Risk of incident chronic kidney disease is better reduced by bedtime than upon-awakening ingestion of hypertension medications.

Abstract

This trial investigated whether therapy with the entire daily dose of ≥1 hypertension medications at bedtime exerts a greater reduction in the risk of incident chronic kidney disease (CKD) than therapy with all medications upon awakening. We conducted a prospective, open-label, blinded endpoint trial of 2078 hypertensive patients without CKD (1017 men/1061 women, 53.6 ± 13.7 years of age) randomized to ingest all their prescribed hypertension medications upon awakening (n = 1041) or the entire daily dose of ≥1 of those medications at bedtime (n = 1037). During a 5.9-year median follow-up, 368 participants developed CKD. Patients of the bedtime, compared with the morning, treatment group showed (i) significantly lower asleep blood pressure (BP) mean, greater sleep-time relative BP decline, and attenuated prevalence of non-dipping at the final evaluation (38 vs. 55%; P < 0.001); and (ii) a significantly lower hazard ratio of CKD, adjusted for the significant influential characteristics of age, serum creatinine, urinary albumin, type 2 diabetes, previous cardiovascular event, asleep systolic BP mean, and sleep-time relative systolic BP decline (0.27 (95% confidence interval: 0.21-0.36); event-rate 8.3 vs. 27.1% in the bedtime and morning-treatment groups; P < 0.001). Greater benefit was observed for bedtime than awakening treatment, with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In hypertensive patients without CKD, ingestion of ≥1 BP-lowering medications at bedtime, mainly those modulating or blocking the effects of angiotensin II, compared with ingestion of all such medications upon-awakening, resulted in improved ambulatory BP control (significant further decrease of asleep BP and enhanced sleep-time relative BP decline) and reduced risk of incident CKD.