25-hydroxyvitamin D, Fibroblast Growth Factor 23, and Risk of Acute Kidney Injury Over 20 Years of Follow-Up

Introduction: Low serum 25-hydroxyvitamin D levels have been identified as a risk factor for acute kidney injury (AKI) among critically ill patients. Whether low 25-hydroxyvitamin D levels are associated with long-term incidence of hospitalization with AKI in the general population is unknown. Methods: Among 12,380 participants (mean age, 57 years; 24% black) in the Atherosclerosis Risk in Communities (ARIC) Study who attended visit 2 (1990–1992), we explored the association of serum 25-hydroxyvitamin D with incident hospitalization with AKI. Multivariable Cox models were used to estimate hazard ratios (HRs). We also examined the association of serum fibroblast growth factor 23 (FGF23) with AKI. Results: During a median follow-up of 24.3 years, 2145 participants had incident hospitalization with AKI (crude incidence rate: 8.3; 95% confidence interval [CI]: 8.0–8.7, per 1,000 person-years). In multivariable Cox models (including adjustment for kidney function), lower 25-hydroxyvitamin D and higher FGF23 levels were each significantly associated with an increased risk of AKI (HR: 1.35; 95% CI: 1.17–1.54, for lowest vs. highest quartile for 25-hydroxyvitamin D, and HR: 1.19; 95% CI: 1.05–1.36, for highest vs. lowest quartile for FGF23). The association was consistent across demographic and clinical subgroups, regardless of whether AKI was the primary diagnosis for hospitalization, and when adjusting for incident chronic kidney disease (CKD) or cardiovascular disease (CVD) as a time-varying covariate. Conclusion: Among middle- to older-age adults in the community, low 25-hydroxyvitamin D and high FGF23 levels were independently associated with an increased risk of AKI. Future studies should explore underlying mechanisms linking these bone mineral metabolism markers with kidney injury.