title: Limitations of current liver transplant immunosuppressive regimens: renal considerations.
abstract: BACKGROUND
  The use of calcineurin inhibitor (CNI)-based immunosuppressive regimens following liver transplantation (LTx) has improved the outcomes of the recipients. However, CNI has nephrotoxicity and causes short- and long-term renal complications. The progressive structural changes can be irreversible in the long-term, leading to chronic kidney dysfunction. The present review was to evaluate the different strategies of CNI application to renal function in liver recipients.
  
  
  METHODS
  PubMed database was searched for relevant articles in English on the issue of immunosuppressive regimen and kidney injury that related to early minimization of CNI after LTx.
  
  
  RESULTS
  Total avoidance of CNI from post-LTx immunosuppressive regimens has been associated with unacceptable high rates of acute, steroid resistant rejections; late conversion from CNI to non-nephrotoxic immunosuppressant failed to recover renal function. Early CNI minimization and conversion to non-nephrotoxic immunosuppressant, although had no effect on patient survival rates, improved glomerular filtration rate. The combination of everolimus (a mammalian target of rapamycin inhibitor) and tacrolimus not only maintains immunosuppressive efficacy but also minimizes kidney injury.
  
  
  CONCLUSIONS
  Up to now, protocols entirely avoiding CNI have not passed the primary safety endpoint of patient and graft survival, as well as the FDA mandated endpoint of biopsy proven acute rejection. Thus, early CNI minimization after LTx is the most rational approach preserving post-transplant renal function.
authors.affiliation: Division of Transplant Surgery, University of Chicago, Chicago 60637, USA. jfung@surgery.bsd.uchicago.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: Fung
mesh_terms: D065095:Calcineurin Inhibitors / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016031:Liver Transplantation / Q000009:adverse effects; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents