Tetsuo Shoji, MD, PhD.
Department of Vascular Medicine
Osaka City University Graduate School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Vitamin D is known to be associated with health and disease of various organs such as bone, heart, brain, and others. Vitamin D is activated by the liver and kidneys to a hormone called 1,25-dihydroxyvitamin D which binds to vitamin D receptor in cells to exert its functions.
Vitamin D activation is severely impaired in patients with kidney disease requiring hemodialysis therapy, leading to mineral and bone disorder(MBD). Therefore, active form of vitamin D is one of the standard choices of treatment for MBD caused by kidney function loss.
Previous observational cohort studies showed that the use of active vitamin D in hemodialysis patients was associated with lower likelihood of all-cause death, cardiovascular death, and incident cardiovascular disease.Potentially cardio-protective effects of active vitamin D were shown by basic studies using cultured cells and animal models. Then, many nephrologists began to believe that active vitamin D is a “longevity hormone” or a “panacea” for kidney patients requiring dialysis therapy, although there was no evidence by randomized clinical trials.
To show evidence for it, we conducted a randomized clinical trial namedJ-DAVID in which 976 hemodialysis patients were randomly assigned to treatment with oral alfacalcidol or treatment without active vitamin D, and they were followed-up for new cardiovascular events during the four-year period. The risk of cardiovascular events was not significantly different between the two groups. The risk of all-cause death was not significantly different either.
To our surprise, the risk of cardiovascular event tended to be higher in the patients who continued treatment with active vitamin D than those who continued non-use of active vitamin D, although the difference was not statistically significant.
MedicalResearch.com: What should readers take away from your report?
Response: It is established that active vitamin D sterols are beneficial in the treatment of MBD for patients undergoing hemodialysis. However, this randomized clinical trial showed no evidence for its benefit on longevity or cardiovascular health in this patient group.
It should be noted that we excluded patients with secondary hyperparathyroidism (= who had increased levels of parathyroid hormone) from this trial, because active vitamin D was the only recommended drug for this condition, but one half of the participants of the trial were assigned to no active vitamin D group for four years.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We need to know the reason for the discrepancy between observational studies and this randomized clinical trial. It is possible that there are three subgroups of patients who have different responses to the same treatment; beneficial, neutral, and harmful responses. If we are able to know the subgroup to which our patient belongs in advance, we can choose a beneficial treatment more wisely.
Disclosures: The study was funded by a grant from The Kidney Foundation, Japan. Tetsuo Shoji received research grant and lecture fees from Chugai.
The J-DAVID Investigators. Effectof Oral Alfacalcidol on Clinical Outcomes in Patients Without SecondaryHyperparathyroidism Receiving Maintenance HemodialysisThe J-DAVID RandomizedClinical Trial. JAMA.2018;320(22):2325–2334.doi:10.1001/jama.2018.17749
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