Rastogi Anjay, Fishbane Steven, Lerma Edgar
UCLA CORE Kidney Program, UCLA Health, David Geffen School of Medicine, Los Angeles, CA, USA.
Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA.
Expert Rev Clin Pharmacol. 2023 May;16(5):387-400. doi: 10.1080/17512433.2023.2197209. Epub 2023 Apr 13.
Chronic kidney disease-associated pruritus (CKD-aP) is often experienced by patients with CKD receiving dialysis. Approximately 40% of hemodialysis patients are 'moderately' to 'extremely bothered' by itching, associated with reduced quality of life, poor sleep quality, and depression as well as worse clinical outcomes, including increased medication use, infections, hospitalizations, and mortality.
This review covers the pathophysiology and treatment landscape of CKD-aP, and the development, clinical efficacy, and safety profile of difelikefalin. We summarize the existing evidence, and discuss both the position of difelikefalin in the treatment pathway and potential future developments.
Difelikefalin is a kappa opioid receptor agonist, with a primary mode of action that is outside of the central nervous system and provides an improved safety profile compared with other opioid agonists, with limited potential for abuse and dependency. Difelikefalin has demonstrated efficacy, tolerability, and safety profile in several large-scale clinical trials in more than 1,400 hemodialysis patients with CKD-aP treated for up to 64 weeks. Difelikefalin is the only approved treatment for CKD-aP in the U.S.A and Europe; other treatments are used off-label, have limited proof of efficacy in large-scale clinical trials in this patient population, and may present an increased risk of toxicity in patients with CKD.
接受透析的慢性肾脏病患者常出现慢性肾脏病相关瘙痒（CKD-aP）。约40%的血液透析患者会受到瘙痒“中度”至“极度困扰”，这与生活质量下降、睡眠质量差、抑郁以及包括用药增加、感染、住院和死亡率增加在内的更差临床结局相关。
本综述涵盖CKD-aP的病理生理学和治疗概况，以及地肤法林的研发、临床疗效和安全性。我们总结现有证据，并讨论地肤法林在治疗路径中的地位以及潜在的未来发展。
地肤法林是一种κ阿片受体激动剂，其主要作用模式位于中枢神经系统之外，与其他阿片类激动剂相比安全性更高，滥用和成瘾潜力有限。地肤法林在超过1400例接受长达64周治疗的CKD-aP血液透析患者的多项大规模临床试验中已证明了疗效、耐受性和安全性。地肤法林是美国和欧洲唯一获批用于治疗CKD-aP的药物；其他治疗为超说明书用药，在该患者群体的大规模临床试验中疗效证据有限，且可能增加CKD患者的毒性风险。
