Clinical Efficacy and Safety of Sodium Thiosulfate in the Treatment of Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials

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.

Effects of Uremic Clearance Granules in Uremic Pruritus: A Meta-Analysis

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.

Effects of Thermotherapy on the Quality of Life and Biochemical Parameters in Hemodialysis Patients with Uremic Pruritus

Introduction and objective: Uremic pruritus is a common symptom in patients under hemodialysis. The exact cause of uremic pruritus is not yet known. Although effective treatments are available, there is not still a commonly accepted treatment for this disorder. The present study was aimed at examining the effects of thermotherapy on the quality of life (QOL) and biochemical parameters in hemodialysis patients with uremic pruritus. Patients and methods: In this experimental study, a total of 40 men under hemodialysis suffering from uremic pruritus were randomly selected and divided into an experimental group (thermotherapy) and a control group (no exposure to heat). The experimental group were exposed to far-infrared radiation (FIR) at 40 °C in 15-minute sessions, three times a week, in total for 18 sessions. The Severity of Pruritus Scale (SPS), the Kidney Disease Quality of Life Instrument (KDQOL), and the ItchyQoL were completed by the participants before the start of intervention, one month after the start of intervention, and at the end of intervention. The data were analyzed using SPSS22. Results: Significant differences were observed between the intervention and control groups in all the criteria for assessing uremic pruritus, including history of symptoms, daily activities, QOL, effects on sleep, emotional aspects, and severity of pruritus (p<0.001). In addition, significant improvements were found after the intervention in the criteria for assessing the QOL of the patients (p<0.001). Moreover, improvements in the calcium and phosphorus levels were observed in the intervention group in comparison with the control group. Conclusion: Thermotherapy is effective in reducing the severity of pruritus and increasing the QOL of patents with this problem. Therefore, it can be used as a complementary method in treating patients with uremic pruritus who also experience a reduction in their QOL. Keywords: Hemodialysis, Thermotherapy, Uremic pruritus, Quality of life, Biochemical parameters

The correlation between uremic pruritus and blood lead levels in prevalent hemodialysis patients and its relation to the severity of pruritus using visual analog score

Background Pruritus is a common and often distressing symptom in patients with chronic kidney disease. Though the pathogenesis of uremic pruritus remains poorly understood, systemic inflammation has presented itself as one of the possible explanations. High blood lead levels (BLLs) have been noted to be associated with inflammation and poor nutritional status in hemodialysis patients. Our aim is to study the relation between blood lead levels and uremic pruritus. This is a cross-sectional study that enrolled 50 patients; all were on regular hemodialysis 3 times per week for at least 6 months. Patients were divided into 2 groups, group 1 (n =10) with no pruritus and group 2 (n=40) with varying degrees of pruritus. Group 2 was further divided according to intensity of pruritus by visual analog score (VAS) into mild (n=10), moderate (n=20), and severe pruritus (n=10). Results There was a significant difference in serum lead levels and ferritin levels between groups 1 and 2 (p value < 0.01 and < 0.05, respectively). There was a statistically significant difference in serum lead levels in the groups with varying intensity of pruritus, having higher serum lead levels in patients who exhibited severe pruritus (p value < 0.005) Moreover, a statistically significant relation between elevated blood lead levels and the duration of dialysis was observed in this study. Conclusion Uremic pruritus is a multi-factorial phenomenon, and our study showed that blood lead levels in hemodialysis patients might be associated with increased intensity of pruritus.

The Influence of Peppermint Aromatherapy on Reducing Uremic Pruritus in Patients with Chronic Kidney Disease Undergoing Hemodialysis

Uremic pruritus is one of the chronic renal failure patients’ complaints, which is an uncomfortable and itchy sensation with multifactorial causes. Peppermint complementary therapy is an essential oil with the main component of menthol (50-60%), which provides a cold sensation to the skin. The instrument used in this quasi-experimental study was demographic data and the 5-D itch scale questionnaire. The total sample was 98 participants. The intervention was carried out by administering topical peppermint essential oil. The results showed that the uremic pruritus scale decreased to a mild degree of 51.0%. After being tested by Wilcoxon and Mann-Whitney statistical tests, the intervention group had a p-value of 0.000 &lt;p = 0.05 and in the control group there was a p-value of 0.102 so there was an effect of giving peppermint aromatherapy in reducing uremic pruritus. Peppermint aromatherapy is safe to use and is easy to obtain so, therefore, it can be applied topically to improve coping strategies for patients who experience uremic pruritus.

Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II, randomized, double-blind, placebo-controlled clinical study

Background The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be involved, we conducted a phase II, randomized, controlled study to evaluate nemolizumab (anti-IL-31 receptor A antibody) in Japanese hemodialysis patients with UP. Methods Patients were randomly assigned (1:1:1:1:1) to one of four double-blind groups (receiving a single subcutaneous injection of nemolizumab 0.125, 0.5, or 2.0 mg/kg, or placebo on Day 1) or an open-label reference group (receiving oral nalfurafine hydrochloride 2.5–5 μg once daily for 12 weeks). The primary endpoint was the difference in the absolute change in pruritus visual analog scale (VAS) at Week 4 between placebo and each nemolizumab group. Results The primary efficacy endpoint was not met. The mean change from baseline with all three nemolizumab doses at Week 1, and with 0.5 mg/kg at Week 4, was greater than with placebo. Least square mean differences (95% confidence intervals) in the absolute changes between the placebo arm and each nemolizumab arm were − 2.4 (− 19.7, 14.9) for 0.125 mg/kg, − 8.7 (− 26.6, 9.2) for 0.5 mg/kg, and 0.4 (− 17.0, 17.8) for 2.0 mg/kg. Secondary efficacy parameters including the Shiratori severity score and 5-D itch score failed to show between-group differences. Patients with higher serum IL-31 levels at screening tended to have greater pruritus VAS reductions following nemolizumab treatment. Conclusions In this phase II study in patients with UP, the primary efficacy parameter was not met. Nemolizumab was generally well tolerated with no clinically significant safety concerns. Clinical trial registration JAPIC: JapicCTI-152961, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-152961.

Metabolomic analysis of uremic pruritus in patients on hemodialysis

Pruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that pruritus is caused by solutes that accumulate in the plasma when the kidneys fail. We sought to identify solutes responsible for uremic pruritus using metabolomic analysis to compare the plasma of hemodialysis patients with severe pruritus versus mild/no pruritus. Pruritus severity in hemodialysis patients was assessed using a 100-mm visual analogue scale (VAS), with severe pruritus defined as >70 mm and mild/no pruritus defined as <10 mm. Twelve patients with severe pruritus (Itch) and 24 patients with mild/no pruritus (No Itch) were included. Pre-treatment plasma and plasma ultrafiltrate were analyzed using an established metabolomic platform (Metabolon, Inc.). To identify solutes associated with pruritus, we compared the average peak area of each solute in the Itch patients to that of the No Itch patients using the false discovery rate (q value) and principal component analysis. Dialysis vintage, Kt/Vurea, and serum levels of calcium, phosphorus, PTH, albumin, ferritin, and hemoglobin were similar in the Itch and No Itch patients. Metabolomic analysis identified 1,548 solutes of which 609 were classified as uremic. No difference in the plasma or plasma ultrafiltrate levels of any solute or group of solutes was found between the Itch and No Itch patients. Metabolomic analysis of hemodialysis patients did not reveal any solutes associated with pruritus. A limitation of metabolomic analysis is that the solute of interest may not be included in the metabolomic platform’s chemical library. A role for uremic solutes in pruritus remains to be established.