Prevention of acute rejection with antithymocyte globulin, avoiding corticosteroids, and delaying cyclosporin after renal transplantation.
BACKGROUND
Despite their well-known side-effects, corticosteroids (Cs) are currently used after kidney transplantation. Avoidance of Cs may improve patient quality of life and eventual long-term survival. We report on a regimen using antithymocyte globulin (ATG) and mycophenolate mofetil (MMF) for induction, and cyclosporin (CsA) plus MMF for maintenance treatment of recipients of primary kidney transplantation.


METHODS
We studied 11 consecutive, non-sensitized renal transplant patients (nine cadaver and two living donors). Initial immunosuppression consisted of ATG (1.5 mg/kg/day, i.v.) given for 10 days and MMF (1.0 g/b.i.d.). CsA (8 mg/kg, in two divided doses) was started on post-operative day 11. Cs were only allowed in the case of MMF discontinuation, for the treatment of acute rejection, and in the event of recurrence of the primary glomerulonephritis.


RESULTS
All patients completed the entire 10-day ATG course. Main side-effects included fever (>38 degrees C) and serum sickness, observed in 73 and 27% of the patients respectively. The incidence of acute rejection was 27% (three of 11 patients). In two patients with acute rejection, serum sickness was concomitantly diagnosed and renal histology was partially compatible with immune-complex disease. The remaining patient had two episodes of low-grade rejection. All rejection episodes were rapidly reversed. Two patients (18%) were treated with ganciclovir for cytomegalovirus (CMV) infection. Two patients (18%) are currently receiving Cs for recurrence of the native glomerulonephritis and two rejection episodes respectively. All patients are currently alive with functioning kidneys (average follow-up of 8.4 months; average creatinine level of 128 micromol/l).


CONCLUSIONS
This pilot study suggests that ATG induction in combination with MMF and delayed introduction of CsA, in the absence of Cs, is not well tolerated in recipients of kidney transplants. An earlier introduction of calcineurin inhibitors and/or a shorter course of ATG may reduce the incidence of fever and serum sickness secondary to ATG.
Cantarovich
D
D
Department of Nephrology and Clinical Immunology, Institut de Transplantation et de Recherche en Transplantation (ITERT), Nantes, France.
Giral-Classe
M
M
Hourmant
M
M
Dantal
J
J
Blancho
G
G
Lerat
L
L
Moreau
A
A
Soulillou
J P
JP
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001706:Biopsy; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000209:etiology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control* / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010865:Pilot Projects; D011183:Postoperative Complications
D000305:Adrenal Cortex Hormones; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid