Pancreas Transplantation After Combined Heart-Kidney Transplantation

We describe the first reported case of pancreas transplantation after combined heart-kidney transplantation for type 1 diabetes mellitus (DM1) complicated by end-stage cardiac and renal failure. The patient is a 32-year-old single mother. She had a 20-year history of poorly controlled DM1 (hemoglobin A1c=14.4%, C-peptide negative) complicated by retinopathy, polyneuropathy, gastroparesis, peripheral vascular disease, and nephropathy. She had ischemic cardiomyopathy (class IV angina), for which surgical therapy with coronary artery bypass graft and percutaneous stentings of occluded bypass grafts failed. She progressed to end-stage ischemic cardiomyopathy (ejection fraction=35%), requiring multiple hospitalizations for acute heart failure during the past 3 months. Her renal function also deteriorated to a glomerular filtration rate of 28 mL/min/1.73 m2. Therefore, she had evidence of triple organ failure. Because of poor renal function, she was not eligible for a heart transplant alone. Therefore, she first underwent combined heart-kidney transplantation (Table 1). Postoperatively, she remained hospitalized for 1 month because of Clostridium difficile colitis and wound infection. Follow-up heart biopsies were grade 0R/1R, not requiring additional immunosuppression, and serum creatinine remained stable (0.6–0.8 mg/dL).TABLE 1: Donor characteristics and immunosuppressionBecause of poor quality of life from DM1 and its risk to endanger the stable heart-kidney allografts, she subsequently underwent pancreas transplantation with portal venous and enteric exocrine drainage 6 months later (Table 1). Insulin was discontinued on postoperative day 2, and glycemia remained stable thereafter. She was discharged on day 5 and remained without clinical evidence of rejection in all three allografts at 14 months follow-up. She did not require any further hospitalizations, and her quality of life greatly improved. She remains in excellent condition, normoglycemic without exogenous insulin (hemoglobin A1c=5.5%) and has normal serum creatinine and cardiac function, 20 months after heart-kidney and 14 months after pancreas transplantation. This is the first reported case of pancreas transplantation after combined heart-kidney transplantation performed for the rare triad of DM1, end-stage cardiac failure, and end-stage renal failure. The presence of this triad has been traditionally considered a contraindication for heart, kidney, or pancreas transplantation (1). Only one previous reported case of simultaneous heart-kidney-pancreas transplantation has successfully challenged this dogma (1). We decided to perform a combined heart-kidney transplantation followed by subsequent pancreas transplantation instead of the triple organ transplantation for the following reasons. First, our patient absolutely needed heart and kidney transplantation for survival. Although her DM1 was poorly controlled, it was not immediately endangering her life, and we considered delaying pancreas transplantation to minimize risks of early pancreas-related complications threatening graft and patient survival. Simultaneous pancreas transplantation could, in fact, put all grafts at risk from prolonged operative time and reperfusion injury, particularly when heart transplantation by itself already disturbs hemodynamic stability (2). This would increase the chance of pancreas graft failure within the first year and potentially decrease patient survival (3). Also, rate of relaparotomy because of graft thrombosis, duodenal stump leak, severe pancreatitis, or intraabdominal abscess after pancreas transplantation has been reported to be as high as 32% (4). Moreover, starting with a combined heart-kidney transplantation is likely safer because it has been documented to be of equivalent success as solitary heart transplantation in a multicenter trial (5). We believe the previous advantages outweigh the disadvantages of repeat surgical procedure, repeat induction of immunosuppression, and repeat exposure to alloantigens. Despite shared human leukocyte antigen mismatches between the heart-kidney and the pancreas donors, our patient did not experience any episodes of clinical rejection in any of her three allografts at 14 months follow-up. A possible explanation would be a state of tolerance to these antigens. Certain characteristics of multiple or sequential organ transplantations may also play a role in reduction of immunologic risk. It has been theorized that a large burden of transplanted tissue may lead to a state of anergy (6), strength of immune response could be diverted among multiple organs (6), and patients with previous stable grafts are immunologically favored (7). In conclusion, pancreas transplantation after combined heart-kidney transplantation is a viable option for selected patients with severe DM1 complicated by end-stage cardiac and renal failure. Although additional cases need to be reported and long-term immunologic outcomes remain unknown, this approach might confer an advantage to simultaneous heart-kidney-pancreas transplantation with respect to safety and early severe complications and potentially offer a further advantage compared with heart-kidney transplantation alone, with respect to improved diabetic control and quality of life. Staged pancreas transplantation should, however, only be attempted once the combined heart-kidney allografts are stable, and all organs should be followed up individually for evidence of rejection. Minh-Tri J.P. Nguyen1 Nadia Giannetti2 Marcelo Cantarovich2 Renzo Cecere1 Prosanto Chaudhury1 Steven Paraskevas1 1 Multi-Organ Transplant Program Department of Surgery McGill University Health Centre Montreal, QC, Canada 2 Multi-Organ Transplant Program Department of Medicine McGill University Health Centre Montreal, QC, Canada

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