Folic Acid Slows Progression of Kidney Disease

By Will Boggs MD

NEW YORK - Addition of folic acid to enalapril slows the progression of chronic kidney disease (CKD), researchers from China report.

"Given the magnitude of the renal protection indicated by this trial as well as the safety and low cost of the therapy, we suggest folic acid should be considered in the clinical management of CKD in regions without folic acid fortification," Dr. Fan Fan Hou from Nanfang Hospital, Southern Medical University, Guangzhou, China told Reuters Health by email.

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Hyperhomocysteinemia is prevalent in CKD and may be a risk factor for its progression, but interventional studies using high doses of folic acid and B vitamins in combination have shown no benefit on renal outcomes.

Dr. Hou and colleagues used data from the prespecified renal substudy of the China Stroke Primary Prevention Trial (CSPPT) to examine the effects of the combination of enalapril and folic acid versus enalapril alone in reducing the risk of renal function decline in 15,104 patients with hypertension, including 1,671 (11.1%) with CKD at baseline.

As expected, after a median 4.4 years of follow-up, serum folate levels increased to a greater extent in the enalapril-folic acid group (by 15.4 ng/mL) than in the enalapril-only group (by 5.1 ng/mL), resulting in a significantly greater drop in serum homocysteine in the enalapril-folic acid group (by 1.9 versus 0.2 umol/liter).

The greatest decline in serum homocysteine occurred in the TT homozygotes of MTHFR C677T polymorphism, according to the August 22nd JAMA Internal Medicine online report.

Progression of CKD was 21% less common and estimated GFR declined more slowly (1.28% versus 1.42% per year) with enalapril-folic acid than with enalapril alone.

Among individuals with CKD at baseline, those taking enalapril and folic acid had a 56% lower risk of progression, 33% lower risk of rapid decline in renal function, and a 44% slower rate of renal function decline, compared with those taking enalapril alone.

In exploratory analyses, the risk of CKD progression declined to a greater extent with the addition of folic acid among patients whose baseline estimated GFR was less than 60 mL/min/1.73m2.

"The renal protective effect in those without CKD was nominal," Dr. Hou said. "Confirmation of our findings in an independent population is warranted."

Dr. Patrick J. Stover from Cornell University, Ithaca, New York, who coauthored a related invited commentary, told Reuters Health by email, "Clearly, the most important finding was that the efficacy of enalapril (a pharmaceutical used in the treatment of hypertension and diabetic nephropathy) in slowing renal function decline among Chinese adults with mild to moderate hypertension, was enhanced when co-administered with 0.8 mg of folic acid."

"These results should be confirmed in additional populations, with attention to the optimal dose and form of folate that maximizes the efficacy of enalapril," he said.

Dr. Stover added, "Disease and its treatment can alter the nutritional needs of the patient and the efficacy of pharmaceutical regimens. This study demonstrates that more attention should be given to understanding human nutrition needs in chronic disease."

Dr. Sagar U. Nigwekar from Massachusetts General Hospital and Harvard Medical School in Boston, who recently reviewed interventions for lowering plasma homocysteine levels in dialysis patients, told Reuters Health, "These are highly exciting results considering limited interventions available to delay the progression of chronic kidney disease. What is really striking is that even relatively moderate increases in serum folate level of 15 ng/mL using a low-dose folate supplementation was associated with a remarkable 21% reduction in chronic kidney disease progression on average and >50% reduction in patients with pre-existing chronic kidney disease."

"These results contradict many prior studies on this topic and highlight in which population this intervention is likely to be effective (e.g., where food fortification is not routinely done) and at what dose," he said.

"As exciting as the results are, the study has limitations regarding its generalizability especially to patient populations in countries where folate food fortification is prevalent and when patients even without folate supplementation have levels close to what were achieved with folate supplementation in this trial," Dr. Nigwekar said. "However, if these findings are independently validated in another similar population then will be highly relevant to populations in countries where food fortification is not routinely done and potentially also for patients with low folate levels in countries where fortification is a routine."

"Although in recent years, the sun has set on multiple vitamins (vitamin D, vitamin E), this vitamin trial is highly encouraging for patients with and at risk for chronic kidney disease," he concluded.

SOURCE: https://bit.ly/2bMvOEW

JAMA Intern Med 2016.

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