Effect of chronotherapy of antihypertensives in chronic kidney disease: A randomized control trial

Introduction: There is a higher prevalence of non-dipping pattern in hypertensive chronic kidney disease (CKD) patients. Nocturnal hypertension has been shown to predict cardiovascular mortality and morbidity and is often superior to daytime blood pressure. We studied the effect of shifting or adding antihypertensive to night time on blood pressure profile of CKD III-IV patients. Methods: In this single-center, prospective, randomized controlled trial, eligible participants were adults from eastern India aged 18–65 years with CKD stages 3 and 4, with a non-dipping pattern on ambulatory blood pressure monitor (ABPM). The intervention group received all the antihypertensives in the night time whereas the standard care group continued to take the medication in the morning. Both groups were followed up for 1 year. The primary outcome was the number of patients changed from non-dippers to dippers in the standard care group and intervention group. Secondary outcomes included a change in estimated glomerular filtration rate (eGFR) and change in the cardiac structure. Results: 39 patients in the intervention group and 36 patients in the standard care group were analyzed. 10 patients (26%) reverted to dipping pattern in the intervention group as compared to none in the standard care group. Mean changes in eGFR were −2.55 and −0.18 mL/min/1.73 m2 in the standard care and intervention group at the end of the study, respectively. Between-group difference in eGFR was significant at 1 year (5.22 [95% CI, 4.3–6.1] ml/min/1.73 m2); (P = 0.03). The cardiac structure showed no significant changes in either group. Conclusions: Bedtime administration of antihypertensives reverted non-dippers to dippers and slowed the decline in eGFR in CKD stages 3 and 4 compared to morning administration of antihypertensives.