A pilot study of steroid-free immunosuppression in the prevention of acute rejection in renal allograft recipients.
BACKGROUND
Corticosteroids have been a mainstay of rejection prophylaxis for several decades, despite the multiple adverse effects of long-term use, including weight gain, hyperlipidemia, diabetes, hypertension, and bone disease. The detrimental effect of steroids on the metabolic profile begins in the early posttransplantation period, and the complete avoidance of steroids in transplantation would therefore be optimal. We hypothesized that the addition of mycophenolate mofetil (MMF) and a humanized monoclonal anti-CD25 antibody (daclizumab) to a cyclosporine (CsA microemulsion)-based immunosuppression protocol would permit transplantation without steroids.


METHODS
Steroid-free renal transplantation was attempted in 57 patients treated with daclizumab, MMF, and CsA. Twenty-eight patients received kidneys from living donors; the remaining 29 received cadaveric grafts.


RESULTS
At 1 year, patient and graft survival were 95% and 89%, respectively. Fourteen patients (25%) experienced rejections, of which 13 were readily reversed with steroids; 1 patient required OKT3. Mean serum creatinine at 12 months for patients not experiencing rejection was 149+/-58 micromol/L, compared with 158+/-102 micromol/L for those experiencing rejection. Five patients required hospitalization for infection; no patients developed lymphoproliferative disease. At baseline, 17 patients required 3 or more antihypertensive medications, compared with 2 patients at 1 year. Three of 43 nondiabetic patients developed diabetes during the study. There was no significant reduction in lumbar or femoral bone density.


CONCLUSIONS
On the basis of these positive results, we believe steroid avoidance with this immunosuppressive regimen merits further study.
Cole
E
E
Division of Nephrology, University of Toronto, 621 University Avenue, Norman Urquhart Wing 10-158, Toronto, Canada M5G 2C4. edward.cole@uhn.on.ca
Landsberg
D
D
Russell
D
D
Zaltzman
J
J
Kiberd
B
B
Caravaggio
C
C
Vasquez
A R
AR
Halloran
P
P
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000959:Antihypertensive Agents / Q000008:administration & dosage; D002985:Clinical Protocols; D016572:Cyclosporine / Q000008:administration & dosage; D000077561:Daclizumab; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000008:administration & dosage; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010865:Pilot Projects; D011446:Prospective Studies; D015996:Survival Rate
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000077561:Daclizumab; D009173:Mycophenolic Acid