Features of calcium-phosphorus metabolism and vitamin D metabolism in patients with chronic kidney disease at predialysis stages during bolus cholecalciferol therapy

Background. Chronic kidney disease (CKD) is associated with disturbances in calcium-phosphate homeostasis and vitamin D metabolism, leading in mineral and bone disorders (CKD-MBD). However, the pathogenetic features of these alterations at predialysis CKD stages and the effects of high-dose cholecalciferol therapy remain insufficiently characterized.

Objective. To compare vitamin D metabolites and calcium-phosphate metabolism parameters in patients with predialysis CKD and individuals without impaired kidney function, and to assess their dynamics after a single bolus dose of 150,000 IU of cholecalciferol.

Materials and Methods. The study included 58 participants: 23 patients with CKD stage C3, 14 with CKD stages C4-5, and 21 controls. Parameters of calcium-phosphate metabolism and vitamin D metabolites were assessed at baseline and 7 days after a single oral dose of aqueous cholecalciferol (150,000 IU). Vitamin D metabolites were measured using LC–MS/MS.

Results. Data are presented as follows: control group, CKD C3, CKD C4-5. At baseline, CKD patients had higher parathyroid hormone (PTH) levels (51.3 [40.6; 62.7] vs 70.9 [49.0; 105.9] vs 101.0 [91.7; 120.1] pg/mL), lower calcitriol concentrations (40.9 [34.3; 59.4] vs 25.0 [19.8; 29.1] vs 26.4 [13.8; 30.6] pg/mL), a trend toward higher fibroblast growth factor 23 (FGF-23) levels (0.73 [0.43; 1.07] vs 1.08 [0.61; 2.52] vs 3.22 [1.78; 4.51] pmol/L), and a reduced 24,25 (OH)₂D₃/25(OH)D₃ ratio (0.06 [0.04; 0.08] vs 0.03 [0.01; 0.04] vs 0.03 [0.02; 0.04]), indicating impaired 24-hydroxylase activity. Total and free 25(OH)D levels and vitamin D-binding protein (VDBP) were comparable between groups.

Seven days after cholecalciferol administration, a similar increase in total 25(OH)D₃, 3-epi-25(OH)D₃, and 24,25(OH)₂D₃ was observed in all groups. However, the increase in free 25(OH)D was significantly smaller in CKD C3 and C4-5 compared with controls (p=0.036 and p=0.028). PTH decreased in CKD C3 (p=0.039), whereas FGF-23 increased in CKD C4-5 (p=0.042). Serum calcium, phosphorus, calcitriol, and VDBP remained unchanged.

Conclusion. Alterations in calcium-phosphate and vitamin D metabolism at predialysis CKD stages show a sequential pattern. Reduced vitamin D activation and inactivation, increased FGF-23 levels, and a blunted free 25(OH)D response to bolus cholecalciferol indicate specific regulatory features and limit the applicability of standard vitamin D correction regimens in this population.

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