Simultaneous corticosteroid avoidance and calcineurin inhibitor minimization in renal transplantation.
Steroids and calcineurin inhibitors (CNI) have been mainstays of immunosuppression but both have numerous side effects that are associated with substantial morbidity and mortality. This study was carried out to determine if steroids can be eliminated with early discontinuation of cyclosporine A (CsA) and later discontinuation of mycophenolate mofetil (MMF). Ninety-six patients with kidney transplants were entered into four subgroups of two pilot studies. All patients received Thymoglobulin induction, rapamycin (RAPA), and the immunonutrients arginine and an oil containing omega-3 fatty acids. Mycophenolate mofetil was started in standard doses and discontinued by 2 years. CsA was given in reduced doses for either 4, 6, or 12 months. Follow-up was 12-36 months. Thirteen first rejection episodes occurred during the first year (14%). Combining all patients, 86% were rejection-free at 1 year, 80% at 2 years and 79% at 3 years. No kidney has been lost to acute rejection. Ninety percent of the 84 patients at risk at the end of the study were steroid-free and 87% were off CNI. Fifty-seven percent of 54 patients with a functioning kidney at 3 years were receiving monotherapy with RAPA. We conclude that this therapeutic strategy is worthy of a prospective multi-center clinical trial.
Department of Surgery, Transplantation Division, University of Cincinnati College of Medicine, OH 45267, USA.
J Wesley
JW
Alexander
Hope R
HR
Goodman
Michael
M
Cardi
Joe
J
Austin
Sharad
S
Goel
Shahzad
S
Safdar
Shaoming
S
Huang
Rino
R
Munda
James P
JP
Fidler
Joseph F
JF
Buell
Michael
M
Hanaway
Brian
B
Susskind
Prabir
P
Roy-Chaudhury
Jennifer
J
Trofe
Rita
R
Alloway
E Steve
ES
Woodle
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001120:Arginine / Q000008:administration & dosage; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010865:Pilot Projects; D000074262:Rapeseed Oil; D020123:Sirolimus / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology
D000305:Adrenal Cortex Hormones; D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D005229:Fatty Acids, Monounsaturated; D007166:Immunosuppressive Agents; D000074262:Rapeseed Oil; D016572:Cyclosporine; D001120:Arginine; D009173:Mycophenolic Acid; D020123:Sirolimus