Potentially modifiable factors associated with longitudinal health-related quality of life in the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort

Introduction
People with non-dialysis-dependent chronic kidney disease (NDD-CKD) experience worse health-related quality of life (HRQoL) than those without. This study hypothesised that potentially modifiable factors affecting longitudinal HRQoL in a NDD-CKD cohort could be identified in order to identify potential therapeutic targets for improving HRQoL outcomes.

Methods
The NURTuRE-CKD cohort study recruited 2996 participants with NDD-CKD from UK nephrology centres from 2017. Sociodemographic, medical history, medication, anthropometric, biomarker and patient-reported outcome measure (PROM) data were collected at baseline and first follow-up. HRQoL was measured at second follow-up. The primary outcome was HRQoL measured by EQ-5D-5L, mapped to EQ-5D-3L index value and visual analogue score (VAS). Multivariable mixed effects linear regression models were adjusted and fit to examine the effect of potentially modifiable factors at baseline on longitudinal EQ-5D-3L index value. Similar models were also fit to assess the effects of change in these factors across follow-up on index value and VAS.

Results
2062 participants (68.8%) attended first and 1019 (34.0%) second follow-up. EQ-5D-5L responses worsened over time for index value, VAS and in each dimension. Baseline factors independently associated with worse longitudinal HRQoL were obesity, smoking, sarcopenia, pain, breathlessness, weakness, anxiety, depression and raised parathyroid hormone (PTH), whereas renin-angiotensin-system inhibitor use at baseline was associated with improved HRQoL. The status of factors across follow-up such as persistent obesity, new sarcopenia, increasing phosphate, new and persistent anxiety and depression, and worsening pain were associated with worse HRQoL, whereas improved acidosis, improved pain and weakness were associated with improved HRQoL.

Conclusion
Several potentially modifiable factors independently associated with HRQoL, and NDD-CKD interventions should consider these as therapeutic targets, as well as part of holistic CKD care.