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Meta-Analysis
. 2020 Dec 7;12(12):CD011393.
doi: 10.1002/14651858.CD011393.pub2.

Interventions for itch in people with advanced chronic kidney disease

Daniel Hercz  1 , Simon H Jiang  2 , Angela C Webster  3   4
Affiliations
Meta-Analysis

Interventions for itch in people with advanced chronic kidney disease

Daniel Hercz et al. Cochrane Database Syst Rev. .

Abstract
in English, Persian

Background: Itch in patients with chronic kidney disease (CKD) is common, often very distressing and associated with depression, reduced quality of life, and increased death. The most common first-line treatment has been the use of antihistamines despite the lack of substantial evidence for its use for uraemic itch. Few recommendations and guidelines exist for treatment.

Objectives: We aimed to determine: 1) the benefits and harms (both absolute and relative) of all topical and systemic interventions for the treatment of uraemic itch, either alone or in combination, when compared with placebo or standard care; and, 2) the dose strength or frequency, stage of kidney disease or method of dialysis used (where applicable) in cases where the effects of these interventions vary depending on co-interventions.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 17 December 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: Randomised controlled trials (RCTs) in adults with CKD stages 4 or 5 comparing treatments (pharmacological, topical, exposure, dialysis modality) for CKD associated itch to either placebo or other established treatments.

Data collection and analysis: Two authors independently abstracted study data and assessed study quality. Data were analysed using a random effects meta-analysis design estimating the relative effects of treatment versus placebo. Estimates of the relative effects between treatments are included where possible. For continuous measures of severity of itch up to three months, mean difference (MD) or standardised mean difference (SMD) were used. When reported, adverse effects were tabulated. The certainty of the evidence was estimated using GRADE.

Main results: Ninety-two RCTs, randomising 4466 participants were included. Fifty-eight studies (3285 participants) provided sufficient data to be meta-analysed. Of these, 30 compared an intervention to a placebo or control. The 10 cm Visual Analogue Scale (VAS) was the dominant instrument utilized for itch reporting and the Duo score was used in a minority of studies. GABA analogues including, gabapentin and pregabalin, reduce itch in patients with CKD (5 studies, 297 participants: 4.95 cm reduction, 95% CI 5.46 to 4.44 lower in VAS compared to placebo; high certainty evidence). Kappa opioid agonists, including nalfurafine also reduced itch in this population (6 studies, 661 participants: 1.05 cm reduction, 95% CI 1.40 to 0.71 lower in VAS compared to placebo; high certainty evidence). Ondansetron had little or no effect on itch scores (3 studies, 183 participants: 0.38 cm reduction, 95% CI 1.04 lower to 0.29 higher in VAS compared to placebo; high certainty evidence). Reduction in the severity of itch was reported with oral montelukast, turmeric, zinc sulfate and topical capsaicin. For all other interventions, the certainty of the evidence was low to moderate, and the interventions had uncertain effects on uraemic pruritus. Six studies have disclosed significant financial support from their respective manufacturers, six were affected by lack of blinding, and 11 studies have 15 participants or less. Older, smaller RCTs often failed to follow intention-to-treat protocols with unexplained dropouts after randomisation. Adverse effects were generally poorly and inconsistently reported across all RCTs. No severe adverse events were reported for any intervention.

Authors' conclusions: The RCTs of this meta-analysis contain a large array of interventions with a diverse set of comparators. For many interventions, trials are sparse. This served to make informative meta-analysis challenging. Of all treatments for uraemic pruritus, gabapentinoids (gabapentin and pregabalin) were the most studied and show the greatest reduction in itch scores. Further RCTs, even of the scale of the largest trials included in this review, are unlikely to significantly change this finding. Kappa-opioid agonists (mainly nalfurafine) also may reduce itch, but indirect comparison suggests a much more modest effect in comparison to GABA analogues. Evidence for oral montelukast, turmeric, zinc sulfate, and topical capsaicin also showed an itch score reduction. However, these reductions were reported in small studies, and warrant further investigation. Ondansetron did not reduce itch. It is somewhat unlikely that a further study of ondansetron will change this result.

پیشینه: خارش در بیماران مبتلا به بیماری مزمن کلیه (chronic kidney disease; CKD) شایع بوده، اغلب بسیار ناراحت کننده است و منجر به افسردگی، کاهش کیفیت زندگی، و افزایش مرگ‌ومیر می‌شود. متداول‌ترین روش درمانی خط اول استفاده از آنتی‌هیستامین‌ها است، هر چند که شواهد اساسی در مورد استفاده از آنها برای خارش اورمیک وجود ندارد. توصیه‌ها و دستورالعمل‌های اندکی برای درمان این وضعیت وجود دارد. اهداف: هدف ما تعیین موارد زیر بود: 1) فواید و مضرات (هم مطلق و هم نسبی) همه مداخلات موضعی و سیستمیک برای درمان خارش اورمیک، چه به تنهایی و چه به صورت ترکیبی، در مقایسه با دارونما (placebo) یا مراقبت‌های استاندارد؛ و، 2) قدرت دوز یا فراوانی آن، مرحله بیماری کلیوی یا روش دیالیز مورد استفاده (در صورت وجود) در مواردی که اثرات این مداخلات بسته به مداخلات همزمان، متفاوت باشند. روش‌های جست‌وجو: ما پایگاه ثبت مطالعات گروه کلیه و پیوند در کاکرین را تا 17 دسامبر 2019 از طریق تماس با متخصص اطلاعات و با استفاده از اصطلاحات جست‌وجوی مرتبط با این مرور، بررسی کردیم. مطالعات موجود در پایگاه‌های ثبت از طریق جست‌وجوها در CENTRAL؛ MEDLINE و EMBASE، مجموعه مقالات کنفرانس‌ها، پورتال جست‌وجوی پایگاه ثبت کارآزمایی‌های بالینی بین‌المللی (International Clinical Trials Register; ICTRP) و ClinicalTrials.gov شناسایی شدند. معیارهای انتخاب: کارآزمایی‌های تصادفی‌سازی و کنترل شده (randomised controlled trials; RCTs) در بزرگسالان مبتلا به مراحل 4 یا 5 از CKD، که به مقایسه درمان (دارویی، موضعی، مواجهه، مدالیتی دیالیز) با دارونما یا سایر درمان‌های اثبات شده برای مدیریت CKD همراه با خارش پرداختند. گردآوری و تجزیه‌وتحلیل داده‌ها: دو نویسنده به‌طور مستقل از هم، داده‌ها را استخراج و محدودیت‌های مطالعه را ارزیابی کردند. داده‌ها با استفاده از یک طرح متاآنالیز اثرات تصادفی و با تخمین تأثیرات نسبی درمان در مقابل دارونما آنالیز شدند. برآوردهای اثرات نسبی بین درمان‌ها، در صورت امکان، گنجانده شدند. برای معیارهای پیوسته شدت خارش تا سه ماه، از تفاوت میانگین (MD) یا تفاوت میانگین استاندارد شده (SMD) استفاده شد. در جایی که عوارض جانبی گزارش شدند، به صورت جدول درآمدند. قطعیت شواهد با استفاده از GRADE ارزیابی شد. نتایج اصلی: نود و دو RCT وارد شدند، که 4466 شرکت‎‌کننده را تصادفی‌‎سازی کردند. پنجاه‌وهشت مطالعه (3285 شرکت‌کننده) داده‌های کافی را برای انجام متاآنالیز فراهم کردند. از این تعداد، 30 مطالعه، مداخله را با دارونما یا کنترل مقایسه كردند. مقیاس 10 سانتی‌متری آنالوگ بصری (Visual Analogue Scale; VAS) ابزاری غالب بود که برای گزارش‌دهی در مورد خارش مورد استفاده قرار گرفت و در تعدادی کمی از مطالعات از امتیاز Duo استفاده شد. آنالوگ‌های GABA شامل، گاباپنتین (gabapentin) و پرگابالین (pregabalin)، باعث کاهش خارش در بیماران مبتلا به CKD می‌شود (5 مطالعه، 297 شرکت‌کننده: کاهش 5.46 سانتی‌متری، 95% CI؛ 5.46 تا 4.44 کمتر در VAS در مقایسه با دارونما؛ شواهد با قطعیت بالا). آگونیست‌های کاپا‐اوپیوئید (kappa‐opioid)، از جمله نالفورافین (nalfurafine) نیز باعث کاهش خارش در این جمعیت شدند (6 مطالعه، 661 شرکت‌کننده: کاهش 1.05 سانتی‌متری، 95% CI؛ 1.40 تا 0.71 کمتر در VAS در مقایسه با دارونما؛ شواهد با قطعیت بالا). اندانسترون (ondansetron) تاثیری اندک یا بدون تاثیر بر نمرات خارش داشت (3 مطالعه، 183 شرکت‌کننده: کاهش 0.38 سانتی‌متری، 95% CI؛ 1.04 کمتر تا 0.29 بیشتر در VAS در مقایسه با دارونما؛ شواهد با قطعیت بالا). کاهش در شدت خارش با تجویز مونته‌لوکاست (montelukast) خوراکی، زردچوبه (turmeric)، سولفات روی (zinc sulfate) و کپسایسین (capsaicin) موضعی گزارش شد. برای تمامی مداخلات دیگر، سطح قطعیت شواهد پائین تا متوسط بود، و مداخلات تأثیرات نامشخصی روی خارش اورمیک بر جای گذاشتند. شش مطالعه دریافت حمایت مالی قابل توجهی را از تولید کنندگان مربوطه اعلام کردند، شش مورد تحت تأثیر عدم‐کورسازی قرار داشتند و 11 مطالعه با حضور 15 شرکت‌کننده یا کمتر انجام شدند. RCTهای قدیمی‌تر و کوچکتر نتوانستند از پروتکل‌های قصد درمان (intention‐to‐treat) تبعیت کنند و اغلب پس از تصادفی‌سازی، با خروج بدون دلیل بیماران از مطالعه روبه‌رو بودند. به‌طور کلی عوارض جانبی در تمام RCTها ضعیف و ناسازگار گزارش شدند. هیچ موردی از حوادث جانبی جدی برای هیچ مداخله‌ای گزارش نشد. نتیجه‌گیری‌های نویسندگان: RCTهای این متاآنالیز شامل مجموعه‌ای وسیع از مداخلات با مجموعه‌ای متنوع از مقایسه‌کننده‌ها هستند. برای بسیاری از مداخلات، تعداد کارآزمایی‌ها اندک بود. این مساله باعث شد که متاآنالیز حاوی اطلاعات مفید، چالش‌برانگیز باشد. از میان تمامی درمان‌های خارش اورمیک، گاباپنتینوئیدها (گاباپنتین و پرگابالین) بیشترین تعداد مطالعه را به خود اختصاص داده و بیشترین کاهش نمرات خارش را نشان دادند. RCTهای بعدی، حتی در مقیاس بزرگترین کارآزمایی‌های موجود در این مرور، بعید است که این یافته را به‌طور قابل توجهی تغییر دهند. آگونیست‌های کاپا‐اوپیوئید (عمدتا نالفورافین) نیز می‌توانند خارش را کاهش دهند، اما مقایسه غیر‐مستقیم، تأثیر بسیار متوسط‌ تری را از آن در مقایسه با آنالوگ‌های GABA نشان می‌دهد. شواهد مربوط به مونته‌لوکاست خوراکی، زردچوبه، سولفات روی، و کپسایسین موضعی نیز بیانگر کاهش نمره خارش هستند. با این حال، این کاهش‌ها در مطالعات کوچک گزارش شده، و انجام تحقیقات بیشتری را لازم می‌داند. اندانسترون خارش را کم نکرد. تا حدودی بعید است که انجام مطالعات بیشتر در مورد اندانسترون این نتیجه را تغییر دهند.

Trial registration: ClinicalTrials.gov NCT02671162 NCT02008864 NCT00494975 NCT02559388 NCT01037595 NCT01114672 NCT02858726 NCT02143648 NCT00745199 NCT00693654 NCT00577967 NCT00793156 NCT01073501 NCT01620580 NCT01660243 NCT01852318 NCT02032537 NCT02432508 NCT01513161 NCT02696499 NCT02747979 NCT03422653 NCT03636269 NCT03576235.

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Conflict of interest statement

  1. Daniel Hercz: none known

  2. Simon H Jiang: none known

  3. Angela C Webster: none known

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: Pharmacological interventions (oral or IV), Outcome 1: Itch
1.2
1.2. Analysis
Comparison 1: Pharmacological interventions (oral or IV), Outcome 2: Itch (dichotomous)
2.1
2.1. Analysis
Comparison 2: Topical interventions, Outcome 1: Itch
3.1
3.1. Analysis
Comparison 3: Oral or IV supplements, Outcome 1: Itch
4.1
4.1. Analysis
Comparison 4: Haemodialysis modality, Outcome 1: Itch
5.1
5.1. Analysis
Comparison 5: Other interventions, Outcome 1: Itch
6.1
6.1. Analysis
Comparison 6: Cross‐over studies with paired data, Outcome 1: Cholestyramine
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Afrasiabifar 2017 {published data only}
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Aliasgharpour 2018 {published data only}
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Carmichael 1988 {published data only}
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Chan 1995 {published data only}
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Chen 2006e {published data only (unpublished sought but not used)}
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Chen 2009 {published data only}
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Cho 1997 {published data only}
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De Marchi 1992 {published data only}
    1. De Marchi S, Cecchin E, Villalta D, Sepiacci G, Santini G, Bartoli E. Effect of erythropoietin therapy on uraemic pruritus [abstract]. Nephrology Dialysis Transplantation 1992;7(7):767. [CENTRAL: CN-00260739]
    1. De Marchi S, Cecchin E, Villalta D, Sepiacci G, Santini G, Bartoli E. Relief of pruritus and decreases in plasma histamine concentrations during erythropoietin therapy in patients with uremia. New England Journal of Medicine 1992;326(15):969-74. [MEDLINE: ] - PubMed
Duque 2005 {published data only (unpublished sought but not used)}
    1. Duque MI, Yosipovitch G, Fleischer AB Jr, Willard J, Freedman BI. Lack of efficacy of tacrolimus ointment 0.1% for treatment of hemodialysis-related pruritus: a randomized, double-blind, vehicle-controlled study. Journal of the American Academy of Dermatology 2005;52(3 Pt 1):519-21. [MEDLINE: ] - PubMed
Durant‐Finn 2008 {published data only}
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Fallahzadeh 2015 {published data only}
    1. Fallahzadeh MK, Faridi P, Sarvestani AK, Sagheb MM, Blondin J, Mohagheghzadeh A, et al. Effect of senna on reduction of uremic pruritus in hemodialysis patients: a randomized double-blind placebo-controlled trial [abstract]. American Journal of Kidney Diseases 2015;65(4):A33. [EMBASE: 71875063]
Feily 2012 {published data only}
    1. Feily A, Dormanesh B, Ghorbani AR, Moosavi Z, Kouchak M, Cheraghian B, et al. Efficacy of topical cromolyn sodium 4% on pruritus in uremic nephrogenic patients: a randomized double-blind study in 60 patients.[Erratum in: Int J Clin Pharmacol Ther. 2013 Nov;51(11):910]. International Journal of Clinical Pharmacology & Therapeutics 2012;50(7):510-3. [MEDLINE: ] - PubMed
Foroutan 2017 {published data only}
    1. Foroutan N, Etminan A, Nikvarz N, Shojai Shahrokh Abadi M. Comparison of pregabalin with doxepin in the management of uremic pruritus: a randomized single blind clinical trial. Hemodialysis International 2017;21(1):63-71. [MEDLINE: ] - PubMed
Ghanei 2012 {published data only}
    1. Ghanei E, Zeinali J, Borghei M, Homayouni M. Efficacy of omega-3 fatty acids supplementation in treatment of uremic pruritus in hemodialysis patients: a double-blind randomized controlled trial. Iranian Red Crescent Medical Journal 2012;14(9):515-22. [MEDLINE: ] - PMC - PubMed
Ghorbani 2012a {published data only}
    1. Ghorbani AR, Feily A, Khalili A, Dormanesh B. Lack of efficacy of topical calcineurin inhibitor pimecrolimus 1% on pruritus of severely uremic patients: a randomized double-blind study in 60 patients. Dermatitis 2012;22(3):167-8. [MEDLINE: ] - PubMed
Ghorbani Birgani 2011 {published data only}
    1. Ghorbani Birgani AR, Khalili A, Zamani L. A comparison between the effect of cromolyn sodium gel 4% and pimecrolimus cream 1% in treatment of pruritus of patients with end stage renal disease. Avicenna Journal of Nursing & Midwifery Care 2011;19(2):11-22.
Gilchrest 1977 {published data only}
    1. Gilchrest BA, Rowe JW, Brown RS, Steinman TI, Arndt KA. Relief of uremic pruritus with ultraviolet phototherapy. New England Journal of Medicine 1977;297(3):136-8. [MEDLINE: ] - PubMed
    1. Gilchrest BA. Ultraviolet phototherapy of uremic pruritus. International Journal of Dermatology 1979;18(9):741-8. [MEDLINE: ] - PubMed
Gilchrest 1979 {published data only (unpublished sought but not used)}
    1. Gilchrest BA, Rowe JW, Brown RS, Steinman TI, Arndt KA. Ultraviolet phototherapy of uremic pruritus. Long-term results and possible mechanism of action. Annals of Internal Medicine 1979;91(1):17-21. [MEDLINE: ] - PubMed
    1. Gilchrest BA. Ultraviolet phototherapy of uremic pruritus. International Journal of Dermatology 1979;18(9):741-8. [MEDLINE: ] - PubMed
Gobo‐Oliveira 2018 {published data only}
    1. Gobo-Oliveira M, Pigari VG, Ogata MS, Miot HA, Ponce D, Abbade LP. Gabapentin versus dexchlorpheniramine as treatment for uremic pruritus: a randomised controlled trial. European Journal of Dermatology 2018;28(4):488-95. [MEDLINE: ] - PubMed
Gunal 2004 {published data only}
    1. Gunal AI, Ozalp G, Yoldas TK, Gunal SY, Kirciman E, Celiker H. Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial. Nephrology Dialysis Transplantation 2004;19(12):3137-9. [MEDLINE: ] - PubMed
Hsu 2009 {published data only}
    1. Hsu MC, Chen HW, Hwu YJ, Chanc CM, Liu CF. Effects of thermal therapy on uremic pruritus and biochemical parameters in patients having haemodialysis. Journal of Advanced Nursing 2009;65(11):2397-408. [MEDLINE: ] - PubMed
Hui 2011 {published data only}
    1. Hui B, Min Z, Cai-lan Y, Gang L. Effect of high-flux dialysis membrane on uremic pruritus and solute clearance of maintenance hemodialysis patients. Journal of Clinical Rehabilitative Tissue Engineering Research 2011;15(29):5493-6. [DOI: 10.3969/j.issn.1673-8225.2011.29.043] - DOI
Jiang 2016 {published data only}
    1. Jiang X, Ji F, Chen Z, Huang Q. Comparison of high-flux hemodialysis with hemodialysis filtration in treatment of uraemic pruritus: a randomized controlled trial. International Urology & Nephrology 2016;48(9):1533-41. [MEDLINE: ] - PubMed
Ko 2011 {published data only}
    1. Ko MJ, Yang JY, Wu HY, Hu FC, Chen SI, Tsai PJ, et al. Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: a randomized controlled trial. British Journal of Dermatology 2011;165(3):633-9. [MEDLINE: ] - PubMed
Kumagai 2010 {published data only}
    1. Kumagai H, Ebata T, Takamori K, Miyasato K, Muramatsu T, Nakamoto H, et al. Efficacy and safety of a novel k-agonist for managing intractable pruritus in dialysis patients. American Journal of Nephrology 2012;36(2):175-83. [MEDLINE: ] - PubMed
    1. Kumagai H, Ebata T, Takamori K, Muramatsu T, Nakamoto H, Suzuki H. Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a phase III, randomized, double-blind, placebo-controlled study. Nephrology Dialysis Transplantation 2010;25(4):1251-7. [MEDLINE: ] - PubMed
Kyriazis 2000 {published data only}
    1. Kyriazis J, Glotsos J. Dialysate calcium concentration of</=1.25 mmol/l: is it effective in suppressing uremic pruritus? Nephron 2000;84(1):85-6. [MEDLINE: ] - PubMed
Legroux‐Crespel 2004 {published data only}
    1. Legroux-Crespel E, Cledes J, Misery L. A comparative study on the effects of naltrexone and loratadine on uremic pruritus. Dermatology 2004;208(4):326-30. [MEDLINE: ] - PubMed
Li 2017a {published data only}
    1. Li WH, Yin YM, Chen H, Wang XD, Yun H, Li H, et al. Curative effect of neutral macroporous resin hemoperfusion on treating hemodialysis patients with refractory uremic pruritus. Medicine 2017;96(12):e6160. [MEDLINE: ] - PMC - PubMed
Lin 2012 {published data only}
    1. Lin TC, Lai YH, Guo SE, Liu CF, Tsai JC, Guo HR, et al. Baby oil therapy for uremic pruritus in haemodialysis patients. Journal of Clinical Nursing 2012;21(1-2):139-48. [MEDLINE: ] - PubMed
Mahmudpour 2017 {published data only}
    1. Mahmudpour M, Rouzbeh J, Jalali QA, Pakfetrat M, Zadegan SE, Sagheb MM. Therapeutic effect of montelukast for treatment of uremic pruritus in hemodialysis patients. Iranian Journal of Kidney Diseases 2017;11(1):50-5. [MEDLINE: ] - PubMed
Makhlough 2010 {published data only}
    1. Makhlough A, Ala S, Haj-Heydari Z, Kashi Z, Bari A. Topical capsaicin therapy for uremic pruritus in patients on hemodialysis.[Erratum in: Iran J Kidney Dis. 2010 Jul;4(3):273 Note: Ala, Shahram [added]; Haj-Heydari, Zohreh [added]; Kashi, Zahra [added]; Bari, Alireza [added]]. Iranian Journal of Kidney Diseases 2010;4(2):137-40. [MEDLINE: ] - PubMed
Mapar 2015 {published data only}
    1. Mapar MA, Pazyar N, Siahpoosh A, Latifi SM, Beladi Mousavi SS, Khazanee A. Comparison of the efficacy and safety of zinc sulfate vs. placebo in the treatment of pruritus of hemodialytic patients: a pilot randomized, triple-blind study. Giornale Italiano di Dermatologia e Venereologia 2015;150(4):351-5. [MEDLINE: ] - PubMed
Marin 2013 {published data only}
    1. Marin AR. Gabapentin therapy for pruritus in automated peritoneal dialysis patients: a randomized controlled trial [abstract no: SA-PO936]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):841A.
Mettang 1997 {published data only}
    1. Mettang T, Thomas S, Kuhlmann U. L-carnitine does not alleviate uremic pruritus in hemodialysis patients. Nephron 1997;75(3):372. [MEDLINE: ] - PubMed
    1. Thomas S, Fischer FP, Mettang T, Pauli-Magnus C, Weber J, Kuhlmann U. Effects of L-carnitine on leukocyte function and viability in hemodialysis patients: a double-blind randomized trial. American Journal of Kidney Diseases 1999;34(4):678-87. [MEDLINE: ] - PubMed
Mirnezami 2013 {published data only}
    1. Mirnezami M. Effect of ondasetron on pruritus in hemodialysis patients. Arak Medical University Journal (AMUJ) 2013;16(3):80-4.
Mohamed 2012 {published data only (unpublished sought but not used)}
    1. Mohamed WA, Zaki FM, Bekhit WH, Sherif IS. Sodium thiosulfate (STS): a new option for hemodialysis patients with uremic pruritus [abstract no: SAP598]. Nephrology Dialysis Transplantation 2012;27(Suppl 2):ii511-2. [EMBASE: 70766834]
Mojgan 2017 {published data only}
    1. Mojgan M, Masoud M, Shahrzad S, Zahra PH, Firouzeh M, Jinoos Z, et al. Pruritus-reducing effects of omega-3 fatty acids in hemodialysis patients [abstract no: P106]. Iranian Journal of Kidney Diseases 2017;11(Suppl 1):7-8. [EMBASE: 616611409]
Murphy 2003 {published data only}75728112
    1. Murphy M, Reaich D, Pai P, Finn P, Carmichael AJ. A randomized, placebo-controlled, double-blind trial of ondansetron in renal itch. British Journal of Dermatology 2003;148(2):314-7. [MEDLINE: ] - PubMed
    1. Murphy MD, Reaich D, Pai P, Finn P, Carmichael AJ. A randomised, placebo-controlled, double-blind trial of ondansetron in renal itch [abstract]. British Journal of Dermatology 2001;145(Suppl 59):20-1. [CENTRAL: CN-00509373] - PubMed
Naghibi 2007 {published data only}
    1. Naghibi M, Nazemian F, Mohammad-Poor A, Morovat-Dar Z, Javidi-Dasht-Bayaz A, Azmoodeh H. The effect of gabapentin on uremic pruritus in hemodialysis patients [abstract no: FP479]. Nephrology Dialysis Transplantation 2007;22(Suppl 6):vi181.
Naini 2007 {published data only}
    1. Naini AE, Harandi AA, Khanbabapour S, Shahidi S, Seirafiyan S, Mohseni M. Gabapentin: a promising drug for the treatment of uremic pruritus. Saudi Journal of Kidney Diseases & Transplantation 2007;18(3):378-81. [MEDLINE: ] - PubMed
    1. Naini AE, Shahidi S, Seirafian S, Atapoor A, Khanbabapoor S, Harandi AA, et al. Gabapentin: a promising treatment for uremic pruritus [abstract no: SP471]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv174.
Najafabadi 2012 {published data only}
    1. Mortazavi M, Faghihi G, Naeini AE, Monghad M, Hosseini SM. Zinc sulfate for the relief of pruritus in patients on maintenance hemodialysis [abstract no: SA590]. NDT Plus 2010;3(Suppl 3):iii241. [EMBASE: 70484056]
    1. Najafabadi MM, Faghihi G, Emami A, Monghad M, Moeenzadeh F, Sharif N, et al. Zinc sulfate for relief of pruritus in patients on maintenance hemodialysis. Therapeutic Apheresis & Dialysis 2012;16(2):142-5. [MEDLINE: ] - PubMed
Nakhaee 2015 {published data only}
    1. Nakhaee S, Nasiri A, Waghei Y, Morshedi J. Comparison of Avena sativa, vinegar, and hydroxyzine for uremic pruritus of hemodialysis patients: a crossover randomized clinical trial. Iranian Journal of Kidney Diseases 2015;9(4):316-22. [MEDLINE: ] - PubMed
Nasrollahi 2007 {published and unpublished data}
    1. Nasrollahi AR, Miladipour A, Ghanei E, Yavari P, Haghverdi F. Montelukast for treatment of refractory pruritus in patients on hemodialysis. Iranian Journal of Kidney Diseases 2007;1(2):73-7. [MEDLINE: ] - PubMed
Nofal 2016 {published data only}
    1. Nofal E, Farag F, Nofal A, Eldesouky F, Alkot R, Abdelkhalik Z. Gabapentin: a promising therapy for uremic pruritus in hemodialysis patients: a randomized-controlled trial and review of literature. Journal of Dermatological Treatment 2016;27(6):515-9. [MEDLINE: ] - PubMed
    1. Solak B, Solak Y. Reply to: Gabapentin: a promising therapy for uremic pruritus in hemodialysis patients: a randomized-controlled trial and review of literature. Journal of Dermatological Treatment 2017;28(3):280. [MEDLINE: ] - PubMed
Noshad 2011 {published data only}
    1. Noshad H. Comparison of gabapentin and antihistamins in treatment of uremic pruritus and its psychological problems [abstract no: P209]. Iranian Journal of Kidney Diseases 2011;5(Suppl 2):27-8. [EMBASE: 70673855]
Omidian 2013 {published data only}
    1. Omidian M, Khazanee A, Yaghoobi R, Ghorbani AR, Pazyar N, Beladimousavi SS, et al. Therapeutic effect of oral nicotinamide on refractory uremic pruritus: a randomized, double-blind study. Saudi Journal of Kidney Diseases & Transplantation 2013;24(5):995-9. [MEDLINE: ] - PubMed
Ozaykan 2001 {published data only}
    1. Ozaykan S, Mansur T, Gunduz S, Guney O. Comparison of ondansetron and cyproheptadine in treatment of uremic pruritus [Uremi kasintisi olan hastalarda ondansetron ve siproheptadinin etkinliginin karsilastirilmasi]. Turkderm Deri Hastaliklari Ve Frengi Arsivi 2001;35(2):130-4. [EMBASE: 2001415704]
Pakfetrat 2014 {published data only}
    1. Pakfetrat M, Basiri F, Malekmakan L, Roozbeh J. Effects of turmeric on uremic pruritus in end stage renal disease patients: a double-blind randomized clinical trial. Journal of Nephrology 2014;27(2):203-7. [EMBASE: 2014347658] - PubMed
Pakfetrat 2018 {published data only}
    1. Pakfetrat M, Malekmakan L, Hashemi N, Tadayon T. Sertraline can reduce the uremic pruritus in hemodialysis patient: A double blind randomized clinical trial from Southern Iran. Hemodialysis International 2018;22(1):103-9. [MEDLINE: ] - PubMed
Pauli‐Magnus 2000 {published data only}
    1. Pauli-Magnus C, Mikus G, Alscher DM, Kirschner T, Nagel W, Gugeler N, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, double-blind, placebo-controlled crossover study. Journal of the American Society of Nephrology 2000;11(3):514-9. [MEDLINE: ] - PubMed
Peck 1996 {published data only}
    1. Peck LW, Monsen ER, Ahmad S. Effect of three sources of long-chain fatty acids on the plasma fatty acid profile, plasma prostaglandin E2 concentrations, and pruritus symptoms in hemodialysis patients. American Journal of Clinical Nutrition 1996;64(2):210-4. [MEDLINE: ] - PubMed
Pederson 1980 {published data only}
    1. Pederson JA, Matter BJ, Czerwinski AW, Llach F. Relief of idiopathic generalized pruritus in dialysis patients treated with activated oral charcoal. Annals of Internal Medicine 1980;93(3):446-8. [MEDLINE: ] - PubMed
Peer 1996 {published and unpublished data}
    1. Peer G, Kivity S, Agami O, Fireman E, Silverberg D, Blum M, et al. Randomised crossover trial of naltrexone in uraemic pruritus. Lancet 1996;348(9041):1552-4. [MEDLINE: ] - PubMed
    1. Peer G, Silverberg DS, Blum M, Kaplan E, Iaina A. Naltrexone (NX) an opiate antagonist relieves pruritus in dialysis patients [abstract]. In: ISN XIII International Congress of Nephrology; 1995 Jul 2-6; Madrid, Spain. 1995:560. [CENTRAL: CN-00509406]
Pour‐Reza‐Gholi 2007 {published data only}
    1. Pour-Reza-Gholi F, Nasrollahi A, Firouzan A, Nasli EE, Farrokhi F. Low-dose doxepin for treatment of pruritus in patients on hemodialysis. Iranian Journal of Kidney Diseases 2007;1(1):34-7. [MEDLINE: ] - PubMed
    1. Pour Reza Gholi F, Reza Nasrollahi A, Nafar M, Firoozan A, Esfahani EN, Farrokhi F. A randomized crossover trial: low-dose doxepin reduces pruritus in dialysis patients [abstract no: MP428]. In: 41st Congress. European Renal Association. European Dialysis and Transplantation Association; 2004 May 15-18; Lisbon, Portugal. 2004:374. [CENTRAL: CN-00509425]
Rad 2017 {published data only}
    1. Rad M, Jaghouri E, Sharifipour F, Rakhshani MH. The effects of cool dialysate on pruritus status during hemodialysis of patients with chronic renal failure: a controlled randomized clinical trial. Iranian Red Crescent Medical Journal 2017;19(1):e34759. [EMBASE: 614362274]
Rivory 1984 {published data only}
    1. Rivory JP, Maheut H. Favorable effect of nicergoline on pruritus in chronic hemodialysis patients. Role of a hyper-alpha-adrenergic system? [Effet favorable de la nicergoline sur le prurit des hemodialyses chroniques. Role de l'hyperalpha-adrenergie?]. Presse Medicale 1984;13(44):2703. [MEDLINE: ] - PubMed
Shariati 2010 {published data only}
    1. Shariati A, Abbasi A, Mojer Lou M, Ghorbani M. Comparison of the effects of oral charcoal capsule with aluminum hydroxide syrup on pruritus in hemodialysis patients. Journal of the Guilan University of Medical Sciences 2010;18(72):22-9.
Sherjeena 2017 {published data only}
    1. Sherjeena PB, Binitha MP, Rajan U, Sreelatha M, Sarita S, Nirmal C, et al. A controlled trial of narrowband ultraviolet B phototherapy for the treatment of uremic pruritus. Indian Journal of Dermatology, Venereology & Leprology 2017;83(2):247-9. [MEDLINE: ] - PubMed
Shirazian 2013 {published data only}
    1. Shirazian S, Kline M, Sakhiya V, Schanler M, Moledina D, Patel C, et al. Longitudinal predictors of uremic pruritus. Journal of Renal Nutrition 2013;23(6):428-31. [MEDLINE: ] - PubMed
    1. Shirazian S, Schanler M, Drakakis J, Miyawaki NB, Fishbane S. The effect of vitamin D insufficiency on uremic pruritis [abstract no: PUB388]. Journal of the American Society of Nephrology 2012;23(Abstract Suppl):982A.
    1. Shirazian S, Schanler M, Shastry S, Dwivedi S, Kumar M, Rice K, et al. The effect of ergocalciferol on uremic pruritus severity: a randomized controlled trial. Journal of Renal Nutrition 2013;23(4):308-14. [MEDLINE: ] - PubMed
Silva 1994 {published data only}
    1. Lugon JR, Silva SR, Viana PC, Lugon NV, Hoette M, Ruzany F. Thalidomide (TH) as a new perspective for the treatment of uremic pruritus (UP): a crossed randomized double-blind trial [abstract no: 14P]. Journal of the American Society of Nephrology 1992;3(3):377. [CENTRAL: CN-00461215]
    1. Silva SR, Viana PC, Lugon NV, Hoette M, Ruzany F, Lugon JR. Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial. Nephron 1994;67(3):270-3. [MEDLINE: ] - PubMed
Silverberg 1977 {published data only}
    1. Silverberg DS, Iaina A, Reisin E, Rotzak R, Eliahou HE. Cholestyramine in uraemic pruritus. BMJ 1977;1(6063):752-3. [MEDLINE: ] - PMC - PubMed
Sja'bani 1997 {published data only}
    1. Sja'bani M, Asdie AH. Effect of erythropoietin on pruritus, anemia and quality of life, in chronic hemodialyzed end stage renal disease patients [abstract]. In: ISN XIII International Congress of Nephrology; 1995 Jul 2-6; Madrid, Spain. 1995:501. [CENTRAL: CN-00509480]
    1. Sja'bani M, Asdie AH. Effect of erythropoietin on pruritus and quality of life in chronic hemodialyzed end stage renal disease patients [abstract]. Journal of Clinical Epidemiology 1997;50(Suppl 1):10S. [CENTRAL: CN-00550491]
Solak 2012 {published data only}
    1. Atalay H, Solak Y, Biyik Z, Gaipov A, Guney F, Turk S. Cross-over, open-label trial of the effects of gabapentin versus pregabalin on painful peripheral neuropathy and health-related quality of life in haemodialysis patients. Clinical Drug Investigation 2013;33(6):401-8. [MEDLINE: ] - PubMed
    1. Biyik Z, Solak Y, Atalay H, Gaipov A, Guney F, Turk S. Gabapentin versus pregabalin in improving sleep quality and depression in hemodialysis patients with peripheral neuropathy: a randomized prospective crossover trial. International Urology & Nephrology 2013;45(3):831-7. [MEDLINE: ] - PubMed
    1. Solak Y, Biyik Z, Atalay H, Gaipov A, Guney F, Turk S, et al. Pregabalin versus gabapentin in the treatment of neuropathic pruritus in maintenance haemodialysis patients: a prospective, crossover study. Nephrology 2012;17(8):710-7. [MEDLINE: ] - PubMed
Spencer 2015 {unpublished data only}
    1. Mathur VS, Spencer RH, Illidge J, Stauffer JW, Munera C, Menzaghi F. Improvement of quality of life in hemodialysis patients with uremic pruritus as measured by the skindex-10 questionnaire: effect of a novel kappa opiod receptor agonist, CR845 [abstract no: TH-PO1040]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):338A.
    1. Spencer R, Mathur VS, Tumlin JA, Stauffer JW, Menzaghi F. CR845, a novel kappa opiod receptor agonist reduces moderate-to-severe pruritus and improves quality of life in chronic kidney disease patients undergoing hemodialysis [abstract no: SA-PO1117]. Journal of the American Society of Nephrology 2015;26(Abstract Suppl):B9.
Spencer 2017 {published data only}
    1. Menzaghi F, Munera C, Oberdick MS, Stauffer JW, Spencer RH. Randomized, placebo-controlled study on the efficacy of CR845 in improving the quality of life of hemodialysis patients with CKD- associated pruritus [abstract no: SA-OR032]. Journal of the American Society of Nephrology 2017;28(Abstract Suppl):80.
    1. Munera C, Vernon MK, Stauffer JW, Spencer RH, Menzaghi F. Psychometric validation and meaningful change threshold of the worst itching intensity numerical rating scale for use in hemodialysis patients with pruritus [abstract]. Journal of Investigative Dermatology 2018;138(5 Suppl 1):S99. [EMBASE: 622252595]
    1. Spencer RH, Munera C, Oberdick MS, Stauffer JW, Menzaghi F. Randomized, placebo-controlled study on the efficacy of CR845 in reducing CKD- associated pruritus in hemodialysis patients [abstract no: FR-PO875]. Journal of the American Society of Nephrology 2017;28(Abstract Suppl):629.
    1. Spencer RH, Munera C, Vernon MK, Stauffer JW, Menzaghi F. Clinically meaningful itch reduction by CR845 an 8-week randomized, placebo-controlled study in hemodialysis patients [abstract no: 280]. American Journal of Kidney Diseases 2018;71(4):585. [EMBASE: 621596159]
Subach 2001 {published data only}
    1. Subach RA, Radabaugh RS, Williams DK, Marx MA. Ondansetron versus diphenhydramine versus placebo for hemodialysis-associated itching [abstract no: A1790]. Journal of the American Society of Nephrology 2001;12(Program & Abstracts):348A. [CENTRAL: CN-00447890]
Suwanpidokkul 2007 {published data only}
    1. Suwanpidokkul P, Chaiprasert A, Supasyndh O, Choovichian P, Luesuthiviboon L. Effects of gabanpentin and loratadine on uremic pruritus in hemodialysis patients: a randomized controlled trial [abstract no: F-PO896]. Journal of the American Society of Nephrology 2007;18(Abstracts):300A.
Tamimi 1999 {published data only}
    1. Tamimi NA, Mikhail AI, Stevens PE. Role of gamma-linolenic acid in uraemic pruritus. Nephron 1999;83(2):170-1. [MEDLINE: ] - PubMed
Tan 1990 {published data only}
    1. Tan CC, Wong KS, Thirumoorthy T, Lee E, Woo K. A randomized, crossover trial of sarna and eurax lotions in the treatment of haemodialysis patients with uraemic pruritus. Journal of Dermatological Treatment 1990;1(5):235-8. [EMBASE: 1991052418]
Tapia 1977 {published data only}
    1. Tapia L, Cheigh JS, David DS, Sullivan JF, Saal S, Reidenberg MM, et al. Pruritus in dialysis patients treated with parenteral lidocaine. New England Journal of Medicine 1977;296(5):261-2. [MEDLINE: ] - PubMed
    1. Tapia L, Cheigh JS, David DS, Sullivan JF, Saal S, Reindenberg MM, et al. Treatment of pruritus in dialysis patients with parenteral lidocaine [abstract]. Kidney International 1976;10(6):527. [CENTRAL: CN-00583216]
Tarng 1996 {published data only}
    1. Tarng DC, Cho YL, Liu HN, Huang TP. Hemodialysis-related pruritus: a double-blind, placebo-controlled, crossover study of capsaicin 0.025% cream. Nephron 1996;72(4):617-22. [MEDLINE: ] - PubMed
Taylor 1983 {published data only}
    1. Taylor R, Taylor AE, Diffey BL, Hindson TC. A placebo-controlled trial of UV-A phototherapy for the treatment of uraemic pruritus. Nephron 1983;33(1):14-6. [MEDLINE: ] - PubMed
Tol 2010 {published data only (unpublished sought but not used)}
    1. Tol H, Atalay H, Guney I, Gokbel H, Altintepe L, Buyukbas S, et al. The effects of gabapentin therapy on pruritus, quality of life, depression and sleep quality in pruritic hemodialysis patients. Trakya Universitesi Tip Fakultesi Dergisi 2010;27(1):1-5. [EMBASE: 2010207038]
TREVITR02 2017 {published data only}
    1. Kumar J, Crawford P, Mathur V, Sciascia T. Nalbuphine ER tablets in hemodialysis patients with severe uremic pruritus: multicenter, randomized, double-blind, placebo-controlled trial [abstract no: 185]. American Journal of Kidney Diseases 2016;67(5):A65. [EMBASE: 72313488]
    1. Mathur VS, Germain MJ, Duncan R, Sciascia T. The rationale for and design of TREVITR02: a multicenter randomized, double-blind, placebo-controlled trial of nalbuphine ER for the treatment of uremic pruritus in hemodialysis patients [abstract no: PUB113]. Journal of the American Society of Nephrology 2015;26(Abstract Suppl):912A.
    1. Mathur VS, Kumar J, Crawford PW, Hait H, Sciascia T, TR02 Study Investigators. A multicenter, randomized, double-blind, placebo-controlled trial of nalbuphine ER tablets for uremic pruritus. American Journal of Nephrology 2017;46(6):450-8. [MEDLINE: ] - PubMed
    1. Mathur VS, Kumar J, Crawford PW, Hait H, Sciascia T. A multicenter, phase2/3 randomized, double-blind, placebo-controlled tiral of nalbuphine ER tablets for the treatment of uremic pruritus: baseline population characteristics [abstract no: TH-PO956]. Journal of the American Society of Nephrology 2015;26(Abstract Suppl):316a.
    1. Mathur VS, Kumar J, Crawford PW, Hait H, Sciascia T. Randomized, double-blind, placebo-controlled, parallel, 3-arm study of safety and anti-pruritic efficacy of nalbuphine HCI ER tablets in hemodialysis patients with uremic pruritus [abstract no: HI-OR07]. Journal of the American Society of Nephrology 2015;26(Abstract Suppl):B2.
van Leusen 1978 {published data only}
    1. Leusen R, Kutsch Lojenga JC, Ruben AT. Is cholestyramine helpful in uraemic pruritus? British Medical Journal 1978;1(6117):918-9. [MEDLINE: ] - PMC - PubMed
Vessal 2010 {published data only}
    1. Vessal G, Sagheb MM, Shilian S, Jafari P, Samani SM. Effect of oral cromolyn sodium on CKD-associated pruritus and serum tryptase level: a double-blind placebo-controlled study. Nephrology Dialysis Transplantation 2010;25(5):1541-7. [MEDLINE: ] - PubMed
Wikstrom 2005 {published data only}
    1. Wikstrom B, Gellert R, Ladefoged SD, Danda Y, Akai M, Ide K, et al. Kappa-opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies. Journal of the American Society of Nephrology 2005;16(12):3742-7. [MEDLINE: ] - PubMed
Yoshimoto‐Furuie 1999 {published data only}
    1. Yoshimoto-Furuie K, Yoshimoto K, Tanaka T, Saima S, Kikuchi Y, Shay J, et al. Effects of oral supplementation with evening primrose oil for six weeks on plasma essential fatty acids and uremic skin symptoms in hemodialysis patients. Nephron 1999;81(2):151-9. [MEDLINE: ] - PubMed
Young 2009 {published data only}
    1. Fleischer AB, Kaur M, Clark A, Yosipovitch G. A controlled comparative study of the efficacy of 1% pramoxine hydrochloride lotion for the treatment of uremic pruritus in adult hemodialysis patients [abstract no: P591]. Journal of the American Academy of Dermatology 2007;56(2):AB63. [CENTRAL: CN-00615966]
    1. Young TA, Patel TS, Camacho F, Clark A, Freedman BI, Kaur M, et al. A pramoxine-based anti-itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients. Journal of Dermatological Treatment 2009;20(2):76-81. [MEDLINE: ] - PubMed
Yue 2015 {published data only}
    1. Yue J, Jiao S, Xiao Y, Ren W, Zhao T, Meng J. Comparison of pregabalin with ondansetron in treatment of uraemic pruritus in dialysis patients: a prospective, randomized, double-blind study. International Journal of Urology & Nephrology 2015;47(1):161-7. [MEDLINE: ] - PubMed
Zhang 2016a {published data only}
    1. Zhang J, Yuan Y, An X, Ouyang C, Ren H, Yang G, et al. Comparison of combined blood purification techniques in treatment of dialysis patients with uraemic pruritus. International Journal of Clinical & Experimental Medicine 2016;9(5):8563-8. [EMBASE: 610545436]

References to studies excluded from this review

Bousquet 1989 {published data only}
    1. Bousquet J, Rivory JP, Maheut M, Michel FB, Mion C. Double-blind, placebo-controlled study of nicergoline in the treatment of pruritus in patients receiving maintenance hemodialysis. Journal of Allergy & Clinical Immunology 1989;83(4):825-8. [MEDLINE: ] - PubMed
Burrai 2014 {published data only}
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Che‐Yi 2005 {published data only}
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CYCLE‐HD 2016 {published data only}11299707
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IRCT2015091010076N6 {published data only}
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Jedras 2003 {published data only}
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Joffe 1985 {published data only}
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Little 1995 {published data only}
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    1. Marquez D, Ramonda C, Lauxmann JE, Romero CA, Vukelic VL, Martinatto C, et al. Uremic pruritus in hemodialysis patients: treatment with desloratidine versus gabapentin. Jornal Brasileiro de Nefrologia 2012;34(2):148-52. [MEDLINE: ] - PubMed
NCT00577967 {published data only}
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NCT00793156 {published data only}
    1. McGuire D. A randomized-withdrawal phase 3 study evaluating the safety and efficacy of oral nalfurafine HCl (AC-820) in subjects on hemodialysis with uremic pruritus (renal itch) (AC120-8231). www.clinicaltrials.gov/show/NCT00793156 (first received 19 November 2008).
NCT01073501 {published data only}
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NCT01620580 {published data only}
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NCT01660243 {published data only}
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NCT01852318 {published data only}
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NCT02032537 {published data only}
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NCT02432508 {published data only}
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Yan 2015 {published data only}
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Zadeh 2015 {published data only}
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Zhang 2011d {published data only}
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References to studies awaiting assessment

Bai 2002 {published data only}
    1. Bai YP, Jia HZ, Zhang LX. Analysis of clinical effect of lifu paste in treating patients of long-term dialysis complicated with cutaneous pruritis. Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi [Chinese Journal of Integrated Traditional & Western Medicine] 2002;22(4):301-2. [MEDLINE: ] - PubMed
NCT01513161 {published data only}
    1. Kim SG. Efficacy and safety study of TRK-820 to treat conventional-treatment-resistant pruritus in patients receiving hemodialysis (TRK-820). www.clinicaltrials.gov/show/NCT01513161 (first received 20 January 2012).
NCT02696499 {published data only}
    1. NCT02696499. Treatment of uremic pruritus with PA101B. www.clinicaltrials.gov/show/NCT02696499 (first received 2 March 2016).
NCT02747979 {published data only}
    1. Yu XQ. The effect and safety of hemodialysis and hemoperfusion on severe renal osteopathy and itching in uremia patients. www.clinicaltrials.gov/show/NCT02747979 (first received 22 April 2016).

References to ongoing studies

ACTRN12614000677606 {published data only}
    1. Holt J, Meyer B. Does evening primrose oil Improve pruritis (itching) in a dialysis population? www.anzctr org au/Trial/Registration/TrialReview.aspx?id=366382 (first received 26 June 2014).
DON'T ITCH 2015 {published data only}13971661
    1. Nevols J. Balneum Plus cream for the treatment of itchy skin in renal patients. www.isrctn.com/ISRCTN13971661 (first received 15 January 2015).
IRCT201311152417N14 {published data only}
    1. Mortazavi M. Effect of omega-3 on pruritus scale in hemodialysis patients. www.en.irct.ir/trial/2125 (first received 3 October 2016).
IRCT2015051411940N3 {published data only}
    1. Hoseini AM. The effect of aloe vera gel on pruritus severity of Hemodialysis patients. www.en.irct.ir/trial/12117 (first received 4 May 2016).
NCT03422653 {published data only}
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NCT03636269 {published data only}
    1. NCT03636269. CR845-CLIN3103: a global study to evaluate the safety and efficacy of CR845 in hemodialysis patients with moderate-to-severe pruritus (KALM-2). www.clinicaltrials.gov/show/nct03636269 (first received 17 August 2018).
SNUG 2019 {published data only}
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References to other published versions of this review

Hercz 2014
    1. Hercz D, Jiang SH, Kapoor T, Webster AC. Interventions for itch in people with advanced chronic kidney disease. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No: CD011393. [DOI: 10.1002/14651858.CD011393] - DOI - PMC - PubMed

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