Folic Acid Attenuates Contrast-Induced Nephropathy in Patients With Hyperhomocysteinemia Undergoing Coronary Catheterization: A Randomized Controlled Trial

Long Peng, Xing Shui, Fang Tan, Zexiong Li, Yesheng Ling, Bingyuan Wu, Lin Chen, Suhua Li, Hui Peng, Long Peng, Xing Shui, Fang Tan, Zexiong Li, Yesheng Ling, Bingyuan Wu, Lin Chen, Suhua Li, Hui Peng

Abstract

Background: Hyperhomocysteinemia is a risk factor for contrast-induced nephropathy. Folic acid can attenuate such nephropathies in rats. The protective effect of folic acid against contrast-induced nephropathy has not been studied in humans. We aimed to investigate the effect of folic acid on the incidence of contrast-induced nephropathy (CIN) after coronary catheterization in patients with hyperhomocysteinemia. Methods: This was a single-center, prospective, double-blind, randomized controlled trial (ClinicalTrials.gov, NCT02444013). In total, 412 patients (mean age: 65 ± 12 years, 268 male) with plasma homocysteine ≥15 μM, who underwent coronary arteriography (CAG) or percutaneous coronary intervention (PCI) from May 2015 to August 2018, were enrolled. Patients were randomly assigned to two groups: a treatment group (n = 203), taking 5 mg of folic acid (orally, three times/day) immediately after enrollment and for 72 h after operation, and a control group (n = 209), taking placebo. Contrast-induced nephropathy was defined as an increase in serum creatinine of >25% or 44 μM within 48 or 72 h after contrast medium administration. Results: In total, 50 (12%) patients developed CIN after 48 h after catheterization, including 16 (8%) in the treatment group and 34 (16%) in the control group (P = 0.009). Meanwhile, 53 (13%) patients developed CIN after 72 h of CAG/PCI, including 18 (9%) in the treatment group and 35 (17%) in the control group (P = 0.017). The incidence of contrast-induced nephropathy in the treatment group was lower than that in the control group (P = 0.017). Logistic regression analysis confirmed that administration of folic acid was a protective factor against contrast-induced nephropathy (RD = 0.0788, 95%CI: 0.0105-0.1469, P = 0.019). We found no serious adverse events associated with folic acid. No death or hemodialysis occurred in either group. Conclusions: Perioperative administration of folic acid attenuates the incidence of contrast-induced nephropathy after coronary catheterization in patients with hyperhomocysteinemia. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT02444013].

Keywords: acute kidney injury; contrast-induced nephropathy; coronary catheterization; folic acid; hyperhomocysteinemia.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Peng, Shui, Tan, Li, Ling, Wu, Chen, Li and Peng.

Figures

Figure 1
Figure 1
Flowchart of the study population of patients with hyperhomocysteinemia receiving folic acid and the control group. CAG, coronary arteriography; PCI, percutaneous coronary intervention; eGFR, estimated glomerular filtration rate.
Figure 2
Figure 2
Homocysteine (Hcy) change over time in patients with hyperhomocysteinemia receiving folic acid and the control group. One-way ANOVA was used to analyze intergroup differences with a Bonferroni multiple comparison post-test. P < 0.0167 were considered statistically significant. The linear mixed model showed significant differences in the change in Hcy concentration between the two groups due to the interaction between the groups and time (P < 0.001). The folic acid group showed a faster decline. The average of the control group was 0.81 lower than that of the folic acid group at baseline, 6.02 higher than that of the folic acid group before procedure, and 9.05 higher than that at 72 h after procedure. ANOVA, analysis of variance; CAG, coronary arteriography; PCI, percutaneous coronary intervention.

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