BUDAPEST, Hungary — High doses of vitamin D₃ are safe and more effective in preventing bone fracture in kidney transplant recipients than standard recommended doses, according to the results of the VITALE (NCT01431430) study.
“Currently recommended doses of vitamin D are not sufficient to protect patients,” said Marie Courbebaisse, MD, PhD, from Hôpital Européen Georges Pompidou in Paris.
“Our findings challenge advice in the current international KDIGO guidelines, which recommend using low doses of cholecalciferol, similar to those recommended for the general population,” she said during a news conference here at the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) 56th Congress.
Vitamin D insufficiency is common in patients who have undergone kidney transplant because their intake is inadequate, their vitamin D catabolism is elevated, and they limit sun exposure to reduce the risk for skin cancer induced by antirejection therapies, Courbebaisse explained.
This study is important for nephrologists and their patients “because it shows that high-dose vitamin D is an effective way of lowering the rate of fractures after kidney transplantation, with a very low risk of any side effects,” said ERA-EDTA President Carmine Zoccali, MD, from Ospedali Riuniti, Reggio Calabria, Italy.
All participants in VITALE had undergone kidney transplant in the previous 12 to 48 months and had serum 25-hydroxyvitamin D concentrations (25[OH]D) below 30 ng/mL. In patients with chronic kidney disease, 25(OH)D levels should exceed 40 ng/mL, according to the Endocrine Society.
The 536 patients were randomized to cholecalciferol — either 12,000 IU or 100,000 IU — every other week for 2 months, and monthly thereafter for 22 months. They were then followed for 24 months.
During the 22-month maintenance phase, the low dose was equivalent to about 400 IU/day and the high dose was equivalent to about 3300 IU/day.
At baseline, 25(OH)D levels were similar in the low- and high-dose groups (19.2 vs 20.2 ng/mL), as was daily calcium intake.
At 24 months, 25(OH)D levels were significantly higher in the high-dose group than in the low-dose group (43.1 vs 25.1 ng/mL; P < .0001). However, there was no difference in the number of composite end-point events in the high- and low-dose groups (15% vs 16%).
“Importantly, the incidence of each item in the primary end point was not significantly different between the two groups,” Courbebaisse reported.
There were also no significant differences in infection rates between the high- and low-dose groups (51% vs 47%) or in acute rejection episodes (3% vs 2%). And rates of graft loss were identical in the two groups, at 0.37%.
However, the risk for symptomatic fracture was significantly lower in the high-dose group than in the low-dose group (1% vs 4%; odds ratio, 0.24; P = .02).
Serum parathyroid hormone concentrations decreased from baseline to month 24 in the high-dose group (77 vs 71 pg/mL; P < .05), but remained stable in the low-dose group throughout the study period (77 vs 78 pg/mL).
There were also no differences in the incidence of hypercalcemia in the high- and low-dose groups (17% vs 13%), the incidence of hyperphosphatemia (5% vs 4%), or in the urinary calcium to creatinine ratio.
“After renal transplantation, high doses of cholecalciferol are well tolerated and they do not increase the risk of extraskeletal complications, compared with the minimally recommended intake of vitamin D for the general population,” said Courbebaisse.
“Recommendations should be rewritten, as we now know, thanks to this study, that to obtain sufficient vitamin D levels after renal transplantation, we obviously have to increase the dose,” she said.
“More broadly,” Zoccali added, “we see, yet again, that other benefits for vitamin D seen in observational studies are not reflected when supplementation is tested in randomized controlled trials.”
Courbebaisse and Zoccali have disclosed no relevant financial relationships.