients undergoing hemodialysis
Downloaded By: [Khashayar, Patricia] At: 08:39 12 February 2009
were enrolled in this study. There were 8 male (23%) and
26 female (77%) patients. The mean age of the patients
MATERIALS AND METHODS was 58.4± 12.5 years ranging between 28 and 73 years.
The underlying diseases leading to ESRD in these patients
This double blind clinical trial was conducted in three are outlined in Table 1.
hemodialysis centers of Tehran in 2006. Patients with a Two of the patients discontinued the treatment and
minimum age of 18 and minimum ESRD duration of three were excluded from the study due to representing the
months, suffering from pruritus for at least two weeks, drug’s side effects (e.g., fatigue, dizziness, and drowsi-
were enrolled in this study. They underwent hemodialysis ness). Another patient withdrew from the study, as he did
three times a week for four hours. They had previous not show any improvement within 10 days after the start
attempts of using antihistamines and moisturizers, neither of the study. Six other patients were also excluded because
of which was reported to be useful. of not being cooperative (i.e., poor compliance to the
The patients had normal hepatic function, and there drug). In other words, the complication and no-response
were no specific underlying diseases intervening with the rate was calculated to be 8.8% (CI 95% = 0–18.4%).
study. Those with skin lesions, metabolic diseases (pro- All patients underwent a complete neurological exam
ducing pruritus), drug allergies, and noncompliant cases before initiating the treatment; 24 out of the 25 patients
were excluded from the study. who completed the study had a positive neurological
After the institutional committee board’s approval, exam. All of these 24 cases had signs of distal symmetric
informed consent was obtained from all patients. They polyneuropathy. Hyporeflexia to areflexia was reported in
were asked to quit using anti-pruritus drugs one week prior 23 cases. Stocking-glove pattern of hypoesthesia was
to the study. reported in all of the 24 studied cases, 20 of which had
Subsequently, all of the patients underwent a com- abnormal response in position and vibration tests. Twelve
plete neurological examination. The patients were trained
to evaluate the severity of their pruritus using a 100 mm
visual analogue scale (VAS). Results between 0–25 were Table 1
considered as low, 25–50 as moderate, 50–75 as high, and The frequency of the underlying diseases leading to
75–100 as severe. ESRD
The patients were given gabapentin 100 mg following Underlying disease Number Percentage (%)
each session of hemodialysis for four weeks at the begin-
ning of the study. They then received the placebo for DM 9 36%
another four weeks. One week was considered the wash- HTN 6 24%
out period between the two treatment phases. Idiopathic 4 16%
Blood pressure, Kt/V (i.e., the volume of plasma Others 3 12%
cleared [Kt] divided by the urea distribution volume [V], DM+HTN 3 12%

4. Gabapentin and Uremic Pruritus in Hemodialysis Patients 87
cases had distal motor weakness. Proximal weakness was
reported in neither of the cases. Moreover, carpal tunnel
syndrome was also reported in one of the cases.
All of the cases eligible for receiving the intervention
had the pruritus score of 100 at the beginning of the study.
Following the prescription of gabapentin, the score
reached 6.44 ± 8.46 (p < 0.001). The mean pruritus score
returned to 15 ± 11.27 (p < 0.001) following the one-week
washout period. After administering the placebo, the pruri-
tus score was calculated to be 81.88 ± 11.06 (p < 0.001).
The pruritus score of the patients during the study period
is presented in Figures 1–3
The mean score of pruritus at the end of gabapentin
therapy, washout period, and placebo therapy were 6.44 ±
8.46 (p < 0.001), 15 ± 11.27 (p < 0.001), and 81.88 ±
Figure 1. The daily mean pruritus score in gabapentin therapy
11.06 (p < 0.001), respectively. There was no meaningful
phase.
relationship between age, gender, the duration of dialysis,
the underlying disease leading to ESRD, and KTV and the
mean score of pruritus in the three phases of the study.
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In the placebo phase, the mean score of pruritus was
lower than the score prior to intervention.
The mean score of pruritus in the three phases of
gabapentin therapy, washout, and placebo was not corre-
lated with the mean albumin serum (p = 0.84, Pearson cor-
relation = 0.4). Moreover, the mean CRP in the three
phases was not correlated with the mean score of pruritus
(p = 0.42; Pearson correlation = 0.166).
Some patients claimed that their pruritus was recov-
ered following the treatment of hyperphosphatemia; how-
ever, despite the high serum levels of phosphate at the
beginning of the study (6.24 ± 2.31), there was no correla-
tion between pruritus and the serum phosphate level. It
should be noted that these patients were often treated in
order to lower the phosphate level; this treatment did not Figure 2. The daily mean pruritus score in placebo phase.
influence the results of our study.
There was no significant relationship between the
patients’ age, sex, duration of dialysis, underlying diseases,
hemoglobin, Ca, P, Alb, P, ipTH, CRP, systolic and diastolic
blood pressures, Kt/V, and the severity of pruritus in the three
phases of gabapentin therapy, washout, and placebo therapy.
The results are demonstrated in Tables 2 and 3.
Complications secondary to drug use was reported in
two of the total 34 patients enrolled in this study. The compli-
cations were limited to dizziness, drowsiness, and unspecified
fatigue; however, because the complications emerged by the
administration of the drug and disappeared by discontinuing
it, the two cases were ethically excluded from the study.
DISCUSSION
Figure 3. The daily mean pruritus score evaluated by the
The etiology and pathogens of uremic pruritus is patients in the three phases of the study (i.e., gabapentin therapy,
not clearly known. Neurological hypothesis,[11,12] the washed out, and placebo).

5. 88 E. Razeghi et al.
Table 2
Variations of the laboratory variables in different intervention phases
Time of measurement
Before starting the End of Gabapentin End of washed-out End of placebo
Variable treatment (phase 0) therapy (phase 1) phase phase
Hb 10.6 ± 1.8 11.1 ± 1.7 10.1 ± 2.6 10.6 ± 1.7
Ca 9.5 ± 2.5 9.2 ± 0.9 9.38 ± 1.1 8.9 ± 2.8
P 6.24 ± 2.31 6.46 ± 2.24 6.78 ± 2.8 6.4 ± 2.4
Alb 4.25 ± 0.6 4.01 ± 0.3 5.45 ± 7.2 4.14 ± 0.5
iPTH 111.12 ± 103 115.57 ± 115.3 120.9 ± 115.5 147.68 ± 179
CRP 11023.3 ± 16630 15354 ± 20077 11249.1 ± 12040 14120.4 ± 16576
Kt/V 1.31 ± 0.2 1.32 ± 0.2 1.35 ± 0.17 1.35 ± 0.17
Table 3 increased sensitivity to itching stimuli. An abnormal ener-
The correlation between the variables and their responsiveness to vation is pointed out in hemodialysis patients.
the treatment (reduction in pruritus) In the present study, all patients were neurologically
Downloaded By: [Khashayar, Patricia] At: 08:39 12 February 2009
examined to compare the treatment results regarding neur-
Mean (at the
opathy findings; but as 24 of the 25 studied patients were
beginning Pearson
Variable of the study) correlation p value* reported to have nearly similar evidences of neurological
problems, further comparison was not performed. The
Age 58.44 ± 12.5 −0.37 0.64 aforementioned evaluation was not conducted in previous
Median dialysis 50 months 0.15 0.4 studies.
duration (25–75) (19.5–36.5) Similar to the previous studies,[21,22] there was no sig-
Kt/V 1.31 ± 0.21 0.1 0.61 nificant correlation between pruritus and the demographic
SBP 113.3 ± 14.1 −0.21 0.3
factors, Kt/V, the duration of dialysis, and the type of renal
DBP 66 ± −7.7 −0.21 0.29
dysfunction in the present study.
Hb 10.6 ± 1.8 0.28 0.16
Ca 9.5 ± 2.5 −0.22 0.91 The results of the present study support the findings
P 6.24 ± 2.31 −0.14 0.48 of a similar study conducted by Maneti et al. in 2005.[10] In
Alb 4.25 ± 0.6 0.4 0.84 another study carried out on 25 hemodialysis patients,
iPTH 111.12 ± 103 0.13 0.52 Gunal et al.[9] showed that the mean score of pruritus in
CRP 11023.3 ± 16630 0.166 0.42 the gabapentin phase was significantly different from that
of the placebo phase.
*Fisher’s z transformation.
We evaluated the relationship of pruritus with inflam-
matory parameters, albumin as a negative phase protein
and CRP as a positive phase protein. Unlike Virga’s
study,[23] no relation was found between the mean score of
intervention of the opioid system,[13,14] the transformed pruritus in the three phases of gabapentin therapy, wash-
metabolism of bi-valence ions,[15–17] hyperparathyroid- out, and placebo and the mean serum albumin level in the
ism,[18,19] and the increase of mast cells and etacoids[18,20] current study. It can be concluded that albumin is influ-
are the most important mechanisms raised. enced by non-inflammatory factors, including nutritional
Neuropathy is prevalent among uremic patients. More status as well as the inflammatory factors.[24] In other
than 65% of the patients with renal failure represent a words, according to that very fact and albumins’ relatively
peripheral nervous disorder,[9] confirming a possible link long half-life, albumin cannot be considered as a proper
between the neurologic origins of uremic pruritus. criterion for evaluating inflammation.
Conduction disorder in sensory-motor pathways is It is noteworthy that the mean CRP in the three phases
one of the most prevalent representations in the initial was not correlated with the mean score of pruritus. This
stages of uremia; it is characterized by paresthesia, prick- was similar to the findings of Virga et al.[23]
ing of the feet, and uneasy foot syndrome.[9] Several previous studies had considered the resistant
Pruritus may also be secondary to a reduction in the and disabling pruritus as a representing sign of hyperthy-
perception threshold. Nerve root damage may lead to an roidism[20,21]; however, many others—including the

6. Gabapentin and Uremic Pruritus in Hemodialysis Patients 89
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