Abstract
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.
Highlights
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
Kreis et al and Nankivell et al reported that most renal transplant patients exhibit signs of CNI nephrotoxicity within 1 year of renal transplantation [6,7]
Nankivell et al reported that lowering CNI dose can reduce CNI nephrotoxicity [7]
Summary
With recent progress in immunosuppressive therapy, shortterm transplantation outcomes have improved remarkably. Nephrotoxicity associated with calcineurin inhibitors (CNI) is a challenging problem. As we think about dose reductions and withdrawal of CNI including cyclosporine (CsA), as a means of reducing the nephrotoxicity of CsA in the future, everolimus (EVL), an mTOR inhibitor, is expected to play an important role [1]. EVL has far been used for induction/ maintenance therapy in two cases, and for CsA nephrotoxicity in three others (Table 1). We report our experience with a case of CsA nephrotoxicity that developed after transplantation of a kidney in which renal function was improved by switching from CsA to EVL.
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