Acute rejection of renal allografts: Mechanistic insights and therapeutic options

Abstract

Case presentation A 44-year-old white woman was admitted to The New York Hospital for a living-donor renal transplant from her husband. One and one-half years prior to admission for transplantation, she was found to have advanced renal failure; renal biopsy at that time revealed crescentic glomerulonephritis. The patient was started on maintenance hemodialysis one year prior to admission for transplantation. Pre-transplantation serology studies were negative for hepatitis B and hepatitis C virus. The recipient and donor were cytomegalovirus positive. The HLA type of the recipient was A2, All, B51, B52, and DR2 and 4; the HLA type of the donor was A2, A24, B51, B62, and DR1 and 5. The recipient was preconditioned with a regimen of donor-specific transfusions and cyclosporine. Donor-specific T- and B-cell crossmatches, including the flow cytometry crossmatch, were negative, and the patient underwent renal transplantation from her spousal donor. The immunosuppressive regimen comprised cyclosporine (10 mg/kg/day, in two divided doses), azathioprine, and corticosteroids. The renal transplant functioned immediately. The patient's serum creatinine decreased from a pretransplant value of 14.6 mg/dl to 1.0 mg/dl by the second postoperative day and remained at that level until day 5 post transplantation. On postoperative day 6, her serum creatinine increased to 2.8 mg/dl. A renal scan showed decreased uptake, and the renal sonogram did not reveal an obstruction. A diagnosis of acute rejection was made, and the patient received a course of steroid pulse therapy (250mg intravenously, twice daily for 3 days). Her serum creatinine level peaked at 5.4 mg/dl on day 9 post transplantation. The patient responded to pulse therapy, and the serum creatinine level declined until day 15. A percutaneous core needle biopsy disclosed changes consistent with acute cellular rejection. The renal biopsy material was processed for mRNA phenotyping by reverse-transcriptase polymerase chain reaction (RT-PCR). Following a second course of steroid pulse therapy, the patient's serum creatinine declined to 1.5 mg/dl, and she was discharged from the hospital on day 20 post transplantation. Her medications at that time included the following immunosuppressants: cyclosporine, 250mg orally, twice daily; azathioprine, 150mg orally each day; and prednisone, 30mg orally twice daily. Her whole-blood cyclosporine level (determined with the monoclonal antibody specific for the parent compound) ranged from 90 ng/ml to 360 ng/ml during the transplant hospitalization. The patient is being followed in the transplant clinic, and her serum creatinine values were 1.1, 1.3, 1.5 and 1.6 mg/dl four, three, two, and one year ago, respectively.