#2283 Vitamin D metabolism in end stage kidney failure: people receiving haemodialysis can still synthesise 1,25-dihydroxyvitamin D

Abstract

Abstract Background and Aims A large proportion of haemodialysed patients remain vitamin D deficient, contributing to the development, and severity, of chronic kidney disease-mineral bone disorder (CKD-MBD). This study aimed to investigate the effect of vitamin D (cholecalciferol) supplementation on serum levels of 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in a group of people receiving haemodialysis. Method Eighty-one haemodialysis patients (dialysis vintage ≥1 month) with low serum total 25(OH)D consented to participate. 40,000IU cholecalciferol was given weekly for 12-weeks followed by a maintenance dose of 20,000IU fortnightly (administered by dialysis nursing staff as part of routine care). Patients remained on active vitamin D (1,25(OH)2D3 and analogues) as part of routine care (clinician prescribed for management of calcium and PTH). Baseline and 12-month data were compared using related-samples Wilcoxon signed rank test (Table 1). NHS research ethics committee approval was received. Results Complete data were available and analysed for 55 patients. 1,25(OH)2D3 levels were low at baseline (48.3pmol/L, IQR 35.9-57.9pmol/L) despite 44 of 55 patients (80%) being prescribed an active vitamin D analogue (normal range 60-120pmol/L). Cholecalciferol supplementation normalised both serum 25(OH)D3 and 1,25(OH)2D3 and significantly increased 24,25(OH)2D3 (Table 1). Conclusion Synthesis of 1,25(OH)2D3 is maintained (in kidney failure) but is substrate dependent, and low serum 25(OH)D was evident at baseline. 1,25(OH)2D3 deficiency is therefore partly a consequence of 25(OH)D deficiency, rather than solely due to elevated FGF23 and reduced renal 1α-hydroxylase activity (which is shown to be present in kidney failure). Cholecalciferol supplementation increases the inactive substrate 25(OH)D3 rather than directly increasing 1,25(OH)2D3. Increases in 25(OH)D3 and 24,25(OH)2D3 are disproportionate to 1,25(OH)2D3 increases, demonstrating the known tight regulation of 1,25(OH)2D3 synthesis and secretion (in response to calcium and parathyroid hormone). Conventional oral vitamin D supplementation may provide a cheap and safe strategy for the management of vitamin D homeostasis in chronic kidney disease.