Endocrine Abstracts

Reduced renal synthesis of 1,25-dihydroxyvitamin D (1,25(OH)₂D) from 25-hydroxyvitamin D (25OHD) in end stage renal disease (ESRD) results in low serum 1,25(OH)₂D. This appears to be due to reduced renal cell function and elevated serum fibroblast growth factor 23 (FGF23). Treatment strategies have therefore focussed on 1,25(OH)₂D or its synthetic analogues, alfacalcidol or paricalcitol. However this overlooks 25-hydroxyvitamin D (25OHD) deficiency, which is common in ESRD. In the current study a subset of 33 haemodialysis patients from Coventry and Warwickshire were assessed during routine supplementation with vitamin D₃ to raise serum 25OHD (colecalciferol supplementation: serum 25OHD <50 nmol/L repletion dose of 40,000IU for 3 months, ≥50 nmol/L maintenance dose of 20,000IU fortnightly, >150 nmol/L stop and recheck in 3 months). Multiple serum vitamin D metabolites were measured using liquid chromatography-tandem mass spectrometry at baseline (T0) and after 12 months supplementation (T12). Serum 25OHD increased significantly from 37.4±4.38 nmol/L at T0 to 117.7±6.61 nmol/L at T12 (P<0.001) with 88% of patients ≥75 nmol/L. Serum 1,25(OH)₂D also increased significantly in 94% of patients (P<0.001) from 43.4±4.75 pmol/L to 91.2±5.30pmol/L at T12. Parallel analyses showed that serum calcium increased following colecalciferol supplementation (T0 vs. T12, 2.35±0.03 to 2.45±0.03 mmol/L, P<0.05), no hypercalcaemia was associated with colecalciferol supplementation. At T0 levels of 1,25(OH)₂D and 24,25(OH)₂D correlated with 25OHD (P<0.05). However, once 25OHD was replete (T12) this correlation was lost. Serum calcium correlated with 1,25(OH)₂D at T12, but not at T0. These data suggest serum 25OHD was limiting at T0. This study indicates that vitamin D repletion in haemodialysis patients is safe and significantly increases serum 1,25(OH)₂D. Demonstrating that kidneys with a low GFR and elevated FGF23 retain the ability to synthesise 1,25(OH)₂D in a substrate-dependent fashion. Complementing 1,25(OH)₂D analogue treatment with colecalciferol may prove effective in managing bone and mineral disorders associated with renal disease.