Free 25-hydroxyvitamin-D concentrations are lower in children with renal transplant compared with chronic kidney disease

Abstract

Background Total serum 25-hydroxyvitamin D [25(OH)D] is considered the best marker of vitamin D status and used routinely in clinical practice. However, 25(OH)D is predominantly bound to vitamin D-binding protein (VDBP), and it has been reported that the free-25(OH)D and 25(OH)D loosely bound to albumin fraction correlates better with clinical outcomes. Methods We assessed total-25(OH)D, measured free-25(OH)D, and calculated free-25(OH)D and their relationship with VDBP and biomarkers of mineral metabolism in 61 children (22 CKD 2-3, 18 dialysis, and 21 post-transplant). Results Total-25(OH)D concentrations were comparable across the three groups (p = 0.09), but free-and bioavailable-25(OH)D (free-and albumin-25(OH)D) were significantly lower in the transplant group (both: p = 0.01). Compared to CKD and dialysis patients, the transplant group had significantly higher VDBP concentrations (p = 0.03). In all three groups, total-25(OH)D concentrations were positively associated with measured free-, calculated free-, and bioavailable-25(OH)D. Multivariable regression analysis showed that total-25(OH)D was the only predictor of measured free-25(OH)D concentrations in the dialysis group (β = 0.9; R 2 = 90%). In the transplant group, measured free-25(OH)D concentrations were predicted by both total-25(OH)D and VDBP concentrations (β = 0.6, − 0.6, respectively; R 2 = 80%). Correlations between parathyroid hormone with total-25(OH)D and measured and calculated free-25(OH)D were only observed in the transplant group (all: p < 0.001). Conclusions In transplanted patients, VDBP concentrations were significantly higher compared to CKD and dialysis patients, and consequently, free-25(OH)D concentrations were lower, despite a comparable total-25(OH)D concentration. We suggest that free-25(OH)D measures may be required in children with CKD, dialysis, and transplant, with further research required to understand its association with markers of mineral metabolism.

Association between 25(OH) vitamin D and graft survival in renal transplanted children

“…Our study has several limitations: the small number of patients (123 children), the absence of mGFR values at 12 months in 37% of patients and the short follow‐up time. Total 25‐OH‐D may be a limitation of our study, a very recent publication conducted in kidney transplanted children found that vitamin D‐binding protein (VDBP) levels were significantly higher in transplanted patients compared to patients with chronic renal failure or dialysis, so free 25‐OH‐D would be lower than total vitamin D levels 58 . This dosage is still only used in clinical research, not available in current practice.…”

“…one-year post-transplant follow-up is probably too short to demonstrate the effect of vitamin D on graft survival and on fibrosis: vitamin D is a hormone subject to wide variations according to diet, sun exposure, and supplements, so its dosage at 3 months might not accurately reflect its overall exposure over the next 9 months.Our study has several limitations: the small number of patients (123 children), the absence of mGFR values at 12 months in 37% of patients and the short follow-up time. Total 25-OH-D may be a limitation of our study, a very recent publication conducted in kidney transplanted children found that vitamin D-binding protein (VDBP) levels were significantly higher in transplanted patients compared to patients with chronic renal failure or dialysis, so free 25-OH-D would be lower than total vitamin D levels 58. This dosage is still only used in clinical research, not available in current practice.…”

Changes in Vitamin D Biomarkers According to the Cause-Glomerular Filtration Rate Albuminuria Classification in Patients with Chronic Kidney Disease

“…Bioavailable 25(OH)D is approximately 10-15% of total 25(OH)D, which is loosely bound to albumin. Meanwhile, free 25(OH)D is not bound to any protein and accounts for approximately 1% of the total 25(OH)D. Some studies suggest that bioavailable or free 25(OH)D may be useful in assessing vitamin D status [13,14]. However, evidence for its potential as an MBD marker in CKD is insu cient.…”