Successful ABO Incompatible Kidney Transplant After an Isolated Intestinal Transplant

Abstract

To our knowledge, we herein report the first case in the literature of a living unrelated ABO incompatible (ABOi) renal transplantation after successful isolated small bowel and colon transplantation. This case illustrates several interesting immunologic findings. The patient is a 50-year-old woman with a history of hypertension and cholecystectomy who suffered with complicated endometriosis, which lead to multiple intestinal resections for recurrent obstruction and enterocutaneous fistulae. These ultimately led to short gut syndrome and total parenteral nutrition dependence for 5 years. The patient underwent an ABO identical isolated intestinal transplant (small bowel and right colon) with systemic venous drainage and basiliximab and steroid induction. Posttransplant maintenance included tacrolimus, sirolimus, and prednisone. No rejection was encountered, parenteral nutrition was discontinued, and her ileostomy was reversed 18 months later. Because of poor wound healing and wound infection, sirolimus was discontinued thereafter. One year after small bowel transplantation, the patient experienced progressive renal insufficiency presumed because of tacrolimus toxicity. Despite diuretic therapy, volume management ultimately led to hemodialysis 16 months after transplant. Her only potential live kidney donor was ABOi; the patient was blood group O; and her donor was blood group A. She subsequently underwent an ABOi renal transplant 24 months after her intestinal transplant. The desensitization protocol consisted of pretransplant and posttransplant tacrolimus and mycophenolate mofetil with four preoperative and two postoperative rounds of plasmapheresis and intravenous cytomegalovirus immune globulin. Induction therapy also included 1.5 mg/kg rabbit antithymocyte globulin intraoperatively and on the first 4 postoperative days along with methylprednisolone. Her baseline anti-A antibody titer was 1:64. After plasmapheresis, it decreased to 1:8 below the threshold of 1:32, necessary for successful ABOi renal transplantation (1). It is now 46 months after intestinal transplant and 26 months after her kidney transplant. She continues on a low fat diet with no nutritional support. In addition, she has a good kidney function and a serum creatinine level of 1.8. She is maintained on tacrolimus, mycophenolate mofetil, and prednisone for immunosuppression. The patient has had no evidence of rejection of graft or opportunistic infection. DISCUSSION Intestinal transplantation has improved in the past decade, achieving 1-year patient and graft survival rates in excess of 90% at several centers (2). It has been associated with a 30% to 40% risk of rejection in the first 3 months (3). Ojo et al. (4) report rates of renal failure as high as 21.3% in recipients of intestinal transplants, likely related to aggressive immunosuppression protocols. In this case, we successfully performed an isolated intestinal transplant with an excellent functional outcome using an aggressive immunosuppressive protocol including rabbit antithymocyte globulin induction and maintenance tacrolimus, sirolimus, and prednisone. Eventually the patient developed chronic renal failure, and we followed up this with an ABOi living donor kidney transplant. Despite the exposure to a second set of non-self-human leukocyte antigens and crossing the ABO barrier, there was no episode of rejection of either allograft. We hypothesize that her previous immunosuppression and our desensitization protocol would decrease the likelihood of such an occurrence. At our center, we use sirolimus as a part of our strategy for maintenance immunosuppression for intestinal transplantation, because this has been shown to be of benefit in combating acute rejection (5). She did not have evidence of rejection but did develop a wound infection and poor wound healing necessitating discontinuation of sirolimus. After 1 year, the patient ultimately developed progressive chronic renal failure and required hemodialysis. We believed that this occurred because of tacrolimus toxicity and recurrent dehydration because of high ileostomy output. At her kidney transplantation evaluation, we considered both deceased donor and living donor; ABOi or entering her into a paired kidney donor exchange. Because of a long expected wait time for a deceased donor organ, we opted for a living donor. Her only living donor was ABOi. The patient had no donor-specific antibody and a low ABOi titer to her donor. Such a donor recipient phenotype (O recipient and A donor) have less than 20% chance of a match in a paired kidney donation pool with long projected waiting times (6). Thus, we believed that an ABOi transplant was achievable in a short period of time with less morbidity on hemodialysis. The current shortage of deceased donor kidneys necessitate the use of all strategies to increase the donor pool for patients with end-stage renal disease. This case demonstrates the effective use of ABOi kidney transplantation for end-stage renal disease after intestinal transplantation with the absence of both rejection and opportunistic infection. Lee S. Cummings1 Jason S. Hawksworth1 Juan-Francisco Guerra1 Chirag S. Desai2 Raffaele Girlanda1 Cal S. Matsumoto1 Thomas M. Fishbein1 Lynt B. Johnson3 Joseph K. Melancon1 1Division of Transplantation and Hepatobiliary Surgery Georgetown University Hospital WA 2University of Arizona College of Medicine Tucson, AZ 3Department of Surgery Georgetown University Hospital WA