CKD Progression Delay Observed With Folic Acid Therapy

Enalapril plus folic acid treatment was associated with a 56% reduction in the odds of CKD progression compared with enalapril alone.
Enalapril plus folic acid treatment was associated with a 56% reduction in the odds of CKD progression compared with enalapril alone.

Folic acid treatment may delay progression of chronic kidney disease (CKD) among patients with mild to moderate CKD, according to investigators.

“Our study is the first to show significant renal protection from folic acid therapy in a population without folic acid fortification,” a team led by Fan Fan Hou, MD, PhD, of Southern Medical University in Guangzhou, China, reported online ahead of print in JAMA Internal Medicine.

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In the Renal Substudy of the China Stroke Primary Prevention Trial, hypertensive patients treated with a combination of enalapril and folic acid had a 21% decrease in the odds of CKD progression—the primary outcome—compared with those who received enalapril alone. They also had a significantly slower rate of decline in estimated glomerular filtration rate (eGFR): 1.28% vs 1.42% per year. Among individuals with CKD at baseline, folic acid therapy was associated with a significant 56% reduction in the odds of CKD progression, a significant 33% reduction in the odds of a rapid decline in renal function (defined as an average decline in eGFR of 5 mL/min/1.73 m2 or more per year), and a significant 44% slower decline in renal function (0.96% vs 1.72% per year). Dr Hou and colleagues observed no significant between-group differences among participants without CKD at baseline.

“Given the magnitude of renal protection suggested by this study as well as the safety and the low cost, the potential role of folic acid therapy in the clinical management of patients with CKD in regions without folic acid fortification should be vigorously examined,” Dr Hou's team concluded.

The study included 15,104 hypertensive without a history of major cardiovascular disease who were randomly assigned to daily treatment with either 10 mg enalapril plus 0.8 mg folic acid (7545 participants) or 10 mg enalapril alone (7559 participants). The study population had a median follow-up of 4.5 years. Of the 15,104 participants, 1671 had CKD at baseline and 13,433 did not. The researchers defined CKD as an eGFR less than 60 mL/min/1.73 m2 and/or proteinuria at baseline.

Dr Hou and colleagues defined CKD progression as a decrease in eGFR of 30% or more and to a level below 60 mL/min/1.73 m2 if the baseline eGFR was 60 mL/min/1.73 m2, or a decrease in eGFR of 50% of more if the baseline eGFR was less than 60 mL/min/1.73 m2; or the development of end-stage renal disease.

In an editorial accompanying the new report, Patrick J. Stover, PhD, of the Division of Nutritional Sciences at Cornell University in Ithaca, New York, and colleagues noted that the study showed that enalapril interacts with folate in human physiology. They pointed out that enalapril treatment alone in the absence of supplemental folic acid increased serum folate by 5.1 ng/mL. “While the mechanisms for this interaction are unknown and should be explored, this drug-nutrient interaction may underlie the secondary prevention of renal function decline observed in this study,” they wrote.

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