Tetsuzo Agishi

Anti-AB titer changes in patients with ABO incompatibility after living related kidney transplantations: survey of 101 cases to determine whether splenectomies are necessary for successful transplantation.

Background. A shortage of organ donors for transplantation has become a serious problem throughout the world. To overcome this problem, transplantations across ABO blood barriers have been performed with some success. In general, however, the graft survival rate for transplantation with ABO incompatibility is lower than that of transplantation with ABO compatibility. Unfortunately, the mechanism by which isohemagglutinins might injure an ABO-incompatible graft remains uncertain. Here, the pre- and posttransplantation anti-AB titers in patients who received transplants from ABO-incompatible living donors are reviewed and the pathological findings are compared. Methods One hundred and one patients underwent ABO-incompatible living related kidney transplantation (i-LKT) between January 1989 and October 1999 at our hospital. Plasmapheresis and immunoadsorption were performed in all of the i-LKT patients before the transplantation to remove anti-AB antibodies. A splenectomy was also performed during the operation, followed by the local irradiation of the graft with a dose of 150 rad. The anti-AB titers and pathological findings for 93 i-LKT patients, excluding 8 patients who died, were then examined. Results Immediately after the i-LKT, the anti-AB titer dropped rapidly to below 1:4 in all 93 cases. Seventy of patients (70/93, 75%) showed no elevation in their anti-AB titer during their follow-up. However, the remaining 23 patients (23/93, 25%) showed a significant elevation of their anti-AB titer to over 1:16. Sixteen of these patients (16/93, 17%) exhibited an anti-AB titer of over 1:32. Out of these 16 patients, 11 patients (11/16, 69%) lost their grafts. The anti-AB titer in the remaining five patients (5/16, 31%) spontaneously decreased without any special treatment. Seven patients (7/93, 8%) exhibited an elevated titer of 1:16. Out of these patients, only one patient (1/7, 14%) lost his graft. The elevated titers in the remaining six patients (6/7, 86%) eventually decreased. The graft function improved in patients whose elevated anti-AB titers eventually decreased. Control patients (ABO-compatible kidney transplant patients) showed a normal elevation of their titer values compared with preoperative titers. Pathological findings showed severe humoral rejections in all cases with high anti-AB titers that lost grafts. Humoral rejection was also detected in most of the patients whose anti-AB titer was elevated to over 1:16 after the transplantation, but excellent renal function was resumed once the titers decreased to below 1:4. Conclusions In 23 out of 93 i-LKT patients (25%), the anti-AB titers were significantly elevated after the splenectomy. In view of other reports of i-LKT without splenectomy, we feel that a splenectomy in i-LKT patients might be unnecessary. Pathological evidence suggests that the decrease in the anti-AB titer after transplantation might be the net result of plasmapheresis before the operation and the adsorption of antibodies to the endothelium of the transplanted organ after the operation, neither of which is influenced by a splenectomy.

Analysis of postoperative liver function of donors in living-related liver transplantation: comparison of the type of donor hepatectomy.

BACKGROUND There is a potentially significant risk to the donor in living-related liver transplantation. METHODS We analyzed surgical risk and stress to 35 donors in living-related liver transplantation with special reference to the types of donor hepatectomy. Donor surgery was performed in one of three ways: (1) lateral segmentectomy without ligation of the middle hepatic vein (MHV) in the remnant liver (group 1, n=21); (2) lateral segmentectomy with ligation of MHV in the remnant liver (group 2, n=6); and (3) left lobectomy with MHV (group 3, n=8). RESULTS No critical complications were observed in any group. The postoperative enzyme levels in group 2 were significantly higher than those in groups 1 and 3 (P<0.01). Although blood loss was covered by autologous blood transfusion in the first six cases, no banked blood was transfused in any of the cases. Surgical duration was significantly longer and blood loss was significantly greater in group 3 than in group 1 (P<0.05). Follow-up computed tomography showed atrophic changes in segment IV in groups 1 and 2. No remarkable changes were seen in segments V or VIII in any of the three groups. CONCLUSION Regardless of the donor hepatectomy procedure, serious complications did nor occur after surgery. Although it should be noted that the type of donor hepatectomy affects postoperative donor liver function, left lateral segmentectomy with ligation of MHV in the remnant liver is a useful method for obtaining liver grafts from living-related donors who have unusual anatomic variations of the hepatic veins.

Effects of internal filtration on the solute removal efficiency of a dialyzer.

To improve solute removal efficiency, several types of dialyzers with enhanced internal filtration were introduced for clinical application. In these dialyzers, enhanced internal filtration increased convective transport of the solute, in addition to diffusive transport. In this study, the effects of internal filtration on solute removal efficiency were examined by both analytic and experimental studies. Internal filtration is affected by blood (QB) and dialysate (QD) flow rates; the patient’s hematocrit and plasma level of total protein; and the effective length (Leff), inner diameter (D), and density ratio (DR) of the hollow fibers. An analytic model was introduced for the estimation of the changes in mass and momentum along the dialyzer. It clarified the effects of these parameters on maximum internal filtration flow rate (QIF) and clearance (K) of urea (60 daltons), vitamin B12 (1,355), and myoglobin (17,000). As a result of the analytic study, QIF was increased, resulting in a smaller D, a longer Leff, and a larger DR value. Several types of dialyzers with the same cellulose triacetate membrane, produced by Toyobo Co, Ltd., Ohtsu, Japan, and Nissho Corporation, Kusatsu, Japan, were used for the experimental study. An in vitro evaluation using myoglobin solution showed the same trends as found in the analytic study. For example, a dialyzer with 150 &mgr;m of D has a 72.0 ml/min myoglobin K value, much higher than that of 53.7 ml/min for a dialyzer with 200 &mgr;m of D under constant QB (300 ml/min) and DR (50%) values. Development of a dialyzer with enhanced internal filtration, however, should take the patient’s safety into account, and hemolysis and endotoxin invasion from the dialysate to the patient should be avoided.

Clinical application of vascular closure staple clips for blood access surgery

We investigated the usefulness of nonpenetrating titanium vascular closure staple (VCS) clips developed for anastomosis of peripheral blood vessels. VCS clip applier systems (Autosuture; United States Surgical Corporation, Norwalk, CT) were used for 10 patients on hemodialysis who needed peripheral vascular anastomoses for blood access. Two arteriovenous (AV) fistulas, one closure of a fistula with reconstruction of the radial artery, six vascular graft implantations, and one vascular graft closure were performed. Medium clips were used for AV fistulas and large clips for vascular graft implantation. It took 12 min, on average, for vascular access graft anastomoses and 8.5 min, on average, for the AV fistulas. In two patients, bleeding from the anastomosed site occurred after declamping and additional sutures were required; however, neither hematoma nor wound infection occurred at 9 to 12 months after surgery. In one patient, stenosis of the graft-venous junction was found and was successfully treated by percutaneous transluminal angioplasty. The VCS clip applier is easy to manipulate, is as safe as hand-suture methods, and has time saving potential. We conclude that these VCS clips are useful for vascular anastomoses of blood access.

Solute removal characteristics of continuous recirculating peritoneal dialysis in experimental and clinical studies.

Continuous recirculating peritoneal dialysis (CRPD) was introduced to enhance solute removal efficiency in conventional peritoneal dialysis (PD) therapies such as continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a portion of the dwell dialysate in the patients peritoneal cavity is drained through a double-lumen catheter and purified by an extracorporeal dialyzer. In this study, solute removal characteristics and safety of CRPD are examined in ex vivo and clinical studies. Recirculation dialysis experiments using nine dogs (13.6 +/- 2.5 kg of body weight) were carried out for 240 min in the ex vivo study, whereas another seven dogs (12.1 +/- 2.8 kg) received conventional peritoneal dialysis (CPD) (120 min dwelling x 2) and six additional dogs (11.9 +/- 2.7 kg) received a Tidal PD (20 min dwelling x 12; 50% of tidal volume ratio) as controls. The ex vivo study revealed that CRPD has a higher efficiency for solute removal than CPD and is equivalent to Tidal PD. In the BUN reduction rate, the 19.4 +/- 5.5% in 240 min CRPD (n = 9) was significantly higher (p < 0.05) than the 3.5 +/- 3.6% in 240 min CPD (n = 7) and equivalent to the 17.3 +/- 4.7% in 240 min Tidal PD (n = 6). Continuous recirculating peritoneal dialysis maintained a low UN level in the peritoneal cavity due to dialysis with an extracorporeal dialyzer. This tendency was also seen in creatinine removal. In the clinical study, CRPD (n = 10) and CPD (n = 5) treatments were used in three renal failure patients. Higher solute removal efficiency was shown in CRPD than in CPD treatments, and the urea peritoneal clearance was 14.1 +/- 4.4 ml/min in CRPD (n = 10), significantly higher (p < 0.05) than the 7.3 +/- 2.1 ml/min in CPD (n = 5). No fibrin formation occurred during CRPD treatments.

First report of a 7-year survey on ABO-incompatible kidney transplantation in Japan

AbstractBackground. As of December 1997, more than 170 000 patients in Japan were receiving hemodialysis, 30% to 50% of whom were waiting for a kidney transplant. However, in contrast to the situation in the United States and Europe, kidney transplantation is uncommon, because of the small number of cadaveric kidneys that are donated. As a result, living-related kidney transplantation is performed in as many patients as possible, even in ABO-incompatible cases. Methods. We statistically analyzed the data for 167 ABO-incompatible living donor kidney transplantations that were carried out between January 1989 and December 1997. Results. The overall patient survival rates at 1, 3, 5, and 7 years after transplantation were 90.2%, 90.2%, 88.0%, and 84.8%, respectively, with respective overall graft survival rates of 79.6%, 76.1%, 66.3%, and 56.5%. Conclusions. ABO-incompatible living kidney transplantation is an effective radical treatment for endstage renal disease (ESRD).

Development of continuous recirculating peritoneal dialysis using a double lumen catheter.

Continuous recirculating peritoneal dialysis (CRPD) was newly introduced to improve solute removal efficiency in conventional dialysis therapies such as hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a part of the dialysate in the peritoneal cavity was drained through a double-lumen catheter and purified by an extracorporeal dialyzer. Urea removal characteristics in CRPD were examined in a canine study. In this study, a recirculation-dialysis experiment using a dog weighing 9.0 kg was carried out under 100 and 200 ml/min of flow for recirculating and delivered dialysates, respectively. An FB-50H (Nipro Medical Industries, Ltd., Osaka, Japan) composed of cellulose diacetate membrane with 0.5 m2 of surface area and Dianeal-1.5 (Baxter Limited Laboratories, Tokyo, Japan) containing urea were used as the extracorporeal dialyzer and dialysate. Urea peritoneal and dialyzer dialysances (DBP and DBD) were 3.05 and 33.3 ml/min by computer simulation using a compartment model for CRPD. This DBP value can be estimated as 20.3 ml/min for a 60 kg human. From this result, time-averaged value for BUN over an 8 hr/day CRPD, combined with three exchanges/day as CAPD is estimated to be 34.3 mg/dl, which is much lower than 45.2 mg/dl for a 12 hr/week HD, or 53.0 mg/dl for conventional CAPD.

Removal of anti-A/B antibodies for successful kidney transplantation between ABO blood type incompatible couples

A growing shortage of cadaveric donors has prompted expansion of the criteria for acceptable living donors. Because of this, ABO-incompatible kidney transplantation has been carried out. To remove anti-A and/or anti-B antibodies, the recipients received one or two sessions of double filtration plasmapheresis (DFPP) and three or four sessions of immunoadsorption prior to transplantation until the anti-A IgG/IgM titers and/or anti-B IgG/IgM titers decreased to 1:16 or less. Our immunosuppressive protocol involved treatment with the drugs methylprednisolone, cyclosporine, azathioprine, anti lymphocyte globulin and deoxyspergualin. The patient survival was 98% at 1 month, 98% at 3 months, 94% at 6 months, and 92% at 1-5 years. Graft survival was 92% at 1 month, 88% at 3 months, 85% at 6 months, 81% at 1 year, and 76% at 5 years. Both DFPP and/or immunoadsorption eliminated anti-ABO antibodies from ABO-incompatible kidney transplant recipients effectively and safely. The results of the ABO-incompatible kidney transplantation were acceptable and not different from those of ABO-compatible cases.

Bioartificial endocrine pancreas (Bio-AEP) for treatment of diabetes: effect of implantation of Bio-AEP on the pancreas.

Recently, we described a diffusion chamber for a bioartificial endocrine pancreas (Bio-AEP). Pancreatic islet cells in the Bio-AEP device were isolated from the immune system of the host by an artificial barrier, while nutrients, electrolytes, oxygen, and bioactive secretory products were exchanged across this barrier. This experiment was designed to evaluate whether the diffusion chamber could be useful as a Bio-AEP in the treatment of diabetes. Six streptozotocin (STZ)-induced diabetic rats each received a diffusion chamber containing 8 × 106 MIN6 cells as a xenograft Bio-AEP. In the STZ diabetic rats with Bio-AEPs, a return to normoglycemia was observed up to 30 weeks after implantation, without the use of any immunosuppressant. A gradual increase in the body weight of the rats was also observed. In three STZ diabetic rats, diffusion chambers without MIN6 cells were implanted as a sham operation. The fasting blood glucose levels in these three rats remained higher than 600 mg/dl, after implantation, and they lost weight. Thirty-five weeks after implantation, the pancreata were removed from the rats that underwent xenoimplantation, those that had the sham operation, and the normal control rats. In the sham-operated animals, the exocrine tissues of the pancreata were vacuolated and pancreatic B cells were not seen in the islets. In contrast, in the pancreata from the xenoimplantation, the exocrine tissues were normal, and a few pancreatic B cells were seen in the islets. These results indicated that xenoimplantation using the Bio-AEP might retard the progress of diabetes.

Evaluation of blood access dysfunction based on a wavelet transform analysis of shunt murmurs.

We investigated shunt murmurs based on wavelet transform analysis as a new method for assessing vascular access function. In the present study, in patients with venous stenosis near an arteriovenous fistula (A-V fistula), a sensor was placed at different positions around the stenosis and shunt murmur signals obtained using a measurement system were subjected to time–frequency analysis based on wavelet transforms. The shunt murmurs obtained from the stenotic region closely represented some features of murmurs that are often referred to as “high-pitch” murmurs in the clinical setting. In contrast, shunt murmurs obtained about 5 cm downstream of the stenotic region closely represented some features of murmurs that are often referred to as “low-pitch” murmurs in the clinical setting. Furthermore, with the aim of extending the lifespan of arteriovenous grafts (A-V grafts) by detecting and treating stenotic lesions before the A-V graft becomes occluded, we evaluated the possibility of utilizing the present shunt murmur analysis for monitoring stenosis in such A-V grafts. When shunt murmurs from patients with A-V grafts were analyzed, the results suggested that the blood flow through the venous anastomosis of the graft was the most turbulent. This present method whereby blood flow in an A-V fistula is assessed based on the frequency distribution on a time–frequency plane by wavelet transform analysis is advantageous because findings are not markedly affected by sensor attachment. Furthermore, because the sensor is attached using an adhesive collar, measurements can be taken over a short period of time before each dialysis session.