title: A pilot protocol of a calcineurin-inhibitor free regimen for kidney transplant recipients of marginal donor kidneys or with delayed graft function.
abstract: The worsening shortage of cadaver donor kidneys has prompted use of expanded or marginal donor kidneys (MDK), i.e. older age or donor history of hypertension or diabetes. MDK may be especially susceptible to calcineurin-inhibitor (CI) mediated vasoconstriction and nephrotoxicity. Similarly, early use of CI in patients with delayed graft function may prolong ischaemic injury. We developed a CI-free protocol of antibody induction, sirolimus, mycophenolate mofetil, and prednisone in recipients with MDK or DGF.
  
  
  METHODS
  Adult renal transplant recipients who received MDK or had DGF were treated with a CI-free protocol consisting of antibody induction (basiliximab or thymoglobulin), sirolimus, mycophenolate mofetil, and prednisone. Serial biopsies were performed for persistent DGF. Patients were followed prospectively with the primary endpoints being patient and graft survival, biopsy-proven acute rejection, and sirolimus-related toxicity.
  
  
  RESULTS
  Nineteen recipients were treated. Mean follow-up was 294 days. Actuarial 6- and 12-month patient survival was 100% and 100% and graft survival was 93% and 93%, respectively. The only graft loss was due to primary non-function (PNF). The incidence of AR was 16%. Mean serum creatinine at last follow-up was 1.6 mg/dL. Sirolimus-related toxicity included lymphocele (1), wound infection (2), thrombocytopenia (1). and interstitial pneumonitis (1).
  
  
  CONCLUSIONS
  A CI-free protocol with antibody induction and sirolimus results in low rates of AR and PNF and excellent early patient and graft survival in patients with MDK and DGF. CI-free protocols may allow expansion of the kidney donor pool by encouraging utilization of MDK at high risk for DGF or CI-mediated nephrotoxicity.
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. david.schaffer@vanderbilt.edu
authors.forename: David
authors.initials: D
authors.lastname: Shaffer
authors.forename: Anthony
authors.initials: A
authors.lastname: Langone
authors.forename: William A
authors.initials: WA
authors.lastname: Nylander
authors.forename: Simin
authors.initials: S
authors.lastname: Goral
authors.forename: A Tarik
authors.initials: AT
authors.lastname: Kizilisik
authors.forename: J Harold
authors.initials: JH
authors.lastname: Helderman
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D002985:Clinical Protocols; D016572:Cyclosporine / Q000009:adverse effects; D005260:Female; D006084:Graft Rejection / Q000628:therapy*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000139:chemically induced*; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010865:Pilot Projects; D011241:Prednisone / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus; D016559:Tacrolimus