Sleep Disturbances in Chronic Kidney Disease – The CKD-REIN Cohort Study

Rationale & Objective Insomnia and excessive daytime sleepiness (EDS) are common in patients with chronic kidney disease (CKD), but their determinants are poorly understood. We analyzed multiple factors likely to affect sleep with the aim of disentangling the contributions of CKD markers and symptoms from those of social factors, lifestyle, comorbidities, and drug-induced effects, the latter two highly prevalent in this population. Study Design Prospective cohort study Setting & Participants 2,765 patients with CKD stages 2-5 not on dialysis (mean age, 67±13 years; 66% men) from a representative sample of 40 nephrology clinics in France. Exposures Albuminuria, estimated glomerular filtration rate (eGFR), CKD symptoms, lifestyle, comorbidities, and medications collected annually. Outcomes Insomnia and EDS ≥ 3 times/week in the past 3 months assessed with a standardized questionnaire at baseline, 1-, 3-, and 5-year follow-ups , providing 7264 observations overall. Analytical Approach Adjusted odds ratios (OR) of insomnia and EDS associated with time-updated exposures estimated with mixed effects logistic regressions. Results Baseline prevalence of reported insomnia was 22% (95% confidence interval, 21-24%) and that of EDS, 15% (14-16%). Based on the 7,264 observations, neither prevalence was associated with albuminuria after adjustment for age and sex. The OR of EDS alone increased significantly with decreasing eGFR, 1.16 (1.05-1.28) per 10 mL/min/1.73m 2 , independent of social factors, physical activity, obesity, heart failure, and long half-life benzodiazepine use. It was no longer significant after adjustment for fatigue, which displayed a strong dose-effect relation with EDS, depression, insomnia, and sleep apnea. Insomnia prevalence increased strongly with severity of cramps, itching, and stress, independent of other determinants including female sex, heart failure, thyroid hormone use, depression, and sleep apnea. Limitations Self-reported sleep disturbances and limited longitudinal inference Conclusions This study highlights the multifactorial nature of sleep disturbances in CKD and the potentially modifiable contribution of CKD symptoms and drug-induced effects.