Prospective observational study of sirolimus as primary immunosuppression after renal transplantation.
BACKGROUND.: Sirolimus (SRL) is an important component of clinical immunosuppression in renal transplantation, but few international studies have examined how this agent is used in routine practice. METHODS.: Within a large prospective pharmacoepidemiological study, 718 de novo renal graft recipients treated with SRL in 65 centers in 10 countries were monitored for up to 5 years posttransplant to compare the principal outcomes and adverse effects by treatment regimen. RESULTS.: Principal treatment regimens were SRL without a calcineurin inhibitor (33%), SRL+cyclosporine A (CsA) (33%), and SRL+tacrolimus (TAC) (34%); 18% of subjects discontinued SRL, 124/718 (17%) developed biopsy-confirmed acute rejection (BCAR), 64/718 (9%) lost their graft, and 50/718 (7%) died during follow-up. Calculated creatinine clearance was 66+/-26 mL/min at 2 years. The most common adverse events were hypertension, hyperlipidemia, anemia, urinary tract infections, and diabetes. BCAR was significantly lower in subjects receiving SRL+TAC (hazard ratio [HR] 0.46, P=0.009) but not significantly lower in those receiving SRL+CsA (HR 0.62, P=0.102) compared with SRL without a calcineurin inhibitor. Graft loss or death did not significantly differ between treatment groups but were associated, respectively, with deceased donor grafts (HR 3.33, P<0.001) and increased age (HR 1.04, P<0.001). No improvement was observed in patients receiving mycophenolate mofetil in any treatment combination (HR 0.80, P=0.438 for BCAR; HR 0.93, P=0.849 for graft loss; and HR 0.75, P=0.531 for death). CONCLUSIONS.: SRL is most commonly used in combination with mycophenolate mofetil, CsA, or TAC. BCAR was least common in subjects receiving SRL+TAC, but other outcomes seemed comparable between the treatment regimens in routine practice.
Indiana University School of Medicine, Indianapolis, IN, USA. mpescov@iupui.edu
Mark D
MD
Pescovitz
Nosratollah
N
Nezakatgoo
Marc I
MI
Lorber
Bjorn
B
Nashan
Helio
H
Tedesco-Silva
Bertram L
BL
Kasiske
Federico J Juarez
FJ
de la Cruz
Graeme
G
Russ
Joseph
J
Campistol
Paul A
PA
Keown
D000465:Algorithms; D000740:Anemia / Q000139:chemically induced; D015331:Cohort Studies; D003404:Creatinine / Q000378:metabolism; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D006973:Hypertension / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D008137:Longitudinal Studies; D015588:Observer Variation; D011446:Prospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D014552:Urinary Tract Infections / Q000139:chemically induced
D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus; D016559:Tacrolimus