Conversion to sirolimus‐based maintenance immunosuppression using daclizumab bridge therapy in renal transplant recipients
Authors: Sundberg Aimee K , Rohr Michael S , Hartmann Erica L , Adams Patricia L , Stratta Robert J 
Published: June 2004

Abstract:  Introduction:  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)/mm3 (P < 0.001); and platelet count decreased from 238 000 (± 72 800) to 186 000 (± 51 900)/mm3 (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.