Folate intake and incident chronic kidney disease: a 30-year follow-up study from young adulthood to midlife

Abstract

The relation of long-term dietary folate intake with incident chronic kidney disease (CKD) remains uncertain. We aimed to investigate the association between dietary folate intake and incident CKD in a 30-y follow-up study from young adulthood to midlife. A total of 4038 American adults aged 18-30 y and without reduced estimated glomerular filtration rate (eGFR) were enrolled in 1985-1986 and monitored until 2015-2016 in the CARDIA (Coronary Artery Risk Development in Young Adults) study. Diet was assessed by a validated dietary history questionnaire at baseline, in 1992-1993, and in 2005-2006. The primary outcome was incident CKD, defined as an eGFR <60 mL · min-1 · 1.73 m-2 or a urinary albumin to creatinine ratio (ACR) ≥30 mg/g. The secondary outcomes included 1) incident decreased eGFR, defined as an eGFR <60 mL · min-1 · 1.73 m-2, and 2) incident albuminuria, defined as an ACR ≥30 mg/g. During the follow-up, 642 (15.9%) participants developed CKD. Overall, there was a significant L-shaped relation of dietary folate with incident CKD after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted HRs (95% CIs) in quintiles 2-5 for incident CKD were 0.69 (0.56, 0.85), 0.35 (0.27, 0.45), 0.34 (0.26, 0.45), and 0.39 (0.30, 0.51), respectively. Similar results were found for the secondary outcomes. Moreover, the L-shaped association was confirmed in a subset of the cohort (n = 1462) with serum folate measured at baseline, in 1992, and in 2000. Higher folate intake in young adulthood was longitudinally associated with a lower incidence of CKD later in life. Additional studies are warranted to establish the causal inference.