Use of skin grafting to demonstrate tolerance before kidney transplantation without immunosuppression in the recipient of a previous bone marrow transplant.

Chronic renal insufficiency is a rare complication of bone marrow transplantation (BMT), occurring in 0.8% to 9.5% (1, 2) of patients and may be of sufficient severity to require renal replacement therapy. When BMT has been used as treatment for hematologic malignancy, an immune-mediated graft-versus-leukemia effect may be needed to maintain remission because systemic immunosuppression after cadaveric renal transplantation could cause risk of relapse of leukemia. The ideal kidney donor would be the same individual who donated the bone marrow. The recipient’s immune system could be identical or chimeric with that of the donor. It is difficult to be certain that 100% of the recipient immune system has been eradicated, and a small residual could proliferate to reject a donated kidney. Ethically, to submit a live donor to nephrectomy, a high level of assurance of success is needed. We present a case in which tolerance using a skin graft was demonstrated before successful kidney transplantation without immunosuppression in a BMT recipient. A 64-year-old male was referred for assessment of chronic renal insufficiency in January 2001. Four years previously, he had had chronic myeloid leukemia (CML) treated successfully with an allogenic BMT from his human leukocyte antigen (HLA)-identical (HLA-A, B, and DR only tested) sister. Two episodes of graft-versus-host-disease (GvHD) were treated with short courses of steroids and cyclosporine. In April 2001, relapse of CML was diagnosed on the basis of break-point cluster region Ableson leukemia transcripts found by polymerase chain reaction in peripheral blood and by 11 of 200 cells being of recipient (male) origin on bonemarrow examination. The relapse was successfully treated with donor lymphocyte infusion. PreBMT he had long-standing hypertension controlled by a single agent and normal kidney function. At referral, his serum creatinine had been raised for more than 24 months. An ultrasound examination revealed an absent left kidney and 9 cm right kidney. Renal insufficiency was progressive, and he was begun on peritoneal dialysis. The sister who had donated the bone marrow offered to donate a kidney. A full-thickness skin graft from the sister was performed in July 2002. One month after skin grafting, the graft had been accepted with no clinical or histologic evidence of rejection (Fig. 1). Kidney transplantation then took place without any induction or maintenance immunosuppression. Two years posttransplant, the patient remains well without episodes of transplant kidney rejection or recurrence of leukemia, with a serum creatinine of 1 mg/dL (89 mol/L). In a patient with prior documented GvHD, skin grafting provided a simple, practical, in vivo immunologic challenge to reassure us that live-donor renal allografting could be successful without immunosuppression. To our knowledge, there have been only two similar cases reported previously (3, 4). Even though the paradigm of solid-organ transplantation from the same donor in previous BMT recipients is not applicable to the vast majority of organ recipients, it offers a unique opportunity to realize the benefits of tolerance and avoid deleterious effects of immunosuppressive medication, including the risk of relapse of the primary hematologic malignancy.