Yang Hanqi, Pei Ming, Zhai Jingbo, Zhou Zijun, Xing Yunze, Lan Qiumei, Zhu Yixin, Wang Xuchen, Yang Bo
Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Department of Nephrology, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Clin Kidney J. 2025 Jun 23;18(6):sfaf131. doi: 10.1093/ckj/sfaf131. eCollection 2025 Jun.
Uraemic pruritus (UP) is an increasingly significant health burden. However, current treatments are often unsatisfactory and associated with numerous adverse reactions. Recently, several large randomized controlled trials (RCTs) have confirmed that kappa opioid receptor (KOR) agonists, which target the endogenous opioid system, are effective in controlling symptoms. We compared the efficacy and safety of currently available KOR agonists for the treatment of UP.
We conducted a systematic review and network meta-analysis (NMA) of RCTs to assess the efficacy and safety of KOR agonists in patients with UP. The primary outcomes were pruritus-related scales and adverse events. Two independent reviewers evaluated RCTs for eligibility and extracted relevant data, with discrepancies resolved by consensus or a third reviewer. We utilized a fixed effects model within a Bayesian framework for the NMA. Dichotomous variables were presented as risk ratios (RRs) and continuous variables were merged using standardized mean differences. Statistical analyses were performed using R 4.2.3 and JAGS 4.3.0. The risk of bias was assessed using the RoB 2 tool and the certainty of findings was rated according to Grading of Recommendations Assessment, Development and Evaluation criteria. The study protocol was registered on PROSPERO (CRD42020169955).
Ten studies with 2483 participants were included. Concerning the primary endpoints, difelikefalin at doses of 0.25 µg/kg, 0.5 µg/kg, 1.0 µg/kg and 1.5 µg/kg, nalfurafine at 2.5 µg and 5 µg and nalbuphine at 120 mg were significantly effective in reducing itching severity compared with placebo. For the secondary endpoint, all four doses of difelikefalin were associated with higher rates of adverse events compared with placebo, while other interventions showed rates comparable to those of placebo and did not present statistically significant differences.
In summary, difelikefalin at doses of 0.25 µg/kg and 0.5 µg/kg, along with nalfurafine at 0.25 µg/kg and 0.5 µg/kg, can be considered recommended therapeutic options for UP treatment.
尿毒症瘙痒（UP）是一个日益严重的健康负担。然而，目前的治疗方法往往不尽人意，且伴有许多不良反应。最近，几项大型随机对照试验（RCT）证实，靶向内源性阿片系统的κ阿片受体（KOR）激动剂在控制症状方面有效。我们比较了目前可用的KOR激动剂治疗UP的疗效和安全性。
我们对RCT进行了系统评价和网络荟萃分析（NMA），以评估KOR激动剂在UP患者中的疗效和安全性。主要结局是瘙痒相关量表和不良事件。两名独立的审阅者评估RCT的 eligibility 并提取相关数据，如有差异则通过共识或第三位审阅者解决。我们在贝叶斯框架内使用固定效应模型进行NMA。二分变量以风险比（RRs）表示，连续变量使用标准化均差合并。使用R 4.2.3和JAGS 4.3.0进行统计分析。使用RoB 2工具评估偏倚风险，并根据推荐评估、制定和评价标准对研究结果的确定性进行评级。研究方案已在PROSPERO（CRD42020169955）上注册。
纳入了10项研究，共2483名参与者。关于主要终点，与安慰剂相比，剂量为0.25µg/kg、0.5µg/kg、1.0µg/kg和1.5µg/kg的地洛啡肽、2.5µg和5µg的纳呋拉啡以及120mg的纳布啡在减轻瘙痒严重程度方面显著有效。对于次要终点，与安慰剂相比，所有四剂地洛啡肽的不良事件发生率更高，而其他干预措施的发生率与安慰剂相当，且无统计学显著差异。
总之，0.25µg/kg和0.5µg/kg剂量的地洛啡肽，以及0.25µg/kg和0.5µg/kg的纳呋拉啡，可被视为UP治疗的推荐治疗选择。
