The relationship between chronic kidney disease–associated pruritus and health-related quality of life: a systematic review

Abstract

Background Chronic kidney disease associated pruritus (CKD-aP) is a common and burdensome condition for end-stage kidney disease (ESKD) patients, especially those receiving haemodialysis. High quality evidence of the relationship between CKD-aP and health-related quality of life (HRQoL) can therefore inform clinicians and policy makers about treatment choice and reimbursement decisions. Methods Systematic Literature Review and narrative synthesis, stratified by study design and HRQoL instrument was conducted to evaluate the relationship in Adult ESKD patients receiving in-centre haemodialysis between CKD-aP, and HRQoL, assessed using a multi-dimensional, generic or condition-specific, preference- or non-preference-based measures. MEDLINE, EMBASE, Web of Science and BIOSIS Citation indexes, Cochrane Library and PsycINFO from inception to March 2020 were searched with two reviewers extracting data independently. Results Searches identified 2,684 unique records, of which 20 papers relating to 18 unique studies (5 randomised controlled trials and 13 observational studies) were included. HRQoL was assessed using 4 generic and 8 disease-specific measures. The impact of CKD-aP was assessed by comparison of means, linear regression and correlation. Observational studies employing comprehensively adjusted multivariable linear regression largely found associations between CKD-aP severities and HRQoL. Analyses suggest this relationship is partially mediated by the sleep disturbance caused by CKD-aP. RCTs showing improvements in CKD-aP severity were associated with clinically meaningful improvements in HRQoL. Compared to generic measures, disease-specific HRQoL instruments reported greater changes with reduced CKD-aP. Heterogeneity in study design and reporting precluded meta-analysis. Conclusions CKD-aP severity was found to be associated with a worsening of HRQoL in the majority of observational and RCT studies. Parallel improvements in CKD-aP and HRQoL with interventions may support their use. (PROSPERO Registration Number 175035)

Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial

“…Patients and healthcare professionals have prioritised other measures of HRQoL in people on dialysis [ 32 ], and other randomised controlled trials (RCTs) have shown the relative insensitivity of the EQ-5D instrument in this patient group [ 33 ]. A recent systematic review of the impact of CKD-aP on HRQoL reported that RCTs that showed improvements in CKD-aP severity were associated with clinically meaningful improvements in HRQoL [ 34 ]. It was also noted that disease-specific HRQoL instruments reported greater changes with reduced CKD-aP severity than generic instruments [ 34 ], and this has been shown in other skin conditions [ 35 ].…”

“…A recent systematic review of the impact of CKD-aP on HRQoL reported that RCTs that showed improvements in CKD-aP severity were associated with clinically meaningful improvements in HRQoL [ 34 ]. It was also noted that disease-specific HRQoL instruments reported greater changes with reduced CKD-aP severity than generic instruments [ 34 ], and this has been shown in other skin conditions [ 35 ]. This recognised lack of sensitivity led to the development of the disease-specific ‘bolt-on’ module – EQ-PSO [ 24 ]; this added ‘skin irritation’ and ‘self-confidence’, which were observed to improve in this study.…”

Relationship Between Standardized Measures of Chronic Kidney Disease-associated Pruritus Intensity and Health-related Quality of Life Measured with the EQ-5D Questionnaire: A Mapping Study

“…Systematic reviews and these trials have shown that disease-specific HRQoL measures are sensitive to changes in pruritus severity in CKD-aP, but the degree to which EQ-5D improves with lessening CKD-aP severity within individuals remains unobserved ( 5 ): open-label trial data for the use of difelikefalin for CKD-aP that also included EQ-5D-5L is available for comparison ( 31 ): participants being treated with difelikefalin had a clinically meaningful change in EQ-5D utility of 0.04, and 73.7% of patients on difelikefalin improved their WI-NRS by ≥3 points (comparable to 1 Verbal Rating Scale level). Due to the nature of the trial’s reported data and the cross-sectional study design twe are unable to confirm if changes in CKD-aP severity in response to therapies yield similar improvements in HRQoL as those estimated from our analyses.…”

“…of the pruritus is associated with depression, poor sleep quality, increased mortality and reduced health-related quality of life (HRQoL) (3)(4)(5). Patients and clinicians have repeatedly prioritized the treatment of CKD-aP (6).…”

“…There is increasing recognition that urea, other uraemic toxins and phosphate do not have a mechanistic role in the development of pruritus in this patient group, leading to the revised term CKD-aP. Existing evidence suggests that the severity of the pruritus is associated with depression, poor sleep quality, increased mortality and reduced health-related quality of life (HRQoL) ( 3 – 5 ). Patients and clinicians have repeatedly prioritized the treatment of CKD-aP ( 6 ).…”