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Abstract: FR-PO169

Differential Effects of Phosphate Binders on Vitamin D Metabolism in CKD

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Ginsberg, Charles, UCSD, San Diego, California, United States
  • Zelnick, Leila R., Kidney Research Institute, Seattle, Washington, United States
  • Block, Geoffrey A., Reata, Denver, Colorado, United States
  • Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
  • Chonchol, Michel, University of Colorado , Aurora, Colorado, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • de Boer, Ian H., Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, United States
Background

Phosphate binders are commonly used in the treatment of patients with advanced chronic kidney disease (CKD) and end stage renal disease. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism is unknown.

Methods

We performed a secondary analysis of the phosphate normalization trial, in which 148 patients with moderate to severe CKD were treated with either sevelamer carbonate, lanthanum carbonate, calcium acetate or placebo. We used linear mixed models to evaluate the relationship between treatment arm and changes in 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the ratio of 24,25(OH)2D3, to 25-hydroxyvitamin D (the vitamin D metabolite ratio or VMR) and the ratio of 1,25(OH)2D to 25-hydroxyvitamin D.

Results

Compared to placebo, randomization to the calcium acetate arm was associated with a 0.6 ng/ml (95%CI 0.2,1) and 13.5 ng/µg (95%CI 5.5,21.5) increase in 24,25(OH)2D and VMR, respectively, and a 5.2 pg/ml (95% CI 1.1,9.4) reduction in 1,25(OH)2D. Randomization to sevelamer carbonate was associated with a 0.5 ng/ml (95% CI -0.9,-0.1) and 11.8 ng/µg (95% CI -20,-3.5) reduction in 24,25(OH)2D3 and VMR respectively. There was no association of sevelamer arm with change in 1,25(OH)2D3, and randomization to lanthanum carbonate was not associated with a change in any of the vitamin D metabolites.

Conclusion

Administration of different phosphate binder classes to patients with moderate-severe CKD results in unique changes in vitamin D metabolism. These findings may have important clinical implications in the management of hyperphosphatemia and vitamin D deficiency.

Adjusted differences in vitamin D metabolite concentrations, by treatment group
 Difference in time trend (95% CI)
Treatment group1,25(OH)D3 (pg/mL)24,25(OH)D3 (ng/mL)1,25(OH)D3:25(OH)D3 (pg/ng)24,25(OH)D3:25(OH)D3 (ng/µg)
PlaceboRefRefRefRef
Lanthanum4 (-0.3, 8.2)-0.3 (-0.7, 0.1)0.13 (-0.03, 0.3)-0.3 (-8.5, 7.9)
Sevelamer0.3 (-3.9, 4.6)-0.5 (-0.9, -0.1)0.12 (-0.05, 0.28)-11.8 (-20, -3.5)
Calcium-5.2 (-9.4, -1.1)0.6 (0.2, 1)-0.21 (-0.37, -0.05)13.5 (5.5, 21.5)
p-value0.003<0.001<0.001<0.001

Entries are modeled differences in time trends (between time t ≥ 3 and baseline), comparing treatment group to placebo, adjusted for age, sex, race, and weight.

Funding

  • NIDDK Support