Wathanavasin Wannasit, Thammathiwat Theerachai, Susantitaphong Paweena
Nephrology Unit, Department of Medicine, Charoenkrung Pracharak Hospital, Bangkok Metropolitan Administration, Bangkok, Thailand.
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Kidney Int Rep. 2025 Jun 24;10(9):2991-3005. doi: 10.1016/j.ekir.2025.06.037. eCollection 2025 Sep.
Chronic kidney disease (CKD)-associated pruritus (CKD-aP) is one of the most distressing symptoms of patients with CKD, adversely affecting their quality of life and survival. This study aimed to investigate the efficacy and safety of gamma-aminobutyric acid (GABA) analogues and opioid-based therapies in patients with CKD-aP.
The eligible studies were searched from PubMed, Embase, and Scopus up to January 22, 2025. Only randomized controlled trials (RCTs) that reported the treatment effect on pruritus severity scores were included, focusing on both unidimensional scales and multidimensional scales. The results were synthesized using a random-effect model and provided weighted mean difference (WMD) and relative risk (RR) with a 95% confidence interval (CI).
A total of 27 RCTs involving 2836 patients with CKD-aP were analyzed. Treatment with GABA analogues was associated with significantly greater reductions in 10-cm visual analog scale (VAS) and 5-D itch scores with nonsignificant increased incidence of adverse events (AEs) or adverse drug reactions (ADRs). In addition, opioid receptor-targeting treatments significantly decreased worst itch numeric rating scale (WI-NRS), 5-D itch, Skindex-10, and 100-mm VAS, but showed significantly higher rates of AEs or ADRs, particularly related to gastrointestinal issues, as well as neurological disorders such as sleep disturbances.
Our results suggest that GABA analogues and opioid-based therapies, particularly difelikefalin, have significant potential in alleviating itch intensity and improving the quality of life of patients with CKD-aP. However, opioid-based therapies, especially those involving μ-receptor antagonists such as naltrexone and nalbuphine, are associated with a higher incidence of AEs or ADRs. Given the substantial heterogeneity observed in most of the results, interpretation should be approached with caution.
慢性肾脏病（CKD）相关瘙痒（CKD-aP）是CKD患者最痛苦的症状之一，对其生活质量和生存率产生不利影响。本研究旨在调查γ-氨基丁酸（GABA）类似物和基于阿片类药物的疗法对CKD-aP患者的疗效和安全性。
截至2025年1月22日，从PubMed、Embase和Scopus中检索符合条件的研究。仅纳入报告了对瘙痒严重程度评分治疗效果的随机对照试验（RCT），重点关注单维量表和多维量表。使用随机效应模型对结果进行综合分析，并提供加权平均差（WMD）和相对风险（RR）以及95%置信区间（CI）。
共分析了27项涉及2836例CKD-aP患者的RCT。使用GABA类似物治疗可使10厘米视觉模拟量表（VAS）和5-D瘙痒评分显著降低，不良事件（AE）或药物不良反应（ADR）发生率虽有增加但无统计学意义。此外，靶向阿片受体的治疗可显著降低最严重瘙痒数字评定量表（WI-NRS）、5-D瘙痒、Skindex-10和100毫米VAS，但AE或ADR发生率显著更高，尤其与胃肠道问题以及睡眠障碍等神经紊乱有关。
我们的结果表明，GABA类似物和基于阿片类药物的疗法，特别是地洛非林，在减轻CKD-aP患者的瘙痒强度和改善生活质量方面具有显著潜力。然而，基于阿片类药物的疗法，尤其是那些涉及纳曲酮和纳布啡等μ受体拮抗剂的疗法，与AE或ADR的发生率较高有关。鉴于大多数结果中观察到的显著异质性，解释时应谨慎。
