Reporting patterns of renal failure associated with immunosuppressant combinations following liver transplantation: a retrospective analysis

Immunosuppressant regimens are essential for preventing graft rejection in liver transplant recipients; however, their use has also been associated with increased reporting of renal failure. This study evaluated disproportional reporting patterns of renal failure associated with immunosuppressant combinations using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

A retrospective signal detection analysis was conducted using FAERS data from 2004 (Q1) to 2024 (Q2). Five exposure groups were defined for each core calcineurin inhibitor (tacrolimus or cyclosporine), administered as monotherapy or combined with mycophenolate mofetil (MMF), prednisone, or everolimus. Reporting odds ratios (RORs) and adjusted RORs were calculated for renal failure outcomes, using the corresponding monotherapy as the reference. Regional subgroup and sensitivity analyses were also performed.

Adding MMF to tacrolimus- or cyclosporine-based regimens was associated with lower disproportional reporting of renal failure versus monotherapy. Regional analyses revealed variability in reporting patterns: MMF-containing regimens showed lower disproportionality in Europe, whereas in North America, the tacrolimus-MMF-prednisone combination demonstrated lower reporting signals. In Latin America and Asia, overall reporting proportions of renal failure were lower, and additional agents did not consistently reduce signals. Sensitivity analyses across renal failure-related preferred terms yielded consistent patterns.

These findings reflect disproportional reporting patterns rather than causal or protective effects and should be interpreted cautiously given inherent FAERS limitations, including missing clinical details and lack of denominator data. The results are hypothesis-generating and warrant further investigation using real-world clinical datasets to better characterize renal safety across immunosuppressant combinations.