Recent Advances in the Treatment of Uremic Pruritus

Aaron J. Trachtenberg; David Collister; Claudio Rigatto

Disclosures

Curr Opin Nephrol Hypertens. 2020;29(5):465-470. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review: This article provides a focused update on uremic pruritus, highlighting the latest evidence concerning the epidemiology, pathophysiology, and treatment options for this common and bothersome condition.

Recent Findings: Half of dialysis patients and a quarter of those with nondialysis chronic kidney disease experience bothersome itch that reduces quality of life and is increasingly recognized to be associated with poor outcomes including mortality. The KALM-1 trial, which reported effective symptomatic relief with difelikefalin, has bolstered support for the role of an imbalance of μ and κ-opioid receptor activity in pruritogenesis. The role of a chronic inflammatory state, increased cytokine levels and altered immune signaling in pruritogenic nerve activation continues to be elucidated with basic science, which paves the wave for future novel therapeutics. In the meantime, gabapentin appears to be the most evidence-based widely available uremic pruritus treatment, as long as care is taken with dosing and monitoring of side-effects.

Summary: Uremic pruritus remains a top research priority. Patients with uremic pruritus may be able to look forward to a new decade of understanding, knowledge, and novel treatment options for this burdensome condition. As difelikefalin and other potential agents come to market, cost-effectiveness assessments of these interventions will help determine if the widespread use of them is feasible amongst renal programs.

Introduction

Uremic pruritus refers to the common and distressing symptom of persistent itch experienced by many patients with chronic kidney disease (CKD). Pruritus is the most common skin manifestation of kidney disease, affecting both patients with nondialysis CKD and those with kidney failure on dialysis.[1,2] Driving the itch is a complex multifactorial pathophysiology that remains to be fully elucidated but is likely not just uremic in nature.[3,4] For this reason, terms like CKD-associated pruritus or end stage kidney disease (ESKD)-associated chronic itch may be more appropriate.[5,6] However, we use the term uremic pruritus here to be consistent with current usage.

Uremic pruritus refers to persistent itch in a nondermatomal pattern with no primary skin lesion in patients with CKD or kidney failure. Symptoms occur daily or near-daily and can be localized, typically to large symmetric areas of the body, or generalized involving the entire body.[5–8] Uremic pruritus is associated with poor quality of life and poor patient outcomes[1,9] and has been identified as a top research priority by physicians and patients alike.[10] Many interventions have been tried over the years, which our group previously summarized in a systematic review highlighting the paucity of high-quality evidence in this area.[7] There have since been a number of additional literature reviews published on uremic pruritus.[5,6,9,11] There has also been, to our knowledge, the first treatment algorithm and patient information toolkit developed and validated by a multidisciplinary team of experts including patient input.[8] The purpose of this review is to provide the reader with a focused update on uremic pruritus highlighting the latest evidence on the epidemiology, pathophysiology, and treatment options for this common condition.

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