Pruritus in Chronic Kidney Disease

Nupur N. Uppal; Antonio Corona; Steven Fishbane

Disclosures

Curr Opin Nephrol Hypertens. 2022;31(5):435-441. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review: Among the many difficult symptoms that patients with kidney disease experience, pruritus is one of the most frequent and troubling. Because a substantial amount of new information has accumulated, we seek here to review the subject.

Recent Findings: Pruritus is not only a common problematic symptom among patients with kidney disease, but its considerably more frequent than nephrologists recognize. The result for patients is not just uncomfortable itch but degraded quality of life as well. The pathogenesis is increasingly understood, but many aspects remain to be fully resolved. Importantly, research is progressing on treatment, leading to the first approved medication in the United States, difelikefalin, in August, 2021.

Summary: As nephrology is progressing to a greater focus on patient symptoms, recognition of the importance of pruritus has led to increased interest and improved diagnosis and treatment options.

Introduction

Chronic kidney disease-associated pruritus (CKD-aP), is defined as itching directly related to kidney disease in the absence of an alternative cause that can cause itching.[1] The largest dataset on prevalence of CKD-aP in patients with CKD, not yet on dialysis, comes from the CKD Outcomes and Practice Patterns Study.[2] In this population with CKD stage 3–5, prevalence of moderate pruritus was 24% in Brazil, 29% in the United States, and 23% in France, and that of severe to extreme pruritus was 11, 13, and 10% in Brazil, United States, and France, respectively. A recent meta-analysis that included 42 studies with adult dialysis patients reported the pooled prevalence of CKD-aP to be 55 and 56% in patients on hemodialysis and peritoneal dialysis, respectively.[3] In Phase 5 of the Dialysis Outcomes and Practice Patterns Study (DOPPS), 37% of patients on hemodialysis reported to be at least moderately bothered by itching, and 18% were very much or extremely bothered by itching.[4] Significantly, it has also been observed that CKD-aP may persist even after kidney transplantation, with a prevalence rate of 12% post transplantation.[5]

CKD-aP can be a debilitating condition that impairs health-related quality of life (HRQOL) and has been associated with increased morbidity, risk of hospitalization, and mortality.[6,7] HRQOL domains such as mood, depression, social relations, and quality of sleep may be impacted.[8,9] Patients with CKD-aP may also be more likely to have restless legs, feel drained[10] and miss more hemodialysis sessions.[11] In addition, patients with severe CKD-aP have a significantly worse overall prognosis than patients with less severe CKD-aP, even after adjusting for other factors, including diabetes mellitus, age, β2-microglobulin, and albumin.[12]

The presentation of CKD-aP is highly diverse. It may occur intermittently or can be persistently present.[4] Although reported to be most symptomatic at night,[13] it may occur before, during or after dialysis.[4] CKD-aP does not exhibit a dermatomal pattern and can be generalized in up to 50% of patients[14] or can also have a localized distribution.[1] Patients usually do not exhibit any visible skin manifestations, however, xerosis may be coexistent in 50–85% of patients and chronic itching can lead to development of skin lesions, including impetigo, crusts, papules, erosions, ulcerations, and prurigo nodularis.[14] The severity may vary over time without related precipitants.[1]

It has been remarkable to note the divergence between the troubling symptoms that patients experience and the under-recognition by nephrology providers. For example, Weisbord et al.[15] studied 75 patients on hemodialysis and 18 physicians. Patients reported a large number of symptoms. In general, physicians had a low rate of awareness of the symptoms and their severity. Pruritus was experienced by 45% of patients with the provider aware of the symptom in only 13% of cases. The authors concluded that 'Renal providers are largely unaware of the presence and severity of symptoms in patients who are on maintenance hemodialysis.'[15] Rayner et al.[4] used DOPPS data to identify symptoms among patients on dialysis. They found that in 2015 that 18% of patients were 'very much or extremely bothered' by itching. Up to 18% received no treatment and 17% did not report itching to health-care staff. Of 268 dialysis medical directors from 17 countries, 69% underestimated pruritus in their centers. Remarkably, in large centers where 21–50% of patients-reported suffering from severe pruritus, 'only 1% of medical directors estimated the same prevalence of pruritus in their facilities'.[4] Data such as these indicate how nephrologists, other providers and dialysis medical directors underestimate suffering from CKD-aP.

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