Steroid-free immunosuppression after kidney transplantation with antithymocyte globulin induction and cyclosporine and mycophenolate mofetil maintenance therapy.
BACKGROUND
Our goal in clinical renal transplantation is to find immunosuppressive procedures that not only promote long-term patient and graft survival but also improve the overall well-being of the patients.


METHODS
In a retrospective consecutive clinical study with historical controls, 68 patients were discharged from our center with functioning grafts between September 1995 and December 1997. Patients received steroid-free immunosuppression using an initial 10-day antithymocyte globulin induction and maintenance therapy with cyclosporine and mycophenolate mofetil (MMF). No steroids were given.


RESULTS
After an observation for up to 2.5 years (median 488 days, range 127 to 945 days), 66 patients (one died from sepsis after 6 months, and one died of peritonitis after returning to dialysis) were alive and well. Sixty-four grafts were functioning well, hemolytic uremic syndrome recurred in one graft, one graft had to be removed for noncompliance, and two patients returned to dialysis after chronic rejection-one after 8 months (the patient who died in peritoneal dialysis) and one (a third graft in an antibody-positive patient) 16 months after transplantation. We observed only 10 acute rejections (15%), a rate significantly lower (P=0.0006) than the 71 acute rejections observed in 190 previous consecutive transplants (37.4%) treated without MMF but otherwise after exactly the same protocol. In further comparison, the MMF-treated group also showed an equivalent (P=NS) rate of cytomegalovirus infections and a lower rate (P<0.00005) of Epstein-Barr virus infections. Graft function was excellent (median serum creatinine below 200 micromol/L at 1 year), and no malignancies were observed in the MMF-treated patients. Side effects were mainly leukopenia and two gastrointestinal disturbances.


CONCLUSIONS
Our first-line, steroid-free immunosuppressive protocol allows initial graft function, provides a safe level of long-term graft survival and function with a very low rejection rate, gives an acceptable rate of side effects, and possesses the potential for lowering the incidence of chronic rejection over the long-term. Compared with protocols that discontinue steroids after the initial posttransplant period, a steroid-free protocol avoids the increased risk of infection and body disfigurement in the early posttransplant period. It also avoids the long-term risks of steroid use and the increased risks of rejection when the steroids are withdrawn.
Birkeland
S A
SA
Department of Nephrology, Odense University, Denmark. S.A.Birkeland@OUH.DK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid