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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.

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The prevalence of antihepatitis virus C (HCV) antibodies in chronic hemodialysis (HD) patients is higher than in normal populations, and yet hepatocellular carcinoma (HCC) is infrequent in chronic HD patients who are HCV antibody positive. In this study, we investigated the characteristics of HCV-antibody-positive patients with HCC on chronic HD. A total of 6,366 cases of HCV-antibody-positive patients on chronic HD therapy was analyzed on the basis of answers to questionnaires on the incidence rate of HCC in 314 Japanese dialysis institutions. HCC was a complication in 114 of 6,222 (1.8%) HCV-antibody-positive patients, and cirrhosis was a complication in 536 of 6,242 (8.6%). The incidence rate of both complications was significantly higher in males than in females, and the incidence rate in the chronic HD patients was much lower than in normal populations. Specific immunological status in patients on chronic HD therapy may be an important key for preventing the progression of chronic HCV hepatitis. However, further research is needed because this study was preliminary and excluded the type of HCV virus, pathological findings, and laboratory data.

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In a typical double filtration plasmapheresis treatment, plasma fractionation between albumin and some immunoglobulins associated with toxins is limited because none of the currently available plasma fractionators has a strict cutoff property for these proteins. Selectivity of immunoglobulins over albumin depends not only on the cutoff properties of the membrane but on the operating conditions such as the flow rate of the supplied plasma (Q(P)) and retained plasma to be discarded (Q(D)) in the plasma fractionator. We carried out an in vitro study using human plasma harvested by single plasma exchange treatments to assess the selectivity of a plasma fractionator, Evaflux 2A-F (Kawasumi Laboratories, Inc., Tokyo, Japan), under various operating conditions. The results of rate-constant filtration experiments showed that the concentrations in the feed tank and the sieving coefficient (SC) values of every protein were decreased slightly within 2 h after the start of the experiment because of membrane trapping, adsorption, and/or plugging. The time-averaged SC value of albumin increased with flow rate ratio (Q(P)/Q(D)) due to increasing filtration fraction (FF), but relative removal efficiency (mD/mP*) for albumin decreased with Q(P)/ Q(D) due to decreasing Q(D). For immunoglobulins, on the other hand, the SC values were almost unchanged, and the mD/mP* values increased with Q(P)/Q(D) due to an increase in FF. Both increasing Q(P) and decreasing Q(D) are effective means of improving selectivity between these proteins in the plasma fractionator. Membrane fouling is, however, obvious beyond a Q(P)/Q(D) value that is thought to be a critical point. Operation should be conducted below the critical Q(P)/Q(D) value, which depends on the patient's plasma components and the cutoff property of the membrane.

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Botulism is a paralytic disease caused by a toxin produced by the bacterium Clostridium botulinum. Outbreaks of the illness take place with a mortality rate of 10%, and the potential terrorist use of the toxin has become a serious concern. The current treatment includes administration of antitoxin, which can cause serious allergic reactions. Recently, we have successfully treated a 64 year old woman with the illness with IMMUSORBA TR350 (Asahi Medical, Tokyo, Japan), an extracorporeal adsorptive column containing polyvinylalcohol-tryptophan as an adsorptive agent, which has been widely used in Japan to treat myasthenia gravis and Guillain-Barre syndrome. Initially, the patient developed ocular muscle weakness and a variant of the Guillain-Barre syndrome was suspected. After extracorporeal treatment, her neurologic symptoms remarkably improved. After a series of treatments, botulinum toxin type B was isolated in the food she had eaten, establishing the diagnosis. An in vitro study revealed that the adsorptive column removed botulinum toxin to a significant extent. Our recent findings suggest that treatment with the adsorptive column TR350 can be a feasible option for botulism, which is a rare but potentially lethal disease.

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Because of a shortage of cadaver donors in Japan, ABO-incompatible living kidney transplantation has been carried out. Sixty-seven ABO-incompatible living kidney transplantations (LKT) were performed between January 1989 and December 1995 at our institution. In our previous report on the long-term results of ABO-incompatible LKT, graft survival of ABO-incompatible LKT up to 3 years was significantly lower than that of ABO-compatible LKT, but no significant difference was seen from 4 to 8 years. We removed anti-A/B antibodies by immunoadsorption and/or double filtration plasmapheresis before kidney transplantation. There was a significant difference between the anti-A/B antibody titers before and after plasmapheresis. The anti-A/B antibody titers also were well suppressed over the long term after transplantation.

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The purpose of this study was to determine the perioperative factors that influence patient and graft outcome in living-related liver transplantation (LRLT). Between April 1995 and October 1998, we performed a series of 46 LRLT procedures, including 11 adult cased, at our institute. Mean age and weight of the recipients were 12.0 +/- 2.3 years and 23.7 +/- 2.6 kg, respectively. Seven out of the 46 patients had renal failure and received hemodialysis therapy before and after LRLT or kidney transplantation. The recipients were divided into two groups: those who survived for 7-48 months after LRLT (group 1, n = 36), and those who died within 4 months after surgery (group 2, n = 10). Factors analyzed included recipient age and weight, graft/recipient body weight ratio (G/R ratio), emergent vs elective surgery, United Network for Organ Sharing (UNOS) status, presence of preoperative plasmapheresis (PEX) and renal failure, and so on. Recipients in group 1 compared with group 2 had less advanced liver disease (i. e., a lower rate of emergent surgery, 14% vs 50%, and fewer patients with UNOS status 1, 14% versus 70%; P < 0.05 and P < 0.001, respectively). Group 1 recipients also had a lower percentage of preoperative treatment with plasmapheresis (22% vs 70%, P < 0.01). However, neither the G/R ratio nor the presence of renal failure affected the patient survival rate. In conclusion, factors independently associated with reduced patient survival after LRLT include emergent surgery, Child-Pugh class, UNOS status 1, and preoperative plasmapheresis.

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Two long-term renal transplant survivors, for about 20 yr, with unusual histological features in the allograft kidney are reported. In both cases, marked hyalinosis was observed in the arterioles of the transplanted kidney, despite never having been administered cyclosporine or tacrolimus. The cause remains unknown at the present time, but we think that the changes could be multifactorial in origin, including due to aging of the graft, hypertension, hyperlipidemia and chronic rejection. We conclude that histological analysis of the allograft kidney must be performed in long-term renal transplant survivors, in order to understand the histological changes in the chronic phase after kidney transplantation and to predict the prognosis of the graft.

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