Decreased Conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 Following Cholecalciferol Therapy in Patients with CKD

Abstract

concentrations were lower in the CKD group; moreover, the absolute increase in 24,25(OH) 2 D 3 after therapy was markedly smaller in patients with CKD (change, 2.8 ng/ml [2.3-3.5 ng/ml] for controls versus 1.2 ng/ml [0.6-1.9 ng/ml] for patients with CKD; P,0.001). Furthermore, higher baseline FGF23 concentrations were associated with smaller increments in 24,25(OH) 2 D 3 for individuals with CKD; this association was negated after adjustment for eGFR by multivariate analysis.Conclusions Patients with CKD exhibit an altered ability to increase serum 24,25(OH) 2 D 3 after cholecalciferol therapy, suggesting decreased 24-hydroxylase activity in CKD. The observed relationship between baseline FGF23 and increments in 24,25(OH) 2 D 3 further refutes the idea that FGF23 directly contributes to 25(OH)D insufficiency in CKD through stimulation of 24-hydroxylase activity.

Assessment of vitamin D status – a changing landscape

“…Its serum concentration strongly depends on the availability of 25-OHD and the expression of CYP24A1. CYP24A1 is, at least in part, regulated by VDR [112,114] [115]. A potential value of VMR in monitoring the effectiveness of vitamin D supplementation has also been shown by others [116].…”

24,25-Dihydroxyvitamin D3 and Vitamin D Status of Community-Dwelling Black and White Americans

“…This ratio should depend primarily upon CYP24A1 expression, which is downregulated in vitamin D deficiency, and thus the VMR would be predicted to decrease in vitamin deficient states. Multiple studies have shown that VMR tends to be disproportionately decreased in patients with low 25D concentrations and in patients who have functional vitamin D deficiency because of chronic kidney disease (CKD) (21–23, 26, 27). Low VMR also may be predictive of responsiveness to vitamin D supplementation (21, 27), and it has been demonstrated that patients with CKD do not increase VMR concentrations in response to vitamin D supplementation as much as control subjects, consistent with the model that defective kidney production of 1,25(OH 2 )D results in a persistent decrease in 24,25(OH) 2 D catabolism (22).…”

Vitamin D Measurement, the Debates Continue, New Analytes Have Emerged, Developments Have Variable Outcomes

“…A ratio of > 80 is associated with patients with heterozygous or biallelic mutations of CYP24A1 [67,69]. Moderate elevation of 25(OH) D:24,25(OH) 2 D VMR due to partial inactivity of CYP24A1 is associated with renal impairment [58,76] and bone disorders [77]. 25(OH)D:24,25(OH) 2 D VMR has an advantage for being less susceptible to seasonal fluctuation [78], allowing interpretation using fixed reference intervals irrespective of the time of the year.…”