Abstract

Abstract Background and Aims Differences between the sexes are apparent in the epidemiology of CKD. Cross-sectional studies show that women consistently report a poorer health-related quality of life (QoL) than men, however, longitudinal studies are lacking. Here we investigate the sex-specific evolution of QoL over time in advanced CKD. As a secondary aim, we explore the sex-specific determinants of QoL. Method EQUAL is an observational prospective cohort study in stages 4 and 5 CKD patients ≥65 years not on dialysis with an incident estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73m². Data on QoL (measured using the RAND-36), clinical and demographic patient characteristics were collected between April 2012 and September 2020. QoL trajectories were modelled by sex using linear mixed models, and joint models were applied to deal with informative censoring. We followed patients until death or dialysis initiation. Results We included 5151 QoL measurements in 1416 patients over a total of 1986 person years of follow-up. Overall, the physical component summary (PCS) declined with 2.0 (95% CI 1.4-2.6) points and the mental component summary (MCS) by 2.4 (95% CI 1.8-3.0) points per year. Although women had overall lower QoL scores, figure 1 demonstrates that PCS and MCS declined more than twice as fast in men (PCS: 2.4 per year, 95% CI 1.7 – 3.1, MCS: 2.9 per year, 95% CI 2.2 – 3.6) compared with women (PCS: 1.1 per year, 95% CI -0.2 – 2.0, MCS: 1.5 per year, 95% CI 0.5 – 2.4). We identified a non-linear interaction effect between sex and eGFR levels on QoL, demonstrating a stronger negative effect of decreased eGFR on both PCS (p=0.02) and MCS (p=0.04) in men compared with women. Subsequent adjustment for renal decline attenuated the difference in rate of QoL decline between men and women (difference after adjustment; PCS: 1.1, 95% CI -0.1 – 2.2, MCS: 1.2, 95% 0.0 – 2.3). In univariable analyses, higher serum haemoglobin was more beneficial to QoL in men compared to women (p-value for interaction; PCS: p=0.03, MCS: p=0.01). Higher serum phosphate had a strong harmful effect on both PCS and MCS in men, but not in women (PCS & MCS: p<0.001). The presence of pre-existing diabetes had a negative effect on PCS and MCS in men, but to a lesser extent in women (PCS: p=0.02, MCS: p=0.01). Conclusion Despite the higher overall QoL reported by men, both their physical and mental QoL declined approximately twice as fast compared with women. The faster decline in men was mediated in part by their lower levels of renal function, which had a stronger impact on their QoL as compared with women. Furthermore, in exploratory analyses we identified that high levels of phosphate, low levels of haemoglobin, and pre-existing diabetes were more detrimental to QoL in men than in women.

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