Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3 Supplementation in patients with chronic kidney disease on hemodialysis

Abstract

Background & aims: While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D₂ and Vitamin D₃ is becoming increasingly common in these patients, little is known about 24,25(OH)₂D₃ metabolite production. Some authors report that the CYP24A1 enzyme is upregulated in CKD, but reports of low serum levels of 24,25(OH)₂D₃ in these patients bring this into question. Lack of substrate or increased clearance of the metabolite have been proposed as possible causes. We report serum 24,25(OH)₂D₃ levels from three controlled trials of Vitamin D₂ and Vitamin D₃ supplementation which reached adequate levels of 25(OH)D in patients with end stage renal disease on dialysis.

Methods: 680 samples from three controlled trials of Vitamin D₂ or Vitamin D₃ supplementation in CKD Stage 5D were available for analysis. The trials used single doses of 50,000 IU Vitamin D₃, or 50,000 IU Vitamin D₂, or weekly doses of 10,000 IU or 20,000 IU Vitamin D₃. Blood samples were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D and 24,25(OH)₂D₃ levels were measured using a novel, very sensitive LC-MS/MS-based method involving derivatization with DMEQ-TAD. Linear mixed effect regression models were used to compare the 3 studies and the interventions within studies over time.

Results: The subjects given Vitamin D₃ had significant increases in 25(OH)D levels. Serum 24,25(OH)₂D₃ levels were low at baseline in the renal patients and rose slightly with native vitamin D supplementation, but these levels were lower than reports of 24,25(OH)₂D₃ in healthy populations.

Conclusions: We conclude that the enzymatic activity of CYP24A1 is abnormal in end stage renal patients on dialysis. These trials were registered on clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and NCT01675557 on 8/28/2012.

Keywords: 24,25-Dihydroxyvitamin D(3); Chronic renal disease; Drug metabolism; Hemodialysis; Vitamin D.