Lead VITALE investigator Dr Marie Courbebaisse (Paris, France), commented:
Our study shows that currently recommended doses of vitamin D are not sufficient to protect patients from the risk of fracture after kidney transplantation. This challenges advice in the current international KDIGO guidelines, which recommend using low doses of cholecalciferol similar to those recommended for the general population."
Kidney transplant recipients are at increased risk of fracture due to a combination of factors. As the kidneys fail, they are no longer able to maintain normal levels of parathyroid hormone, vitamin D, and blood levels of calcium and phosphate, which are important for bone health. As a result, patients are likely to have renal bone disease--known as chronic kidney disease-mineral bone disease (CKD-MBD) at the time of their transplant; or they may develop the condition if their transplanted kidney has suboptimal function. Some immunosuppressant drugs, given to prevent organ rejection, also have adverse effects on bone health. Current guidelines recommend correction of vitamin D deficiency or insufficiency to help improve bone health, based on guidelines in the general population. However, high-grade evidence to support this recommendation has been lacking.
Vitamin D (cholecalciferol) is the form of vitamin D that is naturally made by the body through exposure to direct sunlight. The aim of the VITALE study was to compare the transplantation. A prospective, multicenter, double-blind, controlled trial, VITALE randomly assigned 536 kidney transplant recipients (mean age 50.8 years, 335 males) to either 100,000 IU (high dose) or 12,000 IU (low dose) cholecalciferol every two weeks for two months, then monthly for 22 months. In the study, 'low dose' corresponded to a minimum recommended intake of 400 UI/day.
After 24 months, vitamin D levels were significantly greater in the high-dose group compared to the low-dose group: 43.1(12.8) ng/mL versus 25.1(7.4) ng/mL compared with 20.2(8.1) versus 19.2(7.0) ng/mL at study inclusion (p<0.0001). The incidence of fractures was significantly lower in the high-dose group (1% versus 4% in the low-dose group; p=0.02). There were, however, no differences between the two groups in the risks of diabetes, major cardiac events (e.g. heart attack), new cases of cancer, or death. High-dose treatment was well tolerated, with no increased risks of vascular calcification or abnormal blood levels of calcium and phosphate (hypercalcemia and hyperphosphatemia, respectively).
Professor Carmine Zoccali, ERA-EDTA President concluded:
The VITALE 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. More broadly, 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."