Hypothermic Machine Perfusion Preservation Is Efficient for Non-Heart-Beating Donor Kidney Transplantation in Japan

Abstract

Background: In Japan, brain-dead donors have been increased by revised Act of Organ Transplantation, however, insufficiency of deceased donors is still serious problem. In kidney transplantation, it is important to use marginal donors such as non-heart-beating donors for solving this problem. Static cold storage (SCS) is the most widely used organ preservation method for deceased donor, and in Japan it is now the only technique for kidney preservation, however, hypothermic machine perfusion (HMP) preservation technique may improve better outcomes than SCS. Because, HMP technology has had a major impact in circumventing ischemic injury in kidney transplantation in western countries. In this presentation, we report efficiency of HMP method for preservation of long ischemic kidney grafts in beagle and a case report of clinical usage to kidney transplantation of non-heat-beating donor in Japan. Methods: Young beagles were used as autonomal HMP transplantation model. After general anesthesia of beagles, left renal artery and vein were made ligation, after 30 min warm ischemia time (WIT) in situ, the left kidney was harvested. Each harvested kidney was assigned to one of two preservation treatment groups; SCS group (storage in University of Wisconsin solution at 2-4°C for 24h, n=5); HMP group (storage on LifePort® (Organ Recovery Systems), a portable hypothermic machine perfusion apparatus, at 4-6°C on pulsatile pressure (30 mmHg) for 24h with KPS-1 solution, n=5). After the storage, wedge biopsies were taken for histological evaluation (HE staining and TUNEL staining). The preserved graft was transplanted to the same beagle in left iliac fossa and removed the other kidney. After the operation, recipient survival and graft qualities (urine output, serum creatinine, sodium and potassium) were checked as the clinical outcomes. Results: All recipients of HMP group survived, however, three recipients of SCS group were dead with uremia. Serum creatinine level of HMP group was under 4mg/dL in all post-operation period and reduced under 1.5mg/dL after 11days of post-operation. The other hand, that of SCS group went up over 5mg/dL and did not reduce under 3mg/dL. In histological findings, HE staining revealed that a little bit interstitial edema was exist with HMP groups, and remarkable interstitial edema and vaculolation were exist with SCS group. TUNEL staining showed that apoptosis cells were scattered in tubular epithelium of only SCS group. [Case report] First clinical case of LifePort® preservation in Japan is a 39-year-old woman who had accepted hemodialysis with unexplained renal failure. She underwent deceased donor renal transplantation with preserved kidney with LifePort®. She had immediate urine and discharged hospital without any complications. Withdrawal of hemodialysis was achieved, and the allograft renal function presents well and stable after one-year post-operation. Discussions and conclusions: In this experiment, we indicate that HMP would be better for long term WIT kidney model compared with SCS method in beagles. We experienced first clinical case of deceased donor (non-heart-beating donor) kidney transplantation with LifePort® preserved graft in Japan. It suggests that with marginal donor that is non-heart-beating and is with long agony, HMP should be paid more tribute to than SCS technique.