Distinct impact of vitamin D insufficiency on calcitriol levels in chronic renal failure and renal transplant patients: a role for FGF23

Introduction: Vitamin D insufficiency contributes to calcitriol (1,25D) reduction in chronic kidney disease (CKD). Since CKD patients on conservative therapy (CRF) mostly develop, whereas transplant (TX) patients possibly recover from, secondary hyperparathyroidism (SH), we hypothesized a different efficiency of vitamin D hydroxylation in these 2 clinical conditions. Methods: We compared the impact of reduced 25-hydroxyvitamin D (25D) on circulating 1,25D in 111 CRF (mean age 63 ± 15 years; estimated glomerular filtration rate [eGFR] 36.4 ± 22.0 ml/min) and in 136 TX patients (mean age 50 ± 11 years; eGFR 47 ± 19.0 ml/min). Results: Vitamin D insufficient patients (69.1% in TX vs. 82% in CRF; p<0.005), compared with those without insufficiency, had lower values of 1,25D in CRF (24.5 ± 17.4 vs 35.8 ± 17.8 pg/mL; p<0.01) but not in TX (42.7 ± 23.8 vs. 50.1 ± 25.4 pg/mL; p=n.s.). Serum 25D and 1,25D were correlated in both CRF (r=0.387, p<0.0001) and TX (r=0.240, p0<.005) groups, but 1,25D values were higher in the TX group in any of the 4 ranges for 25D considered. Serum calcitriol correlated with eGFR (CRF: r=0.641, p<0.0001; TX: r=0.426, p<0.0001), but again with higher values in the TX group, in any of the CKD stages considered, except stage 2. In both conditions, the most predictive parameter of 1,25D levels was eGFR, together with phosphate and 25D in the CRF group (r2=0.545; p<0.0001), and with Ca and 25D in the TX group (r2=0.345; p<0.0001). In 2 subgroups, comparable for eGFR and 25D, levels of FGF23 were lower in the TX group, in agreement with higher values of 1,25D. Conclusions: A 25D deficit more significantly affects calcitriol concentrations in CRF as compared with TX. Efficiency of vitamin D hydroxylation should be considered when planning vitamin D replacement strategies.