Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the Rapamune Maintenance Regimen Study.
BACKGROUND
The purpose of this study was to evaluate early cyclosporine (CsA) withdrawal from a sirolimus (SRL)-CsA-steroid (ST) regimen.


METHODS
Within 48 hr after transplantation, 525 primary (90%) or secondary (10%) renal allograft recipients with cadaveric (89%) or living (11%) donors received 2 mg of SRL (troughs >5 ng/mL; immunoassay), CsA, and ST. Those eligible (430) were randomly assigned (1:1) at 3 months +/- 2 weeks to remain on triple-drug therapy (SRL-CsA-ST group) or to have CsA withdrawn and SRL trough concentrations targeted to 20 to 30 ng/mL (SRL-ST group) until month 12, and 15 to 25 ng/mL thereafter.


RESULTS
At 24 months, there were no statistically significant differences in patient survival (94.0% vs. 95.3%), graft survival (91.2% vs. 93.5%), acute rejection after randomization (5.1% vs. 9.8%) or discontinuations (34% vs. 33%) for SRL-CsA-ST versus SRL-ST, respectively. Serum creatinine level was significantly better in patients who had CsA withdrawn (167 vs. 128 micromol/L, P<0.001), as was the slope of 1/creatinine. Similarly, systolic blood pressure was lower in patients who had CsA withdrawn (141 vs. 134 mm Hg, P<0.001). High-density lipoprotein cholesterol was significantly higher in the SRL-ST group, whereas total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were not significantly different. Hypertension, creatinine increase, abnormal kidney function, toxic nephropathy, edema, hyperuricemia, cataracts, Herpes zoster, and malignancy were reported significantly more often in patients continuing CsA. Thrombocytopenia, hypokalemia, abnormal liver function tests, abnormal wound healing, ileus, and pneumonia were reported significantly more frequently with SRL-ST.


CONCLUSIONS
Data at 2 years confirm that early CsA withdrawal followed by an SRL-ST maintenance regimen results in long-term improvement in both renal function and blood pressure, without increased risk of graft loss or late acute rejection.
Oberbauer
Rainer
R
Innere Medizin III-Nephrologie, Allgemeines Krankenhaus, Vienna, Austria. rainer.oberbauer@akh-wien.ac.at.
Kreis
Henri
H
Johnson
Robert W G
RW
Mota
Alfredo
A
Claesson
Kerstin
K
Ruiz
Juan Carlos
JC
Wilczek
Henryk
H
Jamieson
Neville
N
Henriques
Antonio C
AC
Paczek
Leszek
L
Chapman
Jeremy
J
Burke
James T
JT
D001794:Blood Pressure; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000401:mortality; D006085:Graft Survival / Q000187:drug effects; D006454:Hemoglobins; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D006454:Hemoglobins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D020123:Sirolimus