title: Conversion to sirolimus-based maintenance immunosuppression using daclizumab bridge therapy in renal transplant recipients.
abstract: BACKGROUND
  Conversion from calcineurin inhibitor (CI)-based maintenance immunosuppression to sirolimus (SRL)-based immunosuppression may be beneficial in selected renal transplant recipients. The purpose of this study was to evaluate the safety and efficacy of a daclizumab (DAC) bridge protocol in patients converted from CI- to SRL-based maintenance immunosuppression.
  
  
  METHODS
  We conducted a retrospective chart review of renal transplant recipients who were converted to SRL at least 2 months post-transplant. The protocol consisted of an abrupt discontinuation of either cyclosporin (CsA) or tacrolimus (TAC), initiation of SRL within 48 h of CI discontinuation, and DAC 2 mg/kg at the time of CI discontinuation and again at 14 d (depending on the SRL serum concentration). The SRL starting dose was based on risk stratification in each patient.
  
  
  RESULTS
  Twenty-one renal transplant patients were converted to SRL (11 from TAC, 10 from CsA) between October 2001 and July 2003. Conversion occurred at a mean of 23 months post-transplant. Indications for SRL conversion included 12 for chronic allograft nephropathy (CAN), four for CI-associated neurotoxicity, two for thrombotic microangiopathy (TMA), two for post-transplant diabetes mellitus (PTDM), and one for polyomavirus interstitial nephritis (PVN). Mean follow-up was 16 months from time of conversion. Therapeutic SRL levels were reached at a mean of 14 d. Total serum cholesterol levels increased from a mean of 205 (+/- 47) to 234 (+/- 55) mg/dL (P = 0.014), and serum triglyceride levels increased from a mean of 186 (+/- 66) to 257 (+/- 88) mg/dL (P = 0.002). In addition, mean haemoglobin level decreased from 12.0 (+/- 2.3) to 10.5 (+/- 2.1) g/dL (P = 0.002); total white blood cell count decreased from 8300 (+/- 4300) to 4700 (+/- 1400)/mm(3) (P < 0.001); and platelet count decreased from 238 000 (+/- 72 800) to 186 000 (+/- 51 900)/mm(3) (P = 0.002) from before to after conversion. Patients experienced the following side-effects while taking SRL: diarrhoea (n = 6), peripheral oedema (n = 5), arthralgias (n = 4), anaemia (n = 4), oral ulcers (n = 1), deep vein thrombosis (n = 1), shortness of breath (n = 1), and mild increase in serum transaminases (n = 1). Two patients (9.5%) discontinued SRL due to side-effects, both secondary to severe arthralgias. There were two serious infections noted after conversion: one Pseudomonas aeruginosa urosepsis, and one PVN (that was ongoing prior to conversion). Patient survival was 100%, and kidney graft survival was 76%. Five patients (24%) lost their allograft after conversion due to progression of CAN (n = 2), persistent TMA in the kidney (n = 1), patient self-discontinuation of sirolimus (n = 1), and preexisting PVN unresponsive to cidofovir therapy (n = 1). Of the five patients who lost their allograft, the mean serum creatinine at the time of conversion was 3.5 (+/-1.1) mg/dL compared with 2.2 (+/- 0.8) mg/dL in patients who did not lose their allograft (P = 0.034). No acute rejection episodes occurred after conversion to sirolimus.
  
  
  CONCLUSIONS
  DAC bridge therapy provides safe and effective immunosuppressive coverage while converting renal transplant recipients from CI- to SRL-based maintenance immunosuppressive therapy. A pharmacoeconomic analysis, however, is necessary to determine the cost-effectiveness of this conversion protocol.
authors.affiliation: Department of Pharmacy, Wake Forest University Baptist Medical Center and School of Medicine, Winston-Salem, NC, USA.
authors.forename: Aimee K
authors.initials: AK
authors.lastname: Sundberg
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rohr
authors.forename: Erica L
authors.initials: EL
authors.lastname: Hartmann
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Adams
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Stratta
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002784:Cholesterol / Q000097:blood; D000077561:Daclizumab; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000097:blood / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D014280:Triglycerides; D002784:Cholesterol; D000077561:Daclizumab; D020123:Sirolimus