Decreased glomerular filtration rate (GFR) leads to reduced production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 (25(OH)D3). Effects of low GFR on vitamin D catabolism are less well understood. We tested associations of estimated GFR (eGFR) with the circulating concentration of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), the most abundant product of 25(OH)D3 catabolism, across populations with a wide range of GFR.
Setting & Participants
9596 participants in 5 cohort studies and clinical trials: the Diabetes Control and Complications Trial (N=1193), Multi-Ethnic Study of Atherosclerosis (N=6470), Cardiovascular Health Study (N=932), Seattle Kidney Study (N=289), and Hemodialysis Study (N=712).
Circulating 24,25(OH)2D3 concentration.
GFR was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation. Vitamin D metabolites were measured by mass spectrometry.
Circulating 24,25(OH)2D3 concentration was correlated with circulating 25(OH)D3 concentration (Pearson r range, 0.64–0.88). This correlation was weaker with lower eGFR. Moreover, the increment in 24,25(OH)2D3 associated with higher 25(OH)D3 (“slope”) was lower with lower eGFR: 2.06 (95% CI, 2.01–2.10), 1.77 (95% CI, 1.74–1.81), 1.55 (95% CI, 1.48–1.62), 1.17 (95% CI, 1.05–1.29), 0.92 (95% CI, 0.74–1.10), 0.61 (95% CI, 0.22–1.00), and 0.37 (95% CI, 0.35–0.39) ng/mL 24,25(OH)2D3 per 10 ng/mL 25(OH)D3 for eGFR ≥90, 60–89, 45–59, 30–44, 15–29, and <15 mL/min/1.73 m2 and ESRD treated with hemodialysis, respectively. As a result, at a 25(OH)D3 concentration of 20 ng/mL, mean 24,25(OH)2D3 concentration was 2.92 (95% CI, 2.87–2.96), 2.68 (95% CI, 2.64–2.72), 2.35 (95% CI, 2.26–2.45), 1.92 (95% CI, 1.74–2.10), 1.69 (95% CI, 1.43–1.95), 1.14 (95% CI, 0.62–1.66), and 1.04 (95% CI,1.02–1.07) ng/mL for each category, respectively. This interaction was independent of other relevant clinical characteristics. Race, diabetes, urine albumin excretion, and the circulating concentrations of parathyroid hormone and fibroblast growth factor 23 more modestly modified the association of 24,25(OH)2D3 with 25(OH)D3.
Lack of direct pharmacokinetic measurements of vitamin D catabolism.
Lower eGFR is strongly associated with reduced vitamin D catabolism as measured by circulating 24,25(OH)2D3 concentration.