From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration, School of Health Administration (G.T.), Anhui Medical University, Hefei, China; Department of Cardiology, First People’s Hospital, Lianyungang, China (D.Y.); and Department of Cardiology (Y.H.) and Department of Pharmacy (Y.C.), Peking University First Hospital, Beijing, China.
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We aimed to test the hypothesis that treatment with enalapril and folic acid is more effective in preventing new-onset proteinuria than enalapril alone among hypertensive patients. This is a post hoc analysis of the renal substudy of the CSPPT (China Stroke Primary Prevention Trial). A total of 13 071 eligible participants without proteinuria were randomized to receive a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n=6511) or 10-mg enalapril alone (n=6560). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. Secondary outcomes included a composite of the primary outcome and all-cause death and the annual rate of estimated glomerular filtration rate decline. After a median 4.4 years of treatment, the primary event occurred in 213 (3.9%) and 188 (3.5%) participants, respectively, in the enalapril and the enalapril–folic acid group (odds ratio, 0.90; 95% confidence interval, 0.74–1.11). However, among participants with diabetes mellitus at baseline, folic acid therapy resulted in a significant reduction in the risk for the primary event (3.7% in the enalapril–folic acid group versus 7.4% in the enalapril group; odds ratio, 0.48; 95% confidence interval, 0.29–0.81) and the composite event (odds ratio, 0.62; 95% confidence interval, 0.42–0.92) and a 55% slower annual rate of estimated glomerular filtration rate decline (0.5% versus 1.1% per year; P=0.002). Among those without diabetes mellitus at baseline, there were no between-group differences in all the outcomes. In conclusion, enalapril–folic acid therapy, compared with enalapril alone, significantly reduced the development of proteinuria in diabetic patients with hypertension.Clinical Trial Registration—URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00794885.