Evidence for persistent vitamin D 1-alpha-hydroxylation in hemodialysis patients: Evolution of serum 1,25-dihydroxycholecalciferol after 6 months of 25-hydroxycholecalciferol treatment

Background: End-stage renal disease (ESRD) patients are thought to have impaired 1-alpha-hydroxylase capacity, but an extrarenal source of 1,25(OH)(2) D has been recognized. Objective: The aim of this study was to assess the evolution of serum 1,25(OH)(2) D in hemodialysis (HD) patients with vitamin D deficiency after 6 months of 25(OH)(3) supplementation, and to identify the factors associated with persistent 1,25(OH)(2) D production. Methods: HD patients in a HD center with vitamin D deficiency (i.e. 25(OH) D < 75 nmol/l) who were not receiving any vitamin D derivatives or calcimimetics were studied. Patients who had previously undergone parathyroidectomy or nephrectomy or those with uncontrolled hypercalcemia or hyperphosphatemia were excluded from this study. The patients were administrated a dose of 10-30 mu g/day of oral 25(OH)D-3 based on the severity of their deficiency. The serum levels of 25(OH)D and 1,25(OH)(2) D evolution after 6 months were recorded. Responders were defined as patients with an increase in serum 1,25(OH)(2) D levels greater than the median value. Changes in mineral metabolism parameters were compared with those in the nonresponders. Results: Of the 253 patients, 225 (89%) were vitamin D-deficient, and 43 met the inclusion criteria. The patients were 72.6 +/- 8 10 years old and had been on dialysis for 71 +/- 70 months; 39% of the patients were female and 45% were diabetics. From baseline to 6 months of treatment, serum 25(OH)D levels increased from 27.8 +/- 18 to 118 +/- 34 nmol/l (p < 0.001) and serum 1,25(OH)(2)D levels increased from 7.7 +/- 5 to 30.5 +/- 15 pmol/l (p < 0.001) with a median increase of 20 pmol/l. The mean serum calcium level increased from 2.19 +/- 0.1 to 2.25 +/- 0.1 mmol/l (p = 0.009), the intact parathyroid hormone (iPTH) level decreased from 144 +/- 108 to 108 +/- 63 pg/ml (p = 0.05), and the bone alkaline phosphatase (BALP) level remained unchanged. The serum phosphate level increased slightly from 1.22 +/- 0.3 to 1.34 +/- 0.2 mmol/l (p = 0.04) with reduced hypophosphatemia. Compared with the responders (n = 24), most of the nonresponders (n = 19) were diabetic (63 vs. 29%, p = 0.02) and had a lesser increase of their 25(OH)D serum level. The serum level of FGF-23 was not significant. A positive correlation was observed between serum 1,25(OH)(2) D and serum 25(OH)D levels after 6 months of 25(OH)D-3 treatment (p = 0.02). Conclusion: The Kidney Disease Outcomes Quality Improvement (KDOQI) guidelines do not recommend checking and treating vitamin D deficiency in chronic kidney disease (CKD) stage 5 patients due to the supposed lack of 1,25(OH)(2) D production. These data confirm persistent renal or extra-renal production of 1,25(OH)(2) D in HD patients after 6 months of 25(OH)D-3 administration. Diabetes is the main factor associated with impaired 1,25(OH)(2) D production. 25(OH)D-3 administration corrects vitamin D deficiency with few effects on mineral metabolism and stability of bone turnover markers. Copyright (C) 2008 S. Karger AG, Basel.