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

BACKGROUND & AIMS: While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D and Vitamin D is becoming increasingly common in these patients, little is known about 24,25(OH)D metabolite production. Some authors report that the CYP24A1 enzyme is upregulated in CKD, but reports of low serum levels of 24,25(OH)D 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)D levels from three controlled trials of Vitamin D and Vitamin D 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 D or Vitamin D supplementation in CKD Stage 5D were available for analysis. The trials used single doses of 50,000 IU Vitamin D, or 50,000 IU Vitamin D, or weekly doses of 10,000 IU or 20,000 IU Vitamin D. Blood samples were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D and 24,25(OH)D 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 D had significant increases in 25(OH)D levels. Serum 24,25(OH)D 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)D 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.