The use of an anti-CD25 monoclonal antibody and mycophenolate mofetil enables the use of a low-dose tacrolimus and early withdrawal of steroids in renal transplant recipients.
BACKGROUND
Reducing calcineurin-inhibitor-induced nephrotoxicity and simultaneously avoiding long-term steroid related side-effects is a desirable goal in renal transplantation. We examined the hypothesis that using anti-CD25 monoclonal antibody induction and mycophenolate mofetil (MMF) would allow the lowering of target pre-dose blood concentrations of tacrolimus immediately after transplantation and subsequently stopping steroids at 5 months.


METHODS
Eighty-two kidney recipients were enrolled in a single-center study comparing two tacrolimus-based protocols. Group I (n = 41) patients received a standard-dose tacrolimus (blood concentration 10-15 ng/mL) with MMF and a standard dose corticosteroid. Group II (n = 41) patients were treated with a low-dose tacrolimus (blood concentration 5-10 ng/mL) and MMF, a low-dose corticosteroid (stopped after 5 months) and induction with daclizumab.


RESULTS
Patient (95.1 versus 100%) and graft survival (92.6 versus 97.5%) at 1 yr were not different between groups. Patients of group II experienced significantly less acute rejections than group I (17.1 versus 41.4% p = 0.03). Delayed graft function occurred less often in group II (5 versus 12% p = 0.43). Graft function at 1 yr was significantly better in group II (serum creatinine 1.49 versus 1.69 mg/dL and creatinine clearance 59.6 versus 49 mL/min; p < 0.05). Corticosteroids could be stopped after 5 months in 82.9% of group II patients.


CONCLUSIONS
A regimen consisting of anti-CD25 monoclonal antibody induction and MMF allows the safe and efficient use of low-target pre-dose trough concentrations of tacrolimus and enables the early discontinuation of steroids. Preliminary results indicate a better 1-yr graft function compared to a normal-dose tacrolimus regimen.
Kuypers
D R J
DR
Department of Nephrology, University Hospitals Leuven, Leuven, Belgium. dirk.kuypers@uz.kuleuven.ac.be
Evenepoel
P
P
Maes
B
B
Coosemans
W
W
Pirenne
J
J
Vanrenterghem
Y
Y
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D010865:Pilot Projects; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D016559:Tacrolimus / Q000008:administration & dosage* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008775:Methylprednisolone