Associations of Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Concentrations With Death and Progression to Maintenance Dialysis in Patients With Advanced Kidney Disease

Background: Low vitamin D concentrations are prevalent in patients with chronic kidney disease (CKD). We investigated the relationship between plasma 25-hydroxyvitamin D (25[OH] D) or 1,25-dihydroxyvitamin D (1,25[OH](2)D) concentrations with death, cardiovascular events, and dialysis therapy initiation in patients with advanced CKD. Study Design: The HOST (Homocysteinemia in Kidney and End Stage Renal Disease) Study was a randomized double-blind trial evaluating the effects of high doses of folic acid on death and long-term dialysis therapy initiation in patients with advanced CKD (stages 4 and 5 not yet on dialysis therapy). 25(OH) D and 1,25(OH)(2)D were measured in stored plasma samples obtained 3 months after trial initiation and evaluated at clinically defined cutoffs (<10, 10-30, and >30 ng/mL) and tertiles (<15, 15-22, and >22 pg/mL), respectively. Cox proportional hazard models were used to examine the association between vitamin D concentrations and clinical outcomes. Setting & Participants: 1,099 patients with advanced CKD from 36 Veteran Affairs Medical Centers. Predictors: 25(OH) D and 1,25(OH)(2)D concentrations. Outcomes: Death, cardiovascular events, and time to initiation of long-term dialysis therapy. Results: After a median follow-up of 2.9 years, 41% (n = 453) died, whereas 56% (n = 615) initiated dialysis therapy. Mean 25(OH) D and 1,25(OH)(2)D concentrations were 21 +/- 10 ng/mL and 20 +/- 11 pg/mL, respectively. After adjustment for potential confounders, the lowest tertile of 1,25(OH)(2)D was associated with death (HR, 1.33; 95% CI, 1.01-1.74) and initiation of long-term dialysis therapy (HR, 1.78; 95% CI, 1.40-2.26) compared with the highest tertile. The association with death and initiation of dialysis therapy was moderately attenuated after adjustment for plasma fibroblast growth factor 23 (FGF-23) concentrations (HRs of lower tertiles of 1.20 [95% CI, 0.91-1.58] and 1.56 [95% CI, 1.23-1.99], respectively, compared with highest tertile). There was no association between 25(OH) D concentrations and outcomes. Limitations: Participants were mostly men. Conclusions: Low plasma 1,25(OH)(2)D concentrations are associated with death and initiation of long-term dialysis therapy in patients with advanced CKD. FGF-23 level may attentuate this relationship. Am J Kidney Dis. 60(4):567-575. (C) 2012 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.