Simultaneous Pancreas and Kidney Transplantation from ABO-Incompatible Living Donors in Japan. - Six Consecutive Clinical Trials in a Single Institution

Takashi Kenmochi¹, Taihei Ito T¹, Takehide Asano T², Naotake Akutsu², Kiyotaka Hoshinaga³, Hisahiro Matsubara⁴

1. Department of Organ Transplant Surgery, Fujita Health University, School of Medicine, Aichi, Japan
2. Department of Surgery, Chiba-East National Hospital, NHO, Chiba, Japan,
3. Department of Urology, Fujita Health University, School of Medicine, Aichi, Japan
4. Department of Academic Surgery, Chiba University, School of Medicine, Chiba, Japan

As an option for the treatment of type 1 diabetic patients with an end-stage renal disease (ESRD) because of a limited use of brain dead donors in our country, we have introduced simultaneous pancreas and kidney transplantation (LDSPK) from ABO-incompatible living donor and six cases were, so far, performed. In this paper, we report the technique and the outcome of our six consecutive clinical trials.

Patients and methods: Six type 1 diabetic patients with ESRD (Ages were 31.0+5.0 years ranging from 25 to 40 years, 2 males/4 females) underwent LDSPKs from ABO-incompatible donors. Their pretransplant serum C-peptide levels (CPR) were <0.03 ng/ml and hypoglycemic unawareness frequently occurred. Donors were 5 mothers and 1 brother. Ages were 54.5+7.2 years and ABO blood types were incompatible (A₁→O in 3 cases, A₁B→A₁, A₁B→ B, B→O　in one case, respectively). Desensitization and immunosuppression were achieved by a splenectomy (3 cases) or rituximab (3 cases), three times of double filtrated plasmapheresis, plasma exchange and quadruple therapy by tacrolimus, MMF, predonisolone, and basiliximab. In the donor operation, left nephrectomy and distal pancreatectomy were performed under hand-assisted laparoscopic surgery. In the recipient, pancreatic graft was transplanted into the right iliac fossa using a bladder drainage technique and the kidney graft into the left iliac fossa.

Results: No donors showed any complications, including pancreatic fistula, diabetes or renal dysfunction for more than five years. The pancreas and kidney grafts functioned immediately after transplantation in all recipients, thus resulting in a rapid decrease of serum creatinine levels and insulin independency. Five-year patient survival is 100%. Five-year graft survivals are 100% in the pancreas and 83.3% in the kidney. Although acute cellular rejection occurred in the first two recipients, no antibody-mediated rejection was observed in any of the recipients. In mmunohistochemical study, both A- and B-antigens were distributed in the endothelial cells of artery and glomerular capillary in the kidney grafts. Although distal tubules expressed A- and B- antigens, proximal tubules did not express them. While, both A- and B-antigens distributed in exocrine tissue and pancreatic duct in addition to the endothelial cells of artery and vein. Islet cells, however, did not express both A- and B-antigens. All recipients maintained insulin independency with positive serum CPR levels (1.0-3.5ng/ml) and normal HbA1c (4.8-5.8%) for over five years. All recipients showed normal endocrine function as evaluated by HbA1c levels, HOMA-b, HOMA-R, insulinogenic index and a 75 g-oral glucose tolerance test. Quality of life of the recipients evaluated with Short Form 36 showed the drastic improvement after LDSPK. Also, quality of life of the donors was maintained over 50, that is the Japanese standard level. However, the first recipient developed kidney graft failure at 2 years PO because of severe dehydration associated with uncontrolled diarrhea.

Conclusions: Our clinical data clearly demonstrated that ABO-incompatible pancreatic grafts survived as well as kidney grafts even from A1 or B incompatible donors. As a result, LDSPK from an ABO-incompatible living donor is therefore considered to be an effective treatment for type 1 diabetic patients with ESRD.