Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure

Background. In patients with chronic renal failure (CRF), abnormalities in vitamin D metabolism are known to be present, and several factors could contribute to the abnormalities. Methods. We measured serum levels of three vitamin D metabolites, 1,25(OH)(2)D, 24,25(OH)(2)D and 25(OH)D, and analyzed factors affecting their levels in 76 nondialyzed patients with CRF (serum creatinine > 1.6 and < 9.0 mg/dl), 37 of whom had diabetes mellitus (DM-CRF) and 39 of whom were nondiabetic (nonDM-CRF). Results. Serum levels of 1,25(OH)(2)D were positively correlated with estimated creatinine clearance (C-Cr; r = 0.429; P < 0.0001), and levels of 24,25(OH)(2)D were weakly correlated with C-Cr (r = 0.252, P < 0.05); no correlation was noted for 25(OH)D. Serum levels of all three vitamin D metabolites were significantly and positively correlated with serum albumin. Although there were no significant differences in age, sex, estimated C-Cr, calcium acid phosphate between DM-CRF and nonDM-CRF, all three vitamin D metabolites were significantly lower in DM-CRF than in nonDM-CRF. To analyze factors influencing vitamin D metabolite levels, we performed multiple regression analyses. Serum 25(OH)D levels were significantly and independently associated with serum albumin, presence of DM and serum phosphate (R-2 = 0.599; P < 0.0001). 24,25(OH)(2)D levels were significantly and strongly associated with 25(OH)D (beta = 0.772; R-2 = 0.446; P < 0.0001). Serum 1,25(OH)(2)D levels were significantly associated only with estimated C-Cr (R-2 = 0.409; P < 0.0001). Conclusions. These results suggest that hypoalbuminemia and the presence of DM independently affect serum 25(OH)D levels, probably via diabetic nephropathy and poor nutritional status associated with diabetes, and that 25(OH)D is actively catalyzed to 24,25(OH)(2)D in CRF, probably largely via extrarenal 24-hydroxylase. Serum levels of 1,25(OH)(2)D were significantly affected by the degree of renal failure. Thus, this study indicates that patients with CRF, particularly those with DM, should receive supplements containing the active form of vitamin D prior to dialysis.