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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.

Author(s): Kendrick J, Cheung AK, Kaufman JS, Greene T, Roberts WL, Smits G, Chonchol M; HOST (Homocysteinemia in Kidney and End Stage Renal Disease) Study Investigators.

Collaborators: Young E, Belanger K, Lopez R, Grunsten N, Sanders P, Killian D, Shanklin N, Kaufman J, Dibbs E, Langhoff E, Tyrrell D, Crowley S, Peixoto A, DeLorenzo A, Joncas C, Miller RT, Kaelin K, Markulin M, Dev D, Coussirat D, Sajgure A, Saklayen M, Neff H, Shook S, Chonchol M, Levi M, Clegg L, Singleton A, Abu-Hamdan D, Bey-Knight L, King K, Jones E, Palant C, Sheriff H, Simmons C, Sinks J, Wingo C, McAllister B, Sallustio J, Smith N, Popli S, Linnerud P, Zuluaga A, Dolson G, Tasby G, Agarwal R, Lewis R, Jasinski D, Sachs N, Veneck D, Rehman S, Basu A, Ingram K, Paul R, Raymond J, Holmes K, Wiegmann T, Abdallah J, Nagaria A, Smith D, Renft A, Finnigan T, Feldman G, Schmid S, Cooke C, Wall B, Patterson R, Contreras G, Jaimes E, O'Brien G, Ma K, Rust J, Otterness S, Batuman V, Kulivan C, Goldfarb DS, Shea M, Modersitzki F, Dixon T, Pastoriza E, Titus L, Jamison R, Cook I, Anderson M, Palevsky P, Salai P, Anderson S, Walczyk J, Lindner A, Stehman-Breen C, Pascual E, Nugent-Carney J, Thomson S, Mullaney S, Dingsdale J, Rosado C, Azcona-Vilchez C, Betcher S, Rewakowski C, Cohen D, Flanagin G, Steffe J, Lohr J, Fucile N, Yohe L, Blumenthal S, Schmidt D.

Affiliation(s): Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, USA.

Publication date & source: 2012, Am J Kidney Dis. , 60(4):567-75

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.

Page last updated: 2013-02-10

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