High daily doses of cholecalciferol (vitamin D3) may halt progression of secondary hyperparathyroidism (SHPT) in patients with stage 3–4 chronic kidney disease (CKD) without causing hypercalcemia or other adverse effects, Swedish researchers reported.
The finding is from a double-blind study that included 95 patients with stage 3–4 CKD, parathyroid hormone (PTH) levels above 6.8 pmol/L, and calcidiol levels below 75 nmol/L. Per-Anton Westerberg, MD, of Uppsala University, and colleagues randomly assigned patients to receive cholecalciferol 8000 IU/day or placebo for 12 weeks. The primary endpoint was the difference in mean change in intact PTH (iPTH) after 12 weeks.
The cholecalciferol and placebo groups had baseline calcidiol levels of 57.5 and 56.8 nmol/L, respectively, and iPTH levels of 10.9 and 13.1 pmol/L, respectively, the investigators reported online ahead of print in Nephrology Dialysis Transplantation. In the cholecalciferol group, calcidiol increased to 161.6 nmol/L and iPTH levels remained constant (mean change −0.7 pmol/L) at 10.5 pmol/mL. In the placebo arm, calcidiol levels remained stable and iPTH increased (mean change 1.6 pmol/L). The mean change in PTH differed significantly between the study groups. The proportion of patients achieving a 30% decrease in PTH did not differ.
“At least to our knowledge, this is the first sufficiently powered study of high-dose cholecalciferol in CKD to show an effect on SHPT,” Dr Westerberg’s team stated.
All patients in the cholecalciferol arm were calcidiol sufficient (levels greater than 75 nmol/L) at 12 weeks. Mean calcitriol levels rose from 64 to 102 pmol/L in the cholecalciferol group but remained stable at 64 pmol/L in the placebo group. Mean calcium levels remained stable in the cholecalciferol group (2.24 mmol/L at baseline and 2.23 mmol/L at 12 weeks) but decreased from 2.27 to 2.22 mmol/L in the placebo recipients, a significant difference between the groups.
Despite substantial increases in calcidiol and calcitriol, no cases of hypercalcemia developed in the treatment arm, the investigators reported.
Westerberg PA, Sterner G, Ljunggren Ö, et al. High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD stages 3–4: results of a 12-week double-blind, randomized controlled study. Nephrol Dial Transplant 2017; published online ahead of print.