Search Results (14)

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing symptom that affects both dialysis and non-dialysis patients, significantly impairing their quality of life. Despite its multifactorial pathophysiology, no gold-standard treatment has been established. This review explores various therapeutic options and evaluates their effectiveness based on recent clinical studies and meta-analyses. Therapies targeting novel mechanisms have evolved in recent years. Difelikefalin, a κ-opioid receptor agonist, represents a breakthrough in systemic treatment, demonstrating efficacy with a favorable safety profile. Another opioid-based therapy, nalfurafine, has shown notable symptom relief in multiple clinical studies, with a low risk of abuse. Sertraline, an antidepressant, offers another alternative, although its delayed onset remains a limitation. Nonpharmacologic approaches are also evolving. Phototherapy, particularly UV-B therapy, modulates the immune response, reduces inflammation, and effectively alleviates itching in hemodialysis patients. Personalized treatment strategies are crucial, as responses vary among patients. Further research, including comparative and long-term studies, is essential to refine treatment algorithms and improve patient outcomes. By integrating new pharmacologic and nonpharmacologic options, CKD-aP management is shifting toward a more tailored and effective approach that addresses the individual needs of each patient. Full article

Background: Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in dialysis patients, and is associated with lower quality of life, depression, and sleep problems. CKD-aP is under-recognized and undertreated. While question 20 of the KDQOL is used for CKD-aP assessment in the clinical setting, recent studies testing novel drugs for CKD-aP have used the WI-NRS. Therefore, evaluating the correlation between KDQOL-Q20 and the WI-NRS may enable the identification of patients who could potentially benefit from these treatments. Methods: This was an observational cohort study of patients receiving in-center hemodialysis from the Mount Sinai Kidney Center. Patients completed a baseline survey on CKD-aP (KDQOL-Q20 and WI-NRS), depression, and sleep quality. A repeat survey was conducted at 4 weeks, with the order of the CKD-aP surveys reversed. We defined moderate/severe CKD-aP as a KDQOL-Q20 score ≥2 and a WI-NRS score ≥ 4. Our outcomes of interest were the correlations of KDQOL-Q20 with the WI-NRS, missed HD treatments, depression, and sleep quality. Correlation analysis was performed with Spearman correlation analysis. Association testing between CKD-aP and outcomes was conducted by relative risk estimation with robust error variance. Results: A total of 112 patients completed the study. According to the WI-NRS, 42% of patients reported itching (score of ≥4) while according to KDQOL-Q20, 57% of patients reported itching (score of ≥2). KDQOL-Q20 and the WI-NRS were strongly correlated (r = 0.7; p < 0.001). Patients who had moderate/severe CKD-aP according to KDQOL-Q20 had a non-statistically significant trend towards a lower risk of missed HD treatments and a higher risk of depression, and a statistically significantly higher risk of sleep-related problems, compared to those with no or mild CKD-aP. Conclusions: CKD-aP is a common condition, and is associated with various clinical outcomes. We found a strong correlation between two CKD-aP measures. These results can help to identify patients for CKD-aP treatment. Full article

Worldwide, environmental pollution is a major contributor to illness and mortality, encompassing toxic elements, air pollutants, agricultural pesticides, and contaminated food and water. In patients with end-stage kidney disease, several factors—including impaired renal excretion, the degree of renal impairment, medication use, dialysate contamination, the quality of dialysis water, and metabolic changes—may lead to the accumulation of toxic elements in hemodialysis patients. This study aimed to assess toxic element levels in adults undergoing hemodialysis compared to a control group and to investigate the correlation between parathyroid hormone (PTH) levels, uremic pruritus, anemia and toxic element concentrations. A cross-sectional study was conducted on 60 adult patients undergoing regular hemodialysis for at least three months. Another group of 60 apparently healthy adult voluntaries with matched age and sex with the patient group served as the control. The Inductively Coupled Plasma Mass Spectrometry (ICP-MS) method was used to measure the concentrations of serum levels of aluminum (Al), lead (Pb), cadmium (Cd), chromium (Cr), and arsenic (As) for both groups, as well as in drinking water and dialysate water. The hemodialysis group exhibited significantly higher levels of Al, Pb, Cd, Cr, and As compared to the control group. Serum Pb levels showed a significant negative correlation with PTH, while serum ferritin levels were negatively correlated with Cr. However, no significant correlation was found between toxic element levels and uremic pruritus or anemia. Toxic element concentrations in dialysis and drinking water samples were within acceptable limits and below the detection threshold set by the World Health Organization (WHO) and the Association for the Advancement of Medical Instrumentation/American National Standards Institute (AAMI/ANSI). Therefore, elevated toxic element levels in hemodialysis patients may not be primarily attributable to drinking water or dialysis. Full article

Despite the high burden of fatigue in patients with advanced chronic kidney disease (CKD) stage 4–5 including dialysis, little is known about risk factors and treatments for fatigue. This paper provides an overview of measurement, associated risk factors and approaches to alleviate fatigue. Up to now, the 36-Item Short Form Health Survey (SF-36) is the most widely used tool to measure fatigue. Socio-demographic factors, including older age, female, white ethnicity, less education, unemployment and less social support, are risk factors for fatigue. More severe fatigue is related to anemia, protein energy wasting, inflammation, lactic acidosis, comorbidities (including diabetes, cardiovascular disease and chronic obstructive pulmonary disease), depression, anxiety, sleep disorders and uremic symptoms such as restless legs syndrome and pruritus. Dialysis treatment, dialysis-related low blood pressure and low dialysis adequacy, contribute to fatigue. Medication, such as β-blockers, antidepressant medication and medication for sleep disorders, are associated with fatigue, either as a result of the underlying condition or side effects. Currently, the principal treatments encompass pharmacological and nonpharmacological interventions. The utilization of erythropoiesis-stimulating agent (ESA) for anemia may alleviate fatigue. Physical exercise has been proved to be a promising therapeutic approach. Other potential treatments, such as L-carnitine, sodium bicarbonate, antidepressive medication (such as bupropion), psychological interventions and cold dialysis, require more research. To conclude, further research is needed to better understand the risk factors and underlying mechanism of fatigue, as well as to explore potential treatments for patients with advanced CKD. Full article

(1) Background: Uremic pruritus (UP) is a common and taxing symptom in patients on maintenance hemodialysis (MHD). We have previously shown that blood lead levels (BLLs) and blood aluminum levels (BALs) were separately positively associated with UP in MHD patients. We also found that blood cadmium levels (BCLs) were positively associated with all-cause mortality and cardiovascular-related mortality in MHD patients. We wondered whether there is any correlation between BCLs and UP after adjusting for BLLs and BALs. (2) Methods: Patients enrolled in this study were all from three hemodialysis (HD) centers at Chang Gung Memorial Hospital, Lin-Kou Medical Center, including both the Taipei and Taoyuan branches. Correlations between UP and BLLs, BALs, BCLs, and other clinical data were analyzed. (3) Results: Eight hundred and fifty-three patients were recruited. Univariate logistic regressions showed that diabetes mellitus, hepatitis B virus infection, hepatitis C virus infection, HD duration, hemodiafiltration, dialysis clearance of urea, normalized protein catabolic rate, non-anuria, serum albumin levels, log (intact-parathyroid hormone levels), total serum cholesterol levels, serum low-density lipoprotein levels, log (blood aluminum levels), and log (blood lead levels) were associated with UP. Although log BCLs were not significantly associated with UP (p = 0.136) in univariate analysis, we still included log BCLs in multivariate logistic regression to verify their effect on UP given that our aim in this study was to verify associations between serum heavy metals and UP. Multivariate logistic regressions showed that log BLLs (OR: 27.556, 95% CI: 10.912–69.587, p < 0.001) and log BALs (OR: 5.485, 95% CI: 2.985–10.079, p < 0.001) were positively associated with UP. The other logistic regression, which stratified BLLs and BALs into high and low BLLs and BALs, respectively, showed that high BLLs or high BALs (low BLLs and low BALs as reference) (OR: 3.760, 95% CI: 2.554–5.535, p < 0.001) and high BLLs and high BALs combined (low BLLs and low BALs as reference) (OR: 10.838, 95% CI: 5.381–21.828, p < 0.001) were positively correlated with UP. (4) Conclusions: BLLs and BALs were positively correlated with UP. BCLs were not correlated with UP. Clinicians should pay more attention to the environmental sources of lead and aluminum to prevent UP. Full article

Uremic pruritus is a disturbing and refractory symptom in patients with advanced chronic kidney disease. Chinese herbal medicine has been reported to alleviate uremic pruritus. To investigate the effects of Chinese herbal medicine, we conducted a systematic review and meta-analysis on patients with uremic pruritus. We searched databases (prior to 3 May 2022) for randomized controlled trials on the effects of Chinese herbal medicine in treating uremic pruritus. Our meta-analysis included 3311 patients from 50 randomized controlled trials. In patients with uremic pruritus, adjunctive Chinese herbal medicine significantly improved overall effectiveness (risk ratio 1.29, 95% CI 1.23 to 1.35), quality of life, renal function, reduced pruritus score, and inflammatory biomarkers compared to control groups with hemodialysis alone or with anti-pruritic treatments. Chinese herbal medicine treatment showed a time-dependent tendency in improving the visual analog scale of dialysis patients. Compared to control groups, no significantly higher risk of adverse events in patients taking Chinese herbal medicine (risk ratio 0.60, 95% CI 0.22 to 1.63). Chinese herbal medicine appears to be effective and safe in complementing the treatment of patients with uremic pruritus. Full article

Chronic kidney disease-associated pruritus (CKD-aP) is a chronic condition that significantly reduces the quality of life of patients with end-stage renal disease. The etiology is not fully understood, but imbalance in the activity of the opioid pathways, including downregulation of the kappa-opioid receptor, may contribute to itching sensation. Difelikefalin is a selective, peripherally acting kappa-opioid receptor (KOR) agonist. Recently, difelikefalin has been approved as a first drug for the treatment of pruritus associated with chronic kidney disease (CKD) in adult hemodialysis patients. A systematic review of currently available clinical trials was performed to assess the efficacy and safety of difelikefalin in patients with uremic pruritus. A literature review was conducted in May 2022 based on the PRISMA 2020 guidelines. The analyzed clinical trials showed that difelikefalin was effective in reducing pruritus in patients as assessed by the Worst Itching Intensity Numerical Rating Scale. Improvement in quality of life assessed on the basis of the Skindex score and the 5-D itch scale was also noticed. The most commonly reported side effects were mild and included nausea, vomiting, dizziness, and diarrhea. Due to its proven efficacy and good safety profile, difelikefalin is a promising drug for the treatment of pruritus in patients with chronic kidney disease. Full article

Uremic pruritus, or chronic kidney disease-associated pruritus, is common, bothersome, and sometimes debilitating in patients with chronic kidney disease or end-stage renal disease. Due to its variable clinical manifestations, the diagnosis of uremic pruritus requires exquisite evaluation. Excluding itch resulting from other dermatological causes as well as other systemic conditions is essential for a proper diagnosis. The pathophysiology of uremic pruritus remains uncertain. Hypotheses including toxin deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance are supposed. This review summarizes the way to accurately diagnose uremic pruritus and describes the latest treatment options. Full article

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

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

Pruritus and inflammation associated with accumulation of calcium phosphate (CaP) under the skin are common problems among dialysis patients with chronic kidney disease (CKD). The role of skin commensal microbiota in the CaP-induced uremic pruritus remains uncharacterized. Skin Cutibacterium acnes (C. acnes) can solubilize CaP by the production of short-chain fatty acids (SCFAs), such as butyric acid, through glucose fermentation. Like butyric acid, the N-[2-(2-Butyrylamino-ethoxy)-ethyl]-butyramide (BA-NH-NH-BA), a butyric acid derivative, remarkably induced acetylation of histone H3 lysine 9 (AcH3K9) in keratinocytes. Topical application of fermenting C. acnes, butyric acid or BA-NH-NH-BA onto mouse skin effectively ameliorated CaP-induced skin itching, interleukin (IL)-6 up-regulation in keratinocytes, and extracellular signal-regulated kinase (ERK) 1/2 activation in dorsal root ganglia (DRG). Activation of ERK 1/2 by CaP was markedly reduced in IL-6 knockout mice. Genus Cutibacterium was detected in relatively low abundance in itchy skin of patients with CKD. Our results identify a role for the skin fermenting C. acnes in ameliorating CaP-induced activation of IL-6/p-ERK signaling and resulting skin inflammation. Furthermore, we provide evidence for the potential therapeutic efficacy of BA-NH-NH-BA as a postbiotic for the treatment of uremic pruritus. Full article

Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BK_Ca, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BK_Ca, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8, and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in the expression of ion channels in the skin tissue including, specially cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching. Full article

Background: Chronic pruritus is defined as itch lasting for greater than six weeks. Pruritus is a burdensome manifestation of several internal and external disease states with a significant impact on quality of life. Dupilumab has shown promise in treating a number of conditions including atopic dermatitis (AD) and asthma. Its success in reducing pruritus in AD has generated interest regarding its potential application in other pruritic conditions, such as chronic pruritus of unknown origin, uremic pruritus, and pruigo nodularis. Methods: In this retrospective analysis, we present a series of 20 recalcitrant pruritus patients seen at a tertiary center treated with off-label dupilumab at standard AD dosing. Results: Dupilumab was successful at reducing itch in all treated patients, leading to complete resolution in 12/20 patients and an overall mean NRSi reduction of 7.55. Dupilumab was well tolerated with no significant adverse effects. Conclusions: Our case series suggests dupilumab may be a safe and efficacious therapeutic option in several pruritic conditions and demonstrates the need for further studies to better ascertain its place in the pruritus treatment armamentarium. Full article

Itch is the main chief complaint in patients visiting dermatologic clinics and has the ability to deeply impair life quality. Itch results from activation of cutaneous nerve endings by noxious stimuli such as inflammatory mediators, neurotransmitters and neuropeptides, causing itch signal transduction from peripheral skin, through the spinal cord and thalamus, to the brain cortex. Primarily noninflammatory diseases, such as uremic pruritus, cause itch through certain pruritogens in the skin. In inflammatory skin diseases, atopic dermatitis (AD) is the prototypic disease causing intensive itch by aberrant skin inflammation and epidermal barrier disruption. Recent understanding of disease susceptibility, severity markers, and mechanisms have helped to develop targeted therapy for itch in AD, including monoclonal antibodies against IL-4, IL-13, thymic stromal lymphopoietin (TSLP), IgE and IL-31. Promising effects have been observed in some of them. In this review, we summarized targeted therapies for inflammatory itch in AD and for managing abnormal itch transductions in other common itching skin diseases. Full article