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      Uraemic Pruritus: Relief of Itching by Gabapentin and Pregabalin

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          Abstract

          Background: Pruritus (skin irritation or itching) is common in patients with chronic kidney disease (CKD) stages 4 and 5. It is associated with disrupted sleep, reduced quality of life, depression and increased mortality. A video of a patient describing the symptoms is at vimeo.com/49458473. Methods: We used gabapentin or pregabalin in 71 consecutive patients, 82% male. 25 had CKD stage 4 or 5, median eGFR = 17, range 9-30; 40 were on haemodialysis; 6 on peritoneal dialysis. Median itch severity score out of 10 = 8, range 6-10; median duration of itching = 6 months, range 0.5-240. Serum calcium ≤2.60 mmol/l (≤10.4 mg/dl) in 87% patients, phosphate ≤1.8 mmol/l (≤5.6 mg/dl) in 75%. 63% had used antihistamines and not gained relief. Starting dose of gabapentin 100 mg after dialysis or daily. Patients intolerant of gabapentin were offered pregabalin, starting dose 25 mg after dialysis or daily. Results: Gabapentin relieved itching in 47 patients (66%). A video of a patient describing the effect is at vimeo.com/49455976. 26 patients (37%) suffered side effects from gabapentin. Of 21 patients who stopped gabapentin due to side effects, 16 started pregabalin. Pregabalin relieved itching in 13 patients (81%). In total, gabapentin or pregabalin relieved itching in 60 patients (85%), median follow-up 2 months (range 1-8 months). Median itch severity out of 10 reduced from 8 to 1. Conclusions: Gabapentin or pregabalin relieved itching in 85% of 71 consecutively treated CKD patients. Patients should be advised about side effects and the drug initiated at a low dose. Patients intolerant of gabapentin may tolerate pregabalin.

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          A longitudinal study of uremic pruritus in hemodialysis patients.

          Although uremic pruritus (UP) is a highly prevalent complication of chronic kidney disease, it remains poorly characterized. There have been no longitudinal studies of natural history, and no health-related quality of life (HR-QOL) instruments have been developed for UP. The objectives of this study were to describe the natural history of UP, to compare rating scales of itching intensity, and to assess usefulness and validity of HR-QOL instruments for UP. The intensity, severity, and effects of pathologic itching on HR-QOL were assessed prospectively in 103 patients with UP on chronic hemodialysis. Outcome measures were obtained at scheduled intervals over 3.5 months. Itching daily or nearly daily was reported by 84% of patients and had been ongoing for >1 year in 59%. In 83%, pruritus involved large, nondermatomal areas with striking bilateral symmetry. Two thirds of the patients were using medications such as antihistamines, steroids, and various emollients without satisfactory relief of itching. Statistically significant associations were found among itching intensity, severity, and HR-QOL measures in domains such as mood, social relations, and sleep. Among patients with moderate-to-severe UP, changes in itching intensity of 20% or greater were associated with significant reductions in HR-QOL measures. This first longitudinal study of UP describes key features of UP and its effect on HR-QOL. The assessment instruments we have developed are easily used, are responsive to changes in UP intensity, and should facilitate clinical evaluation and research to meet the needs of afflicted patients.
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            Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial.

            Uraemic pruritus is a common and distressing symptom in patients on haemodialysis for chronic renal failure. Gabapentin is an anticonvulsant that alleviates neuropathic pain. We conducted a double-blind, placebo-controlled, crossover study to assess its effectiveness against renal itch. We enrolled in the trial 25 adult patients on haemodialysis who were asked to daily record the severity of their pruritus on a visual analogue scale. The patients were randomly assigned to receive gabapentin for 4 weeks followed by placebo for 4 weeks or the reverse sequence. Gabapentin or placebo were administered thrice weekly, at the end of haemodialysis sessions. The mean pruritus score of the cohort before the study was 8.4 +/- 0.94. After placebo intake, it decreased to 7.6 +/- 2.6 (P = 0.098). The score of four patients decreased by >50% following placebo. After gabapentin administration, the mean score decreased significantly, to 1.2 +/- 1.8 (P = 0.0001), although one patient's symptoms did not improve significantly. No patient dropped out of the study due to adverse effects from gabapentin. Our study shows that gabapentin is safe and effective for treating uraemic pruritus in haemodialysis patients. Our results also support the neuropathic hypothesis of uraemic pruritus.
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              Uraemic pruritus: clinical characteristics, pathophysiology and treatment.

              Pruritus is a common complication of end-stage renal disease (ESRD), affecting about one-third of dialysis patients. It is a chronic, unpleasant symptom with a strong negative impact on patients' quality of life, often inducing sleeplessness and mood disorders. Recent data show that it is also associated with increased mortality. The pathogenesis of uraemic pruritus (UP) is multifactorial. Triggering factors may include uraemia-related abnormalities (particularly involving calcium, phosphorus and parathyroid hormone metabolism), accumulation of uraemic toxins, systemic inflammation, cutaneous xerosis, and common co-morbidities such as diabetes mellitus and viral hepatitis. Recent findings suggest that the neurophysiology of itch is similar to that of pain; this has led to the hypothesis that the two phenomena also closely interact in ESRD patients, who often also experience uraemic neuropathy. The management of UP needs to address several different issues, such as optimization of dialysis efficacy and skin hydration, and correction of calcium-phosphorus metabolism abnormalities. A wide range of antipruritic drugs have been suggested for the treatment of UP, although most of them have only been tested in small, uncontrolled trials, which have yielded conflicting results. Antihistamines are now known to have little or no efficacy, although they are still often prescribed. Novel neurotropic drugs such as gabapentin, along with opioid receptor modulators such as nalfurafine, appear to be effective and well tolerated, but their efficacy has not yet been directly compared. Finally, physical therapies, including UV radiation, may also have a role in patients with refractory symptoms.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2012
                June 2013
                28 March 2013
                : 122
                : 3-4
                : 75-79
                Affiliations
                Heart of England NHS Foundation Trust, Birmingham, UK
                Author notes
                *Dr. Hugh C. Rayner, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham B9 5SS (UK), E-Mail hugh.rayner@heartofengland.nhs.uk
                Article
                349943 Nephron Clin Pract 2012;122:75-79
                10.1159/000349943
                23548570
                bc0151c3-2598-4a81-8950-aab9dde86633
                © 2013 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 27 November 2012
                : 12 February 2013
                Page count
                Tables: 2, Pages: 5
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Gabapentin,Itch,Chronic kidney disease,Pruritus,Pregabalin,Uraemia,Dialysis
                Cardiovascular Medicine, Nephrology
                Gabapentin, Itch, Chronic kidney disease, Pruritus, Pregabalin, Uraemia, Dialysis

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