T Agishi

Long-term results of ABO-incompatible living kidney transplantation: a single-center experience.

Background. Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT. Methods. Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1<O, 23 patients; B→O, 19 patients; A1B→A1, 7 patients; B→A1, 8 patients; A1→B; 4 patients; A1B<B, 4 patients; A1B→O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6±1.1 and 0.76±0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases. Results. Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function.

(Pyridoxalated Hemoglobin)-(Polyoxyethylene) Conjugate Solution as Blood Substitute for Normothermic Whole Body Rinse-Out

In order to investigate a new possibility for artificial blood with oxygen-carrying capability to be applied to other than mere supplementation, normothermic whole body rinse-out in which artificial blood deriving from perfluorochemical emulsion, Fluosol-DA 20% (Green Cross Co., Ltd., Osaka, Japan) or stabilized hemoglobin solution, (pyridoxylated hemoglobin)-(polyoxyethylene) conjugate solution (Ajinomoto Co., Ltd., Tokyo, Japan) were used as rinsing fluid for a blood purification experiment. Replacement either with approximately 150 ml/kg of Fluosol-DA or stabilized hemoglobin solution showed effective removal of digoxin at a reduction rate of 96.3% or 92.2%, respectively. However, when Fluosol-DA was used, a certain amount of perfluorochemical should be retrieved by centrifugation to avoid a possible toxic effect on the reticulo-endothelial system. Even though 3 out of 6, and 3 out of 8 dogs, respectively, survived for a long period after the procedure, the experimental dogs were very susceptible to infection.

Assessment of Viability of Pancreas Transplants From Non–Heart-Beating Cadaver

THE program of combined pancreas–kidney transplantation from non–heart-beating cadaver donors was introduced in 1990 at Tokyo Women’s Medical College. In case of pancreas transplantation, especially from non– heart-beating cadavers, it is extremely important to minimize warm ischemia and assess the viability of pancreas graft. In the present paper, the methods of assessment of the pancreatic graft viability were investigated.

NEO RED CELL AS AN ORGAN PRESERVATION SOLUTION

Neo red cell (NRC) was derived from outdated human red cells. The following experimental work has been done in order to investigate if NRC is valid for organ preservation. Hearts were obtained from male Lewis rat (250-350 g body weight). Heart transplantation was performed as Ono-Lindseys method after 1, 3, 6, 12 and 24 hours simple cold storage. Rats were divided into two groups. Group 1; original NRC as preservation solution, Group 2; modified NRC (NRC suspended with UW solution) as preservation solution. After 1, 3, and 6 hour cold ischemic storage, the transplanted hearts in both groups showed contraction immediately after declamping the aorta and the pulmonary artery. After 12 and 24 hour preservation, the transplanted hearts in group 2 showed contraction. Myocardial ATP levels after 6, 12, 24 hours cold storage compared with 0 hour were 62.3%, 28.3%, 32.8% in group 1 respectively. On the contrary, myocardial ATP levels were 87.2%, 57.6%, 52.2% in group 2 respectively. After 24 hour preservation, pathological change was not remarkable between the two groups. Results of the prolonged preservation time and the myocardial ATP changes suggest that there is a possibility for effective use of NRC not only as blood substitute but also organ preservation solution.

Successful Third Kidney Transplantation With Intensive Immunosuppression in a Highly Sensitized Recipient

HLA sensitization associated with previous kidney transplantation is a major drawback to retransplantation. Recently we successfully performed a third graft using intensive immunosuppression for a highly sensitized recipient. The patient was a 31-year-old man who had previously undergone a living donor graft from his father at our institute in 1999. His kidney graft function had deteriorated due to chronic allograft nephropathy, returning to hemodialysis therapy in 2005. He received a second graft from a deceased donor in another country on August 14, 2006. It rejected on postoperative day 3 possibly due to acute accelerated rejection. He was offered a third kidney from his brother. Panel-reactive antibody (PRA) tested before the third procedure revealed positive class I (88%) and class II (96%) PRAs. Mycophenolate mofetil (MMF) was started 3 weeks before the third transplantation, and preoperative plasmapheresis performed thrice. He underwent the living donor graft on March 9, 2007. Immunosuppression consisted of tacrolimus, MMF, methylprednisolone, and basiliximab. Immediately afterward there was a sudden decrease in allograft blood flow and urine output, implying hyperacute rejection. Following treatment with plasmapheresis and a single dose of rituximab (200 mg), the kidney allograft function recovered, although the PRA at 3 weeks was still positive. Six months posttransplantation, he is well with a creatinine of 0.9 mg/dL. Our protocol may reduce the risk for graft loss in a highly sensitized transplant recipient.

Significant Prolongation of Guinea Pig Heart Contraction Transplanted in Rat After Removal of Anti-Xeno-Antibodies by Whole Body Rinse-out(WBRO) with Hemoglobin Solution

PURPOSEnIn order to investigate effectiveness of removal of the anti-xeno- antibodies in xenotransplantation (xeno Tx), WBRO using pyridoxalated-human hemoglobin-polyethyleneglycol conjugate (PHP solution) was performed prior to transplantation (Tx) of a guinea pig heart in a rat.nnnMATERIALS & METHODnExperiment I. Removal of the immunoglobulins and the anti-guinea pig lymphocytotoxic antibody (ALA) by WBRO. Exchange transfusion with the PHP solution was done in the Tx-expected rats until a hematocrit lowered below 5% (n = 11). Experiment II. Xeno heart Txs. Guinea pig hearts were transplanted into rats without immunosuppressants 1) without (n = 8) or 2) with the WBRO (n = 8).nnnRESULTSnExperiment I. Levels lowered to 14% in IgG, 17% in IgA and 6% in IgM, respectively, to initial values after the WBRO. An ALA titer lowered from 4 X (+) to 1 X (-) after the WBRO. Experiment II. An average heart contraction period was 10.4 +/- 1.8 minutes 1) without the WBRO in contrast to 472.5 +/- 4.8 minutes with the WBRO (p < 0.01).nnnCONCLUSIONnWBRO using PHP solution is effective in removal of the anti-xeno-antibodies and consequent prolongation of survival of the xenograft.

Long Term Liver Preservation Using Artificial Blood Substitutes

Twenty-four hour hypothermic perfusion preservation of the liver was aimed using an artificial blood substitutes. A canine liver was harvested and preserved using originally designed perfusates. In group 1, Perfluorotributylamine solution (Oxypherol solution) was used. In group 2, (Pyridoxylated hemoglobin)-(Polyoxyethylene) conjugate solution (Stabilized Hemoglobin, PHP-1). In group 3 and in group 4, modified Stabilized hemoglobin, PHP-3 and PHP-4 was used. After the preservation, each liver was transplanted orthotopically. Postoperative graft function was estimated the following parameter, such as bile excretion, consciousness level, activated clotting time, and survival rate. In group 1 and group 2, improvement of such factors were not fully observed. On the contrary, in group 3 and 4, complete recovery of the function was seen and in group 4, longer survival was obtained. PHP solution was considered suitable perfusate for liver preservation.

Characterization of bovine cells for xenotransplantation

From the Tokyo Women’s Medical University, Kidney Center, Department of Surgery and Central Research Institute for Feed and Livestock, ZEN-NOH, Tokyo, Japan. Supported by Research funds of Ota Medical Research Institute and New Medical Research Foundation. Address reprint requests to Dr T. Muarakami, Tokyo Women’s Medical University, Kidney Center, Department of Surgery, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Long-Term Results of ABO-Incompatible Living Kidney Transplantation. A Single-Center Experience

BACKGROUNDnDespite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT.nnnMETHODSnSixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases.nnnRESULTSnPatient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa

Evaluation of a Pyridoxylated Hemoglobin Polyoxyethylene Conjugate Solution as a Perfusate for Small Intestine Preservation

A new type of artificial blood, pyridoxylated hemoglobin-polyoxyethylene conjugate (PHP) solution, (developed by PHP research group of the department of health and welfare of Japan, and produced by Ajinomoto Co., Inc. Tokyo) as an oxygen-carrying component, has been recently devised using hemoglobin obtained from hemolyzed human erythrocytes. Recently, the studies using this solution as a preservation solution were performed in some instances. To examine the mechanism of improved viability using this solution as a preservation solution, we developed a model of orthotopic small intestine transplantation (OIT) in the rat. As a baseline study, we compared parameters of viability of the grafts preserved in Collins and UW solution to those preserved in PHP solution including a survival rate, a serum level total protein and albumin, and a change in body weight after transplantation. In our study, the simple hypothermia storage together with intestinal perfusion preservation with PHP solution was performed. Animals were divided into 6, 12, and 24 hr preservation groups. All of the rats survived after 6 hr preservation following transplantation. However, in 12 hr storage, five of six rats in PHP solution preservation survived and recovery in body weight after grafting was better than those with Collins and UW solution. We conclude that the PHP solution is, therefore, considered to possibly be a more suitable perfusate for small intestine preservation than Collins and UW solution.