Low serum 1,25(OH)2D3 in end stage renal disease - is reduced 1α-hydroxylase the only problem?
2021
Low serum 1,25-dihydroxyvitamin D (1,25(OH)2D) in end stage renal disease (ESRD) is considered a consequence of elevated fibroblast growth factor 23 (FGF23) and concomitant reduced activity of renal 1α-hydroxylase (CYP27B1). Current ESRD treatment strategies to increase serum calcium and suppress secondary hyperparathyroidism involve supplementation with vitamin D analogues that circumvent 1α-hydroxylase. This overlooks the potential importance of 25-hydroxyvitamin D (25(OH)D) deficiency as a contributor to low serum 1,25(OH)2D. We investigated the effects of vitamin D (cholecalciferol) supplementation (40,000IU for 12 weeks and maintenance dose of 20,000IU fortnightly), on multiple serum vitamin D metabolites (25(OH)D, 1,25(OH)2D3 and 24,25(OH)2D3) in 55 haemodialysis patients. Baseline and 12 month data were compared using related-samples Wilcoxon signed rank test. All patients remained on active vitamin D analogues as part of routine ESRD care. 1,25(OH)2D3 levels were low at baseline (normal range 60-120pmol/L). Cholecalciferol supplementation normalised both serum 25(OH)D and 1,25(OH)2D3. Median serum 25(OH)D increased from 35.1nmol/L (IQR 23.0-47.5nmol/L) to 119.9nmol/L (IQR 99.5-143.3nmol/L) (P<0.001). Median serum 1,25(OH)2D3 and 24,25(OH)2D3 increased from 48.3pmol/L (IQR 35.9-57.9pmol/L) and 3.8nmol/L (IQR 2.3-6.0nmol/L) to 96.2pmol/L (IQR 77.1-130.6pmol/L) and 12.3nmol/L (IQR 9-16.4pmol/L), respectively (P<0.001). A non-significant reduction in daily active vitamin D analogue dose occurred, 0.79mcg at baseline to 0.64mcg at 12 months (P=0.73). The ability to synthesise 1,25(OH)2D3 in ESRD is maintained but is substrate dependent, and serum 25(OH)D was a limiting factor at baseline. Therefore, 1,25(OH)2D3 deficiency in ESRD is partly a consequence of 25(OH)D deficiency, rather than solely due to reduced 1α-hydroxylase activity as suggested by current treatment strategies.
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