The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study

BACKGROUND: Prediction of acute kidney transplant rejection remains imperfect despite several known risk factors. There is an increasing appreciation of the potential importance of the vitamin D pathway in immunological disease and transplantation. OBJECTIVE: The purpose of this study was to determine the association of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with acute rejection. DESIGN: This was a prospective cohort study. SETTING: Three academic adult kidney transplant programs in Ontario, Canada, were chosen. PATIENTS: All consecutive adult patients at the 3 institutions who received a solitary kidney transplant, were able to provide written informed consent, and planned to be followed at the same center post-operatively were included. MEASUREMENTS: Serum concentration of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured at baseline, 3, and 6 months post-transplantation. Acute rejection was classified using Banff criteria. METHODS: The co-primary outcome was the association between 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D and time to first occurrence of biopsy-proven acute rejection (BPAR) within the first year after kidney transplantation. Cox proportional hazards models were fitted taking into account the time-varying nature of serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. RESULTS: From 556 screened patients, data on 327 kidney transplant recipients are included. First BPAR occurred in 54 (16.5%) patients. In adjusted Cox proportional hazards models, the serum concentration of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D was not associated with acute renal transplant rejection (hazard ratio 1.00; 95% [confidence interval] CI, 0.87-1.14, per 10 nmol/L increase, and hazard ratio 0.97; 95% CI, 0.84-1.12, per 10 pmol/L increase, respectively). LIMITATIONS: Given the observational design, we cannot rule out the possibility of residual confounding that limited our ability to detect a clinically significant effect of vitamin D metabolites on acute rejection. CONCLUSIONS: A low serum concentration of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D is not associated with an increased risk of acute kidney transplant rejection following kidney transplantation.