The parathyroid hormone-lowering effect of vitamin D supplementation is inconsistent in patients with chronic kidney disease mineral bone disorder (CKD-MBD), according to the authors of a new systematic review and meta-analysis. Calcifediol and analogues, however, consistently suppressed PTH, but also increased fibroblast growth factor 23 (FGF23), a predictor of vascular calcification and cardiovascular disease (CVD).
In the meta-analysis of 9 randomized controlled trials of patients with mostly stage 3 to 4 CKD, vitamin D supplements including vitamin D3 (cholecalciferol) or D2 (ergocalciferol) significantly increased plasma 25-hydroxyvitamin D(25(OH)D), but only significantly decreased PTH by a mean 17.6 pg/mL in 4 studies, Inez Schoenmakers, PhD, of the University of East Anglia in Norwich, UK, and colleagues reported in Calcified Tissue International. Vitamin D doses varied from 2000 to 4000 IU daily or 40,000 to 50,000 IU weekly for 1 to 12 months.
Calcifediol, calcitriol, and paricalcitol consistently reduced PTH by a significant mean 35 pg/mL, the investigators reported. However, in 3 studies, FGF23 levels increased with analogue administration.
“The increase in FGF23 with analogue administration warrants attention as this hormone is already elevated in CKD patients and is a predictor of vascular calcification and CVD,” according to Dr Schoenmakers’ team. “Its increase may indicate an undesirable side effect of administration of these forms of vitamin D.”
Evidence gaps remain in the management of vitamin D status in CKD-MBD, the investigators emphasized. Comparing guidelines from Kidney Disease Outcomes Quality Initiative (KDOQI) 2003, Kidney Disease Improving Global Outcomes (KDIGO) 2009, and Kidney Health Australia 2012-2013 guidelines, the team formulated a reasonable management scheme, which is detailed in their paper. Briefly, patients with CKD with serum 25(OH)D less than 75 nmol/L can initiate vitamin D2 or D3 supplementation and undergo serum calcium and phosphorus monitoring every 3 months. If serum PTH still exceeds the upper limit of the assay, clinicians can initiate 1,25(OH)2D or analogue treatment. Restriction of dietary phosphate or an increase in phosphate binders might be beneficial in some cases.
Christodoulou M, Aspray TJ, Schoenmakers I. Vitamin D supplementation for patients with chronic kidney disease: a systematic review and meta-analyses of trials investigating the response to supplementation and an overview of guidelines. Calcif Tissue Int. Published online April 25, 2021. doi:10.1007/s00223-021-00844-1