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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-α-hydroxylase capacity, but an extrarenal source of 1,25(OH)2D has been recognized. Objective: The aim of this study was to assess the evolution of serum 1,25(OH)2D in hemodialysis (HD) patients with vitamin D deficiency after 6 months of 25(OH)D3 supplementation, and to identify the factors associated with persistent 1,25(OH)2D 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 µg/day of oral 25(OH)D3 based on the severity of their deficiency. The serum levels of 25(OH)D and 1,25(OH)2D evolution after 6 months were recorded. Responders were defined as patients with an increase in serum 1,25(OH)2D 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 ± 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)2D 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)2D and serum 25(OH)D levels after 6 months of 25(OH)D3 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)2D production. These data confirm persistent renal or extra-renal production of 1,25(OH)2D in HD patients after 6 months of 25(OH)D3 administration. Diabetes is the main factor associated with impaired 1,25(OH)2D production. 25(OH)D3 administration corrects vitamin D deficiency with few effects on mineral metabolism and stability of bone turnover markers.