Cholecalciferol Supplementation and Transplant Outcomes Across Immunosuppressive Regimens in Renal Transplant Recipients Using the United States Food and Drug Administration Adverse Event Reporting System

Background Renal transplant recipients (RTRs) are highly susceptible to vitamin D deficiency because of chronic kidney disease and recommendations for sun avoidance. Cholecalciferol supplementation is frequently prescribed in combination with immunosuppressive therapy; however, comparative safety and efficacy profiles across immunosuppressive regimens remain insufficiently characterized. Objectives This study evaluated disproportionality in the reporting of transplant outcome events associated with cholecalciferol supplementation among RTRs receiving different immunosuppressive regimens, using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methodology FAERS data (2004Q1-2025Q4) were analyzed to identify RTRs with and without cholecalciferol exposure. To minimize confounding from concomitant medications, comparisons were restricted to regimen pairs differing only in cholecalciferol inclusion. Reporting odds ratios (RORs) and adjusted RORs (aRORs) were calculated using univariate and multivariate logistic regression to evaluate disproportionate reporting of transplant outcome events (e.g., complications of transplanted kidney, graft dysfunction, graft loss, rejection). Results Among 26,002 RTRs, cholecalciferol-added regimens were compared with their cholecalciferol-naive counterparts within each immunosuppressive regimen. In the calcineurin inhibitor (CNI) + steroid (STR) + antimetabolite (ANT) regimen, cholecalciferol addition was associated with significantly lower reporting of transplant outcome events than CNI + STR + ANT without cholecalciferol (ROR: 0.565 (95% confidence interval (CI): 0.382-0.836), P = 0.004; aROR: 0.589 (95% CI: 0.392-0.885), P = 0.011). Similarly, in the CNI + STR regimen, cholecalciferol addition was associated with significantly lower reporting of transplant outcome events than CNI + STR without cholecalciferol (ROR: 0.297 (95% CI: 0.093-0.950), P = 0.041; aROR: 0.306 (95% CI: 0.095-0.981), P = 0.046). In contrast, for the CNI + STR + ANT + monoclonal antibody (MAB) regimen, cholecalciferol addition was associated with higher reporting of transplant outcome events than with CNI + STR + ANT + MAB without cholecalciferol (ROR: 1.683 (95% CI: 1.004-2.823), P = 0.048; aROR: 1.871 (95% CI: 1.106-3.165), P = 0.019). Conclusions This FAERS analysis indicates that cholecalciferol supplementation is associated with differential reporting patterns of transplant outcome events across immunosuppressive regimens in RTRs. Lower reporting was observed in base regimens lacking monoclonal antibodies, while higher reporting emerged in monoclonal antibody-containing regimens. These hypothesis-generating findings highlight the need for confirmation through well-designed prospective studies.