Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure.
BACKGROUND
This study evaluated whether cyclosporine (CsA) could be eliminated from a sirolimus (Rapamune, rapamycin, SRL)-CsA-steroid (ST) regimen at 3 months.


METHODS
This was an open-label study conducted in Europe, Australia, and Canada. Upon enrollment, 525 primary (90%) or secondary (10%) renal allograft recipients with cadaveric (89%) or living (11%) donors received 2 mg of sirolimus (troughs>5 ng/ml), CsA, and steroids. At 3 months+/-2 weeks, eligible patients were randomized (1:1) to remain on SRL-CsA-ST or to have CsA withdrawn and therapy continued with SRL (troughs 20-30 ng/ml)-ST.


RESULTS
At 12 months, overall graft and patient survival were 89.1% and 94.9%, respectively. In the 430 (82%) randomized patients, there was no difference in graft survival (95.8% vs. 97.2%, SRL-CsA-ST vs. SRL-ST) or patient survival (97.2% vs. 98.1%, respectively). The incidence of biopsy-confirmed primary acute rejection was 13.1% during the prerandomization period. After randomization, the acute rejection rates were 4.2% and 9.8% for SRL-CsA-ST and SRL-ST, respectively (P=0.035). Renal function (calculated glomerular filtration rate, 57 vs. 63 ml/min, P<0.001) and blood pressure significantly improved when CsA was withdrawn. Hypertension, CsA nephrotoxicity, hyperuricemia, and Herpes zoster occurred statistically more frequently in patients remaining on CsA, whereas thrombocytopenia, abnormal liver function tests, and hypokalemia were reported more often for SRL-ST therapy.


CONCLUSIONS
Sirolimus, CsA, and steroids for 3 months posttransplant, followed by elimination of CsA, is a safe and effective alternative to continuous therapy with sirolimus, CsA, and steroids that can result in better renal function and lower blood pressure.
Johnson
R W
RW
Manchester Royal Infirmary, The Renal Transplant Unit, Oxford Road, Manchester M13 9WL, UK. rwgj@renal.cmht.nwest.nhs.uk
Kreis
H
H
Oberbauer
R
R
Brattström
C
C
Claesson
K
K
Eris
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013256:Steroids / Q000008:administration & dosage; D015996:Survival Rate
D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D020123:Sirolimus