Introduction: Long-term renal-transplantation outcomes are reportedly impaired by acute and chronic nephrotoxicity caused by calcineurin inhibitors (CNI), while recent renal transplant results have improved remarkably due to progress in the development of immunosuppressive drugs. Everolimus (EVL) belongs to a novel class of immunosuppressive agents, known as mammalian target of rapamycin (mTOR) inhibitor or proliferation signal inhibitor, which allow dose reduction or even complete withdrawal of CNI. mTOR inhibitor, such as EVL appear to exacerbate pre-existing proteinuria and may ameliorate nephrotoxicity caused by CNI. We describe herein one patient showing histological improvement of CNI nephrotoxicity with EVL.
Patient: A 53-year-old, female underwent her third living-donor transplantation. We used cyclosporine (CsA), mycophenolate mofetil (MMF), prednisolone (PSL) and basiliximab. Diuresis was obtained immediately, but on post-operative day 3 (POD 3), urine volume decreased and renal function gradually deteriorated. On POD 14, renal biopsy (BTx) revealed CsA-induced nephrotoxicity. Renal function improved with a reduction in the CsA dose, and the patient was subsequently discharged on POD 30 with a serum creatinine level (S-Cr) 1.07 (mg/dL). Acute r rejection occurred three times, but each time renal function was improved by anti-rejection therapy, and subsequently stabilized with S-Cr levels in the 1.4-1.6 range. S-Cr suddenly rose to 4.03 on POD 293. Histopathological examination showed CsA nephrotoxicity. Although we reduced the CsA dose, her renal function remained unstable. We changed CsA to EVL on POD 341, and renal function subsequently stabilized. On POD 420, her S-Cr level was 1.17, and BTx showed amelioration of nephrotoxicity findings.
Conclusion: In this patient, we obtained improvement of renal dysfunction caused by CsA nephrotoxicity without rejection by switching CsA to EVL (EVL +MMF+PSL). EVL can be safely used as an alternative to CsA, and it is anticipated that EVL+MMF+PSL will become one of the choices for immunosuppressive therapy in the future.
Koichi Kozaki, Kenji Yuzawa and Haruo Ohtani