[Improved outcome with sirolimus-cyclosporine regimen in high-risk renal transplant recipients].
OBJECTIVE
The immunosuppressive agents have a broad spectrum of adverse effects. In the absence of selective and specific drugs the decrease incidence and severity of side effects can be achieved by the combination of synergistic drugs only. Without wise selection and use of the combination of the potent immunosuppressive agents for the immunosuppressive maintenance therapy better results cannot be achieved without or fewer toxicities particularly in high-risk patients who lose their grafts prematurely. Therefore, a good combination will allow not only to reduce individual immunosuppressive drug induced toxicities but will also allow to achieve better graft and patient survival.


METHODS
To assess the 6-year impact of a sirolimus-based regimen with, modest exposures to cyclosporine among three ethnic groups with different rejection risk, the authors performed a retrospective analysis of 470 renal transplant recipients who were treated contemporaneously: Group 1, high risk African Americans (n = 122); Group 2, moderate risk Hispanics (n = 132); Group 3, mild risk Caucasians (n = 216). Multivariate models were used to compare the outcomes in Group 1 with those of the other two groups.


RESULTS
The cumulative incidence of acute rejection episodes over the entire follow-up period was similar among the groups: Group 1, 22.0%, Group 2, 24.2% and Group 3, 23.0%. Although there were no significant differences in overall or individual infection rates, Group 1 and 2 recipients displayed a significantly lower incidence of diarrhea at all times during follow-up compared with Group 3. All recipients showed similar rates of lymphocele formation. However, Group 1 displayed a reduced incidence and decreased severity of hypertriglyceridemia than Group 2 or Group 3 (89.3% vs. 97.2% vs. 93.2%), a similar incidence of hypercholesteremia (94.3% vs. 97.2% vs. 98.5%) was observed. The occurrence of post-transplant diabetes mellitus was greater in Group 1. than Group 3. but similar to Group 2.


CONCLUSIONS
A concentration-controlled sirolimus-cyclosporine-prednisone regimen (with steroid withdrawal by 3 months) reduced the incidence of acute rejection episodes and increased 6-year graft survivals among high-risk African Americans to rates similar to other ethnic groups without an augmented toxicity profile.
Podder
Hemangshu
H
Division of Immunology and Organ Transplantation, The University of Texas Medical School at Houston, Houston, Texas 77030, USA. Hemangshu.podder@uth.tmc.edu
Forgács
Bence
B
Csapó
Zsolt
Z
Kahan
Barry
B
D000208:Acute Disease; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015994:Incidence; D007239:Infections / Q000453:epidemiology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D020123:Sirolimus / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013781:Texas / Q000453:epidemiology; D016896:Treatment Outcome; D044465:White People / Q000706:statistics & numerical data
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus