Efficacy of Folic Acid Therapy on the Progression of Chronic Kidney Disease The Renal Substudy of the China Stroke Primary Prevention Trial

IMPORTANCE The efficacy of folic acid therapy on renal outcomes has not been previously investigated in populations without folic acid fortification. OBJECTIVE To test whether treatment with enalapril and folic acid is more effective in slowing renal function decline than enalapril alone across a spectrum of renal function at baseline from normal to moderate chronic kidney disease (CKD) among Chinese adults with hypertension. DESIGN, SETTING, AND PARTICIPANTS In this substudy of eligible China Stroke Primary Prevention Trial (CSPPT), 15 104 participants with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73m(2) or greater, including 1671 patients with CKD, were recruited from 20 communities in Jiangsu province in China. INTERVENTIONS Participants were randomized to receive a single tablet daily containing 10mg enalapril and 0.8mg folic acid (n = 7545) or 10mg enalapril alone (n = 7559). MAIN OUTCOMES AND MEASURES The primary outcomewas the progression of CKD, defined as a decrease in eGFR of 30% or more and to a level of less than 60 mL/min/1.73m(2) if the baseline eGFR was 60 mL/min/1.73m(2) or more, or a decrease in eGFR of 50% or more if the baseline eGFR was less than 60 mL/min/1.73m(2); or end-stage renal disease. Secondary outcomes included a composite of the primary outcome and all-cause death, rapid decline in renal function, and rate of eGFR decline. RESULTS Overall, 15 104 Chinese adults with a mean (range) age of 60 (45-75) years were recruited; median follow-up was 4.4 years. There were 164 and 132 primary events in the enalapril group and the enalapril-folic acid group, respectively. Compared with the enalapril group, the enalapril-folic acid group had a 21% reduction in the odds of the primary event (odds ratio [OR], 0.79; 95% CI, 0.62-1.00) and a slower rate of eGFR decline (1.28% vs 1.42% per year; P =.02). Among the participants with CKD at baseline, folic acid therapy resulted in a significant reduction in the risks for the primary event (OR, 0.44; 95% CI, 0.26-0.75), rapid decline in renal function (OR, 0.67; 95% CI, 0.47-0.96) and the composite event (OR, 0.62; 95% CI, 0.43-0.90), and a 44% slower decline in renal function (0.96% vs 1.72% per year, P <.001). Among those without CKD at baseline, there was no between-group difference in the primary end point. CONCLUSIONS AND RELEVANCE Enalapril-folic acid therapy, compared with enalapril alone, can significantly delay the progression of CKD among patients with mild-to-moderate CKD.