Abstract—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.

Detail Information
Li Y, Liang M, Wang G, Wang B, He M, Tang G, Yin D, Xu X, Huo Y, Cui Y, Hou FF, Qin X.Effects of Folic Acid Therapy on the New-Onset Proteinuria in Chinese Hypertensive Patients: A Post Hoc Analysis of the Renal Substudy of CSPPT (China Stroke Primary Prevention Trial).Hypertension. 2017 Aug;70(2):300-306. Epub 2017 Jun 12.