Health-Related Quality of Life in Clinical Trials of CKD Progression

BACKGROUND: Several novel pharmacological therapies for chronic kidney disease (CKD) have been shown to reduce risks of disease progression, cardiovascular events, and mortality. However, their effects on health-related quality of life (HRQoL) remain scattered across trials and are difficult to interpret, owing to variability in instruments used and other design related factors. METHODS: PubMed and Web of Science were searched for randomized clinical trials of pharmacological interventions aimed at slowing CKD progression in adults with non-dialysis CKD, published between January 2000 and January 2026. Two authors independently screened and extracted data. Data on study characteristics, HRQoL instruments used, and intervention effects were synthesized descriptively, and key methodological considerations were reviewed. RESULTS: Of 16,624 screened records, 13 trials collected HRQoL data. HRQoL was measured mainly using the EuroQol 5-Dimension questionnaire (EQ-5D; n=8), the 36-Item Short Form Health Survey (SF-36; n=4), or the Kidney Disease Quality of Life-36 questionnaire (KDQOL-36; n=5). Nine trials reported the effects of interventions on HRQoL. Three demonstrated statistically significant effects in at least one HRQoL domain, all involving interventions that also slowed CKD progression. Effects were generally greater for physical than for mental health domains and were detected more frequently using the disease-specific KDQOL-36, particularly in the symptoms and effects domains, than using the generic EQ-5D. Observed population average intervention effects generally were below conventional minimal clinically important difference thresholds at the population level, though individual-level benefits were evident. CONCLUSIONS: The impact of disease-modifying therapies on HRQoL in non-dialysis CKD is heterogeneous, instrument-dependent, and domain-specific. Consideration of the selected instrument, baseline HRQoL, duration of follow-up, missing data, and potential mediation through clinical events is important when interpreting HRQoL findings. Future trials should incorporate kidney-specific HRQoL instruments and report results for all domains using multiple effect measures.