Pathogenesis and Therapy of Chronic Kidney Disease-Associated Itch (Uremic Pruritus)

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 28840

Special Issue Editors


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Guest Editor
Department of Paediatric Nephrology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
Interests: chronic kidney disease; uremic toxins; chronic kidney disease-associated itch; psychosocial; health-related quality of life

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Guest Editor
Department of Dermatology, Venereology and Allergology, Wroclaw Medcial Unieversity, ul. T. Chałubińskiego 1, 50-367 Wroclaw, Poland
Interests: systemic itch; uremic pruritus; itch in dermatoses; skin and psyche
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Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) is a growing problem worldwide, with prevalence of advanced stages (three to five stages) in about 11% of the general population. CKD is associated with numerous complications, with cutaneous ones being considered common. CKD-associated itch, for years also called uremic pruritus, is defined as chronic itch in patients with CKD with advanced stages of renal damage. The diagnosis includes the exclusion of other possible causes. CKD-associated itch is regarded as one of the most bothersome symptoms in patients requiring dialysis treatment. Its prevalence is currently estimated at 40% among dialysis patients. Although described for the first time in 1932, CKD-associated itch is still an unsolved and important clinical challenge. As the pathogenesis is not completely clear, there is no one “gold” treatment available and registered. The pathogenesis of this type of itch is multifactorial, with several factors contributing to the development and/or exacerbation of this sensation. Recently, several studies have been conducted to understand the processes leading to chronic itch in uremic patients in more depth. This resulted in new hypotheses and new treatment targets (within the neural and immune system) for CKD-associated itch. Several new agents specifically aiming to relive CKD-associated itch (e.g., difelikefalin, nalbuphine) are under development. The aim of this Special Issue is to offer a platform, both for clinicians and basic researchers, to present and discuss novel issues in the pathogenesis and treatment of CKD-associated itch. We do hope that all published papers will significantly contribute to a better understanding of CKD-associated itch and will be of benefit for suffering patients in the future.

Prof. Dr. Katarzyna Kilis-Pstrusinska
Prof. Dr. Jacek Szepietowski
Guest Editors

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Keywords

  • Chronic itch
  • Chronic kidney disease-associated itch
  • Etiology
  • Pathogenesis
  • Treatment options
  • Difelikefalin
  • Nalbuphine
  • Anti-interleukin agents.

Published Papers (6 papers)

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Research

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10 pages, 1176 KiB  
Article
Psychosocial Burden of Itch among Renal Transplant Recipients
by Piotr K. Krajewski, Kinga Tyczyńska, Klaudia Bardowska, Piotr Olczyk, Magdalena Krajewska and Jacek C. Szepietowski
Toxins 2022, 14(5), 320; https://doi.org/10.3390/toxins14050320 - 30 Apr 2022
Cited by 6 | Viewed by 1905
Abstract
Itch is the most common symptom of chronic dermatoses. Moreover, itch may be associated with systemic disorders. Chronic kidney disease—associated itch (CKD-aI) may affect up to 20% of renal transplant recipients (RTR). The aim of the study was to assess psychosocial burden of [...] Read more.
Itch is the most common symptom of chronic dermatoses. Moreover, itch may be associated with systemic disorders. Chronic kidney disease—associated itch (CKD-aI) may affect up to 20% of renal transplant recipients (RTR). The aim of the study was to assess psychosocial burden of itch in RTR. The study was performed on a group of 129 RTR, out of which 54 (41.9%) experienced itch in the previous 3 days. A specially designed questionnaire assessing anxiety, depression, stigmatization, and quality of life was used. Results: Patients suffering from itch in the previous 3 days achieved significantly higher scores in GAD-7 (p < 0.001), BDI (p < 0.001), HADS total score (p < 0.001), HADS Depression (p = 0.004), and HADS Anxiety (p < 0.001). Severity of itch correlated positively with HADS, stigmatization scale, and GAD-7. Itch in RTR was associated with higher incidence of depression assessed with BDI (OR 3.7). Moreover, higher prevalence of anxiety was found among patients suffering from CKD-aI, assessed with HADS A and GAD-7 (OR 2.7 and OR 4.8, respectively) The results of our study clearly demonstrate that itch among RTR is a significant burden. Higher prevalence of depression and anxiety in this groups indicate the necessity of addressing itch relief as a part of holistic approach to patients after renal transplantation. Full article
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9 pages, 687 KiB  
Article
The Serum Level of IL-31 in Patients with Chronic Kidney Disease-Associated Pruritus: What Can We Expect?
by Karolina Świerczyńska, Piotr K. Krajewski, Danuta Nowicka-Suszko, Rafał Białynicki-Birula, Magdalena Krajewska and Jacek C. Szepietowski
Toxins 2022, 14(3), 197; https://doi.org/10.3390/toxins14030197 - 7 Mar 2022
Cited by 7 | Viewed by 2644
Abstract
Chronic-kidney-disease-associated pruritus (CKD-aP) is one of the most common and burdensome dermatological symptoms affecting patients undergoing dialysis, and its etiopathogenesis has still not been fully discovered. This study was designed to investigate the possible contribution of interleukin-31 (IL-31) to the pathogenesis of itch [...] Read more.
Chronic-kidney-disease-associated pruritus (CKD-aP) is one of the most common and burdensome dermatological symptoms affecting patients undergoing dialysis, and its etiopathogenesis has still not been fully discovered. This study was designed to investigate the possible contribution of interleukin-31 (IL-31) to the pathogenesis of itch in patients undergoing maintenance hemodialysis (HD). We evaluated the serum level of IL-31 in HD patients with pruritus, in HD patients without pruritus and in healthy controls, as well as its correlation to the severity of itch. The study enrolled 175 adult subjects. The participants were divided into three groups. Group A included 64 patients on maintenance HD with CKD-aP, Group B included 62 patients on maintenance HD not reporting CKD-aP and Group C included 49 healthy controls. Pruritus severity was assessed using the Numerical Rating Scale (NRS), and the serum levels of IL-31 were measured. The results showed that the IL-31 serum level was significantly higher in the itchy group (p < 0.001) in comparison to the patients free from pruritus. Moreover, a marginal trend towards significance (r = 0.242, p = 0.058) was observed between the IL-31 serum level and itch intensity. Our study supports earlier findings on the extended role of IL-31 in the development of CKD-aP. Full article
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14 pages, 2603 KiB  
Article
Clinical Efficacy and Safety of Sodium Thiosulfate in the Treatment of Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials
by Ping-Hsun Lu, Hui-En Chuo, Ko-Lin Kuo, Jian-Fu Liao and Po-Hsuan Lu
Toxins 2021, 13(11), 769; https://doi.org/10.3390/toxins13110769 - 30 Oct 2021
Cited by 5 | Viewed by 3286
Abstract
Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the [...] Read more.
Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = −3.52, 95% confidence interval = −5.63 to −1.41, p = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, p = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease. Full article
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16 pages, 3780 KiB  
Article
Effects of Uremic Clearance Granules in Uremic Pruritus: A Meta-Analysis
by Ping-Hsun Lu, Jen-Yu Wang, Hui-En Chuo and Po-Hsuan Lu
Toxins 2021, 13(10), 702; https://doi.org/10.3390/toxins13100702 - 4 Oct 2021
Cited by 4 | Viewed by 2915
Abstract
Uremic pruritus is common among patients with advanced or end-stage renal disease, with an incidence of >40% among patients on dialysis. Uremic clearance granules (UCGs) are effective in managing uremic pruritus and delay the progression of chronic kidney disease. We conducted a systematic [...] Read more.
Uremic pruritus is common among patients with advanced or end-stage renal disease, with an incidence of >40% among patients on dialysis. Uremic clearance granules (UCGs) are effective in managing uremic pruritus and delay the progression of chronic kidney disease. We conducted a systematic review and a meta-analysis to evaluate the efficacy of UCG in patients with uremic pruritus. Several electronic databases were searched systematically from their inceptions until 19 July 2021. Randomized control trials evaluating the efficacy of UCG in patients with uremic pruritus were selected. Eleven trials including 894 participants were published between 2011 and 2021. Patients administered UCGs had a significantly decreased visual analog scale score (mean difference [MD], −2.02; 95% confidence interval [CI], −2.17 to −1.88), serum levels of hsCRP (MD, −2.07 mg/dL; 95% CI, −2.89 to −1.25; p < 0.00001), TNF-α (MD, −15.23 mg/L; 95% CI, −20.00 to −10.47; p < 0.00001]), β2-MG (MD, −10.18 mg/L; 95% CI, −15.43 to −4.93; p < 0.00001), and IL-6 (MD, −6.13 mg/L; 95% CI, −7.42 to −4.84; p < 0.00001). In addition, UCGs significantly reduced serum levels of creatinine, BUN, PTH, iPTH, phosphorus, and the overall effectiveness rate. UCGs could be an attractive complementary therapy for patients with uremic pruritus. Full article
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Review

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15 pages, 592 KiB  
Review
Chronic Kidney Disease-Associated Pruritus
by Puneet Agarwal, Vinita Garg, Priyanka Karagaiah, Jacek C. Szepietowski, Stephan Grabbe and Mohamad Goldust
Toxins 2021, 13(8), 527; https://doi.org/10.3390/toxins13080527 - 28 Jul 2021
Cited by 30 | Viewed by 10193
Abstract
Pruritus is a distressing condition associated with end-stage renal disease (ESRD), advanced chronic kidney disease (CKD), as well as maintenance dialysis and adversely affects the quality of life (QOL) of these patients. It has been reported to range from 20% to as high [...] Read more.
Pruritus is a distressing condition associated with end-stage renal disease (ESRD), advanced chronic kidney disease (CKD), as well as maintenance dialysis and adversely affects the quality of life (QOL) of these patients. It has been reported to range from 20% to as high as 90%. The mechanism of CKD-associated pruritus (CKD-aP) has not been clearly identified, and many theories have been proposed to explain it. Many risk factors have been found to be associated with CKD-aP. The pruritus in CKD presents with diverse clinical features, and there are no set features to diagnose it.The patients with CKD-aP are mainly treated by nephrologists, primary care doctors, and dermatologists. Many treatments have been tried but nothing has been effective. The search of literature included peer-reviewed articles, including clinical trials and scientific reviews. Literature was identified through March 2021, and references of respective articles and only articles published in the English language were included. Full article
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36 pages, 853 KiB  
Review
Chronic Kidney Disease-Associated Itch (CKD-aI) in Children—A Narrative Review
by Radomir Reszke, Katarzyna Kiliś-Pstrusińska and Jacek C. Szepietowski
Toxins 2021, 13(7), 450; https://doi.org/10.3390/toxins13070450 - 29 Jun 2021
Cited by 8 | Viewed by 6536
Abstract
Chronic kidney disease (CKD) is a condition of widespread epidemiology and serious consequences affecting all organs of the organism and associated with significant mortality. The knowledge on CKD is rapidly evolving, especially concerning adults. Recently, more data is also appearing regarding CKD in [...] Read more.
Chronic kidney disease (CKD) is a condition of widespread epidemiology and serious consequences affecting all organs of the organism and associated with significant mortality. The knowledge on CKD is rapidly evolving, especially concerning adults. Recently, more data is also appearing regarding CKD in children. Chronic itch (CI) is a common symptom appearing due to various underlying dermatological and systemic conditions. CI may also appear in association with CKD and is termed chronic kidney disease-associated itch (CKD-aI). CKD-aI is relatively well-described in the literature concerning adults, yet it also affects children. Unfortunately, the data on paediatric CKD-aI is particularly scarce. This narrative review aims to describe various aspects of CKD-aI with an emphasis on children, based on the available data in this population and the data extrapolated from adults. Its pathogenesis is described in details, focusing on the growing role of uraemic toxins (UTs), as well as immune dysfunction, altered opioid transmission, infectious agents, xerosis, neuropathy and dialysis-associated aspects. Moreover, epidemiological and clinical aspects are reviewed based on the few data on CKD-aI in children, whereas treatment recommendations are proposed as well, based on the literature on CKD-aI in adults and own experience in managing CI in children. Full article
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