Differential effects of phosphate binders on vitamin D metabolism in chronic kidney disease

Author:

Ginsberg Charles12,Zelnick Leila R3,Block Geoffrey A4,Chertow Glenn M5,Chonchol Michel6,Hoofnagle Andrew7,Kestenbaum Bryan3,de Boer Ian H38

Affiliation:

1. Division of Nephrology-Hypertension, University of California, San Diego, San Diego, CA, USA

2. Division of Nephrology, Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA

3. Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, WA, USA

4. Nephrology, Reata Pharmaceuticals, Inc., Plano, TX, USA

5. Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA, USA

6. Division of Renal Diseases and Hypertension, University of Anschutz Medical Center, Aurora, CO, USA

7. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA

8. VA Puget Sound Health Care System, Seattle, WA, USA

Abstract

Abstract Background Phosphate binders are commonly used in the treatment of patients with hyperphosphatemia. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism are unknown. Methods We performed a secondary analysis of the Phosphate Normalization Trial in which patients with moderate to advanced chronic kidney disease were randomized to receive either placebo, sevelamer carbonate, lanthanum carbonate or calcium acetate for 9 months. We evaluated changes in serum concentrations of vitamin D metabolites including 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 (VMR)] and the ratio of serum 1,25(OH)2D to 25-hydroxyvitamin D. Results Compared with placebo, randomization to the calcium acetate arm was associated with a 0.6 ng/mL (95% CI 0.2, 1) and 13.5 pg/ng (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 pg/ng (95% CI −20, −3.5) reduction in 24,25(OH)2D3 and VMR, respectively. There was no association of the sevelamer arm with the 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 binders to patients with moderate to severe CKD results in unique changes in vitamin D metabolism.

Funder

National Insitutes of Health

NIH

National Institute of Diabetes and Digestive and Kidney Diseases

NIH Loan Repayment Program

Northwest Kidney Centers

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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