Evidence for the Immunosuppressive Potential of Calcineurin Inhibitor-Sparing Regimens in Liver Transplant Recipients with Impaired Renal Function

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.

Significant association between FOXP3 gene polymorphism and steroid‐resistant acute rejection in living donor liver transplantation

“…The basic immunosuppressive regimen used following LDLT has been described . In brief, the immunosuppressive regimen consisted of tacrolimus (TAC) and methylprednisolone (MP) with gradual tapering of the dose.…”

“…As routine Treg analysis had only recently commenced, we analyzed Treg frequency in the patients from our cohort. Tregs were surface stained with the following fluorochrome‐conjugated monoclonal antibodies from BD Pharmingen: peridinin‐chlorophyll protein‐Cyanine5.5 anti‐human CD3 (SK7), allophycocyanin‐conjugated Cyanine7 anti‐human CD4 (RPA‐T4), fluorescein isothiocyanate‐conjugated anti‐human CD25 (M‐A251), PE‐Cyanine7 anti‐human CD45RA (HI100). Intracellular Foxp3 was stained using PE‐conjugated anti‐human Foxp3 (PCH101; eBioscience).…”

“…The basic immunosuppressive regimen used following LDLT has been described. (15)(16)(17) In brief, the immunosuppressive regimen consisted of tacrolimus (TAC) and methylprednisolone (MP) with gradual tapering of the dose. The whole-blood trough level of TAC was maintained between 8 and 15 ng/mL in the first few postoperative weeks and between 5 and 10 ng/ mL thereafter.…”

Molecular Mismatch Predicts T Cell–Mediated Rejection and De Novo Donor‐Specific Antibody Formation After Living Donor Liver Transplantation

“…The clinical suspicion of TCMR was supported by the protocoled MLR assay, which can rigorously monitor rejection. (16)(17)(18) Episodes of rejection…”

Strategies for Deliberate Induction of Immune Tolerance in Liver Transplantation: From Preclinical Models to Clinical Application

“…We have previously reported that optimization of immunosuppressive therapy based on the CFSE-MLR assay provides a low incidence of acute rejection, reduction of infectious complications, and helps in monitoring anti-self-response of CD4 + T cells, which predicts the recurrence of autoimmune liver diseases after LT ( 98 , 100 – 102 ) ( Figure 3B ). In addition, CFSE-MLR-based immune monitoring has been proven to be a useful tool to personalize IS therapy, especially for LT patients with impaired renal function and HBV-infected LT patients requiring post-transplant HBV vaccination ( 103 , 104 ). The benefit of CFSE-MLR immune-monitoring can be applied to T cell receptor (TCR) repertoire analysis by high-throughput sequencing.…”