Abstract
Patients requiring liver transplantation (LT) frequently experience renal insufficiency (RI), which affects their survival. Although calcineurin inhibitor-sparing immunosuppressive regimens (CSRs) are well known to prevent RI, the immune state in recipients receiving CSR remains to be intensively investigated. Among 60 cases of living-donor LT at our institute, 68% of the patients had none to mild RI (non-RI group) and 32% of the patients had moderate to severe RI (RI group). The RI group received a CSR comprising reduced dose of tacrolimus, methylprednisolone, and mycophenolate mofetil, while the non-RI group received a regimen comprising conventional dose of tacrolimus and methylprednisolone. One year after LT, the mean estimated glomerular filtration rate (eGFR) in the RI group had significantly improved, although it was still lower than that of the non-RI group. Serial mixed lymphocyte reaction assays revealed that antidonor T-cell responses were adequately suppressed in both groups. Thus, we provide evidence that CSR leads to improvement of eGFR after LT in patients with RI, while maintaining an appropriate immunosuppressive state.
Highlights
Renal insufficiency (RI) has been widely recognized as a serious complication of liver transplantation that significantly compromises patient outcome [1,2,3,4]
Before the liver transplantation (LT), 68% of the patients had none to mild RI and 32% of the patients had moderate to severe RI (RI group; mean estimated glomerular filtration rate (eGFR), 42.5 ± 15.9 mL/min/1.73 m2)
Chronic RI is a serious complication in liver transplantation that significantly compromises patient survival and outcome
Summary
Renal insufficiency (RI) has been widely recognized as a serious complication of liver transplantation that significantly compromises patient outcome [1,2,3,4]. Late renal failure is associated with both pre- and posttransplant factors, including higher concentrations of CNIs both early and late posttransplant and can be predicted by creatinine levels in the first year posttransplant [9, 10] The recognition of these effects induced interest in strategies using a CNI-sparing immunosuppressive regimen (CSR). Current strategies to overcome CNI toxicity include reduction or withdrawal of CNIs concurrent with switching over to less nephrotoxic drugs like the mammalian target of rapamycin (mTOR) inhibitor or mycophenolate mofetil (MMF) [11,12,13,14,15,16,17] These strategies have clearly demonstrated the ability to reduce the incidence of nephrotoxicity in various studies, CSR may result in an increased risk for acute rejection episodes in a subset of patients
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