A single center's clinical experience with quadruple immunosuppression including ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas-kidney transplants.
Acute rejection remains a major problem in simultaneous pancreas-kidney (SPK) transplant and occurs in 60-100% of the cases. With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving antithymocyte globulin (ATG) or Basiliximab induction therapy and cyclosporine Neoral (CyA), MMF, steroid basis immunosuppression. Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean +/- standard deviation (SD) age of 42 +/- 6 yr. Of these, 14 patients were treated with anti-thymocyte globulin (ATG) Fresenius (rabbit) 3-5 mg/kg for 6 +/- 2 d, cyclosporine Neoral (CyA) (trough levels 350-400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect, Novartis 20 mg on d 0 and d 4 post-transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean +/- SD cold ischemia time (CIT) of the organs was 10.1 +/- 2.4 h for the pancreas and 10.5 +/- 2.6 h for the kidney.


RESULTS
Biopsy-proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6-d course of anti-CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA1C) of 5.1 +/- 0.7%, and serum creatinine with a mean of 1.24 +/- 0.24 mg/dL in a mean follow-up period of 17 +/- 15 months (median 12, range 2 37).


CONCLUSIONS
Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas-kidney transplant (PKT) with a marked reduction in the incidence of rejection.
Hesse
U J
UJ
Department of Surgery, Ghent University Hospital, Belgium. uwe.hesse@rug.ac.be
Troisi
R
R
Jacobs
B
B
Van Vlem
B
B
de Hemptinne
B
B
Van Holder
R
R
Vermassen
F
F
De Roose
J
J
Lameire
N
N
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D000077552:Basiliximab; D016572:Cyclosporine / Q000627:therapeutic use*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D005916:Globulins / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016035:Pancreas Transplantation; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D000935:Antifungal Agents; D005229:Fatty Acids, Monounsaturated; D005916:Globulins; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; C053534:fumifungin; D016572:Cyclosporine; D000077552:Basiliximab; D009173:Mycophenolic Acid