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There is a lack of adjudicated and prospectively randomized published outcomes on the use of drug-coated balloons (DCB) to treat dysfunctional arteriovenous fistula in Asian patients. This post-hoc subgroup analysis of 112 Japanese participants from the global IN.PACT AV Access trial reports outcomes through 12 months.Participants were treated with DCB (n=58) or standard non-coated percutaneous transluminal angioplasty (PTA) balloons (n=54). Outcomes included target lesion primary patency (TLPP), access circuit primary patency, and safety.Through six months, TLPP was 86.0% (49/57) in the DCB group and 49.1% (26/53) in the PTA group (p0.001). Through twelve months, TLPP was 67.3% (37/55) in the DCB group and 43.4% (23/53) in the PTA group (p=0.013).In this post-hoc analysis of Japanese participants from the IN.PACT AV Access trial, participants treated with DCB had higher TLPP through 6 and 12 months compared to PTA. This article is protected by copyright. All rights reserved.

Information regarding new-onset posttransplant psychotic disorders and their effect on nonadherence and posttransplant outcome is quite limited. We report a case of new-onset posttransplant schizophrenia that led to death. The patient, a woman with Wilson disease but no history of psychiatric problems or a substance use disorder had undergone liver transplantation at age 21. She married subsequently and bore children, being well able to handle her housework, child care, and full-time employment. She continued her medications as prescribed, and good graft function was maintained. At age 41, she experienced an episode of schizophrenia, then graft loss associated with nonadherence to immunosuppressive agents. Death ensued, occurring 6 months after the onset of schizophrenia. This case highlights the possibility that schizophrenia manifesting long after liver transplantation can result in graft loss and death due to medication nonadherence. Thus, awareness of the possibility of this rare clinical scenario is critical.

The need for donor pool expansion remains an important task for kidney transplantation. The aim of this study is the evaluation of primary nonfunction (PNF) from donation after circulatory death (DCD) kidneys.Between 1996 and 2017, 100 kidney transplants from DCD donors were conducted in our department. We retrospectively analyzed PNF of kidney transplant recipients from DCD donors in terms of donors' and recipients' epidemiologic characteristics.Of 100 grafts, 95 recipients (95.0%) had discontinued hemodialysis at the time of hospital discharge. Only 5 recipients (5.0%) developed PNF. All 5 PNF recipients received a single graft from an expanded criteria donor (ECD). The mean donor age in the PNF group was 65.0 (SD, 6.2) years. Significant differences between the PNF group and discontinued dialysis group were found for donor age (P .01) and for the use of ECD kidneys (P .02). Nevertheless, no significant difference was found between groups for several factors: a history of hypertension and cerebrovascular events, terminal creatinine levels, and graft weight.The incidence of PNF from DCD kidneys was very low. Although ECD kidneys in older donors might be a significant risk factor for PNF, these findings suggest that DCD kidneys should be used more frequently for donor expansion.

Mycophenolate mofetil has improved long-term outcomes of kidney transplantation. However, the impact of mycophenolic acid (MPA) trough level on the development of de novo donor-specific anti-HLA antibody (DSA) is unclear. We examined the relation between MPA trough level and de novo DSA development.We retrospectively studied 617 kidney recipients whose MPA trough level and de novo DSA data were available. All patients underwent primary kidney transplant from living donors from 2008 to 2014, and were chronically treated with a calcineurin inhibitor, mycophenolate mofetil, and +/- steroids. They were equally divided into 4 groups according to the mean trough level of MPA (mMPA) at 1 year post-transplantation: Group 1, mMPA 2.14 ng/mL (n = 152); Group 2, mMPA 2.14-2.83 ng/mL (n = 157); Group 3, mMPA 2.83-3.57 ng/mL (n = 153); and Group 4, mMPA ≥ 3.57 ng/mL (n = 155). The groups were compared by incidence rate of de novo DSA, graft survival rate, and renal function.The incidence rates of de novo DSA were 33.3% in Group 1, 23.7% in Group 2, 22.9% in Group 3, and 30.3% in Group 4 (P = .158). Although there was no significant difference in graft survival rates, a significant difference of renal functions was noted: the higher the renal function, the lower the MPA trough level.The mMPA trough level at 1 year post-transplantation was not statistically associated with the incidence rate of de novo DSA after kidney transplantation.

No factors influencing the blood everolimus (EVL) concentrations has been identified until date. Our aim was to identify factors that can affect the ratio of the trough blood concentration to dose level (CWe retrospectively analyzed 448 patients who had undergone kidney transplantation and were subsequently being managed as our hospital between 2011 and 2015. Multivariate analysis were performed in an attempt to identify factors affecting the EVL CThe numbers of patients receiving calcineurin inhibitor (CNI)-free regimen and regimen containing cyclosporine (CsA) or tacrolimus (TAC) were 47, 137 and 264 respectively. The EVL CWe obtained an indication of patient characteristics that influences the EVL C

Background Although the outcome of kidney transplantation (KTx) has improved, various adverse effects of immunosuppressants and chronic rejection aggravate the long-term prognosis of patients. Therefore, the induction of immune tolerance may be an effective therapeutic strategy. Methods A clinical trial aiming at immune tolerance induction was conducted in kidney transplant recipients from HLA mismatched living donors by infusing autologous donor-specific regulatory T cells (Treg). To obtain Treg, recipient's peripheral blood mononuclear cells were cocultured with irradiated donor cells in the presence of anti-CD80/CD86 monoclonal antibody for 2 weeks. For preconditioning, splenectomy + cyclophosphamide (CP) was employed in the first series (group A; n = 9). In group B, splenectomy was substituted by preadministration of rituximab (group B; n = 3). In the latest cases, rituximab + rabbit antithymocyte globulin was administered instead of cyclophosphamide (group C; n = 4). Twelve days after KTx, the cultured cells were intravenously infused, and immunosuppressants were gradually tapered thereafter. Results Although mixed lymphocyte reaction was remarkably suppressed in a donor-specific fashion, 6 out of 9 patients from group A, 1 out of 3 from group B, and 1 out of 4 from group C developed acute rejection within 1 year after KTx. Complete cessation of immunosuppression was not achieved, and a small dose of immunosuppressants was continued. Conclusions The adoptive transfer of autologous ex vivo-expanded Treg is 1 of the options to possibly induce alloimmune hyporesponsiveness. However, in the present study, further regimen optimization is still required and should be the focus of future investigations.

Introduction: Extra efferent arterioles, also known as polar vasculosis (PV), are often observed in the glomerular vascular pole and are associated with glomerular hypertrophy, indicating early recurrent diabetic kidney disease (DKD) in renal allografts. However, its significance in patients without diabetes remains uncertain. Methods: A total of 9,004 renal allograft biopsy specimens obtained between January 2007 and December 2017 at Tokyo Women’s Medical University were retrospectively analyzed to examine the clinical and pathological significance of PV in renal allografts. PV was identified in 186 biopsy specimens obtained from 165 patients. The PV group comprised 46 patients; 35 patients without DKD and 11 patients with DKD as the initial cause of ESRD, whose clinical information was available and treated with the calcineurin inhibitor (CNI) tacrolimus. The non-PV group comprising patients with renal allografts matched for age and postoperative day included 93 patients without DKD and 16 patients with DKD as the initial cause of ESRD. Results: In patients with nondiabetic renal allografts, systolic blood pressure was significantly higher in the PV group than in the non-PV group. The trough tacrolimus levels during the overall study period and at 2 weeks, 1 month, and 2 years after transplantation were significantly higher in the PV group compared with the non-PV group. Glomerulomegaly was significantly more common. Moreover, ah and aah scores in Banff score were significantly higher in the PV group than in the non-PV group. In those with diabetic renal allografts, although the clinical parameters and tacrolimus trough levels in all time periods were not significantly different between the PV and non-PV groups, the ah score was significantly higher in the PV group. Conclusion: PV was associated with CNI toxicity in nondiabetic but not in diabetic renal allografts. The pathogenesis of PV in renal allografts is considered to be multifactorial.

We developed a preoperative assessment system to predict surgical workload in hand-assisted laparoscopic donor nephrectomy (HALDNx) using the normal-based linear discriminant rule (NLDR). A total of 128 cases of left HALDNx performed by a single operator were used as training data. Surgical workload was measured by operative time. The optimized model had 9 explanatory variables: age, total protein, total cholesterol, number of renal arteries (numberRA), 4 variables of perinephric fat (PNF), and thickness of subcutaneous fat. This model was validated using cross-validation and the .632 estimator to estimate discrimination rates with future test data. PNF and numberRA were the predominant factors affecting workload followed by the computed tomography value of PNF, body weight, and male sex. The estimated accuracy of the prediction system was 94.6%. The complication rate was 9.38% and did not correlate with surgical workload. We also made our program available online for constructing assessment functions from other cohort data. In conclusion, the surgical workload of HALDNx could be predicted with PNF and numberRA as the dominant risk factors.

Management of children with autosomal recessive polycystic kidney disease (ARPKD) who develop end-stage renal disease (ESRD) remains challenging because of concomitant liver disease. Patients with recurrent cholangitis are candidates for liver-kidney transplantation, while the treatment for patients with splenomegaly and pancytopenia due to portal hypertension is controversial. Herein, we report 7 children who were treated using an individualized treatment strategy stratified by liver disease. Two patients with recurrent cholangitis underwent sequential liver-kidney transplantation, while 4 patients with splenomegaly and pancytopenia but without recurrent cholangitis underwent splenectomy followed by isolated kidney transplantation. The remaining patient, who did not have cholangitis and pancytopenia, underwent isolated kidney transplantation. Blood cell counts were normalized after splenectomy was performed at the median age of 8.7 (range, 7.4-11.7) years. Kidney transplantation was performed at the median age of 8.8 (range, 1.9-14.7) years in all patients. Overwhelming post-splenectomy infections and cholangitis did not occur during the median follow-up period of 6.3 (range, 1.0-13.2) years. The estimated glomerular filtration rate at the last follow-up was 53 (range, 35-107) mL/min/1.73 m2 . No graft loss occurred. Our individualized treatment strategy stratified by recurrent cholangitis and pancytopenia can be a feasible strategy for children with ARPKD who develop ESRD and warrants further evaluation.

Background Tubular basement membrane immune deposits (TBMID) has rarely been observed in renal allografts. It is usually found in BK virus nephropathy and immune complex glomerulonephritis; however, its significance is not well understood. We conducted a retrospective clinicopathological study on monoclonal immunoglobulin G (IgG) TBMID. Methods We studied 7177 renal allograft biopsy specimens obtained from Tokyo Women’s Medical University from 2007 to 2015 and performed light microscopic, electron microscopic and immunofluorescence studies. Results Tubular basement membrane (TBM) deposits of IgG were found in 73 biopsies from 61 patients and the IgG subclass was obtained in 31 biopsies. There were no cases of monoclonal IgA or IgM TBMID. In total, 13 biopsies from 10 patients showed monoclonal IgG TBMID. Of these, seven showed monoclonal IgG1κ TBMID and one each showed monoclonal IgG2κ, IgG2λ and IgG3κ TBMID. Conversely, eight patients showed polyclonal IgG TBMID. In electron microscopy, large granular electron-dense deposits (EDDs) in the TBM were detected in all patients with monoclonal IgG1κ TBMID. EDDs were absent in TBM in patients with monoclonal IgG2κ, IgG2λ or IgG3κ TBMID. Progression of interstitial fibrosis and tubular atrophy (IFTA) was significantly higher in patients with monoclonal IgG1κ TBMID than in those with polyclonal IgG TBMID (P

BACKGROUND Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection characterized by the presence of mature plasma cells. In general, the prognosis of PCAR is poor, and its clinical and pathological features remain unclear. METHODS We performed a retrospective observational study and compared allograft survival between kidney transplant recipients who developed PCAR and those who did not develop PCAR. We further analyzed clinical and pathological risk factors for allograft failure in PCAR patients. RESULTS Of 1956 recipients, 40 developed PCAR. There was a higher prevalence of deceased donor transplants (27.5% vs 11.7%, P = 0.0059), longer median total ischemia time (99 minutes; interquartile range, 71-144 vs 77 minutes; interquartile range, 59-111; P = 0.0309), and lower prevalence of ABO-incompatible transplantation (7.5% vs 22.5%; P = 0.0206) in patients with PCAR than in those without PCAR.Multivariate Cox regression analysis showed that development of PCAR was associated with allograft loss (hazard ratio, 8.03; 95% confidence interval, 3.89-14.80; P < 0.0001).We classified PCAR according to the Banff 2015 criteria into a borderline change group, a T cell-mediated rejection (TCMR) group, an antibody-mediated rejection (AMR) or suspected of having AMR (AMR/sAMR) group, and a mixed rejection (TCMR/AMR) group. The AMR/sAMR group was associated with a lower rate of allograft survival without significant difference (log-rank test, P = 0.1692). CONCLUSIONS The results indicated that PCAR was an independent risk factor for allograft loss. PCAR presented with all types of rejection in the Banff 2015 criteria, and AMR/sAMR was associated with poor allograft survival.

We report a case of rapid recurrence of immunotactoid glomerulopathy (ITG) with monoclonal IgG3κ deposits in a transplanted renal graft.

Background In Japan, it has been reported that an increase in atmospheric pressure is associated with a higher incidence of acute appendicitis. The aim of this epidemiologic study was to investigate the association between climatic elements and the incidence of acute appendicitis. Materials and methods A case-crossover design was used in the present study. Two wk before diagnosis was used for the target period. The same 2-wk period, but 1, 2, and 3 y before diagnosis, was used for the control period. The study participants were patients with acute appendicitis (10-29 y) from 14 facilities in the Greater Tokyo Area. Mean of the observed values for atmospheric pressure, temperature, relative humidity, and hours of sunshine calculated for each target and control period were used as climatic elements to investigate trends 1 and 2 wk before diagnosis. Results The year of diagnosis, a statistically significant moderate upward trend in atmospheric pressure was observed during the 2-wk period before diagnosis of acute appendicitis (tau = 0.47; P = 0.0213), whereas a weak nonsignificant downward trend was observed 1 y before diagnosis (tau = −0.29; P = 0.1596), and weak nonsignificant upward trends were observed 2 (tau = 0.24; P = 0.2505) and 3 y (tau = 0.28; P = 0.1634) before diagnosis. Conclusions An association was found between atmospheric pressure and the incidence of acute appendicitis. However, no significant differences were found in relation to sex or age. These findings suggest that changes in atmospheric pressure are associated with the likelihood of patients visiting the hospital.

Combined liver-kidney transplantation (CLKT) is well established as a definitive therapy with the potential to provide complete recovery for certain liver-kidney diseases, although the results might be contingent on the cause of transplantation. The purposes of the present study were to review the longterm outcome of renal allografts in CLKT patients from single living donors and to investigate the beneficial factors, compared with solitary renal transplantation. Thirteen patients underwent sequential liver transplantation (LT) and kidney transplantation (KT) from single living donors. The indications for KT were oxaluria (n = 7), autosomal recessive polycystic disease (n = 3), and others (n = 3). The same immunosuppressive regimen used after LT was also used after KT. KT was performed between 1.7 and 47.0 months after the LT. The overall patient survival rate was 92.3% at 10 years. In 12 of the 13 surviving patients, the renal allografts were found to be functioning in 11 patients after a mean follow-up period of 103.6 months. The death-censored renal allograft survival rate at 10 years was 100%, which was better than that of KT alone (84.9%) in Japan. Immunological protection conferred by the preceding liver allograft may have contributed to the longterm outcomes of the renal allografts. In addition, the donation of double organs from a single living and related donor may have a favorable impact on the graft survival rate. In the future, investigations of factors affecting the longterm outcome of renal allografts, including details of the involvement of de novo donor-specific antibody, will be needed. Liver Transplantation 23 315-323 2017 AASLD.

This study was conducted to evaluate de novo donor-specific anti-human leukocyte antigen (HLA) antibody (dnDSA) production leading to antibody-mediated rejection (ABMR) after rituximab induction in non-sensitized ABO-compatible living kidney transplantation (ABO-CLKTx). During 2008-2015, 318 ABO-CLKTx were performed at the Department of Surgery III at Tokyo Women's Medical University Hospital. To reduce confounding factors, we adopted a propensity score analysis, which was applied with adjustment for age, gender, duration of pretransplant dialysis, HLA mismatch count, preformed DSA, non-insulin-dependent diabetes mellitus, immunosuppressive treatment, and estimated glomerular filtration rate (eGFR) on postoperative day 7. Using a propensity score matching model (1:1, 115 pairs), we analyzed the long-term outcomes of 230 ABO-CLKTx recipients retrospectively. Recipients were classified into a rituximab-treated (RTX-KTx, N = 115) group and a control group not treated with rituximab (C-KTx, N = 115). During five years, adverse events, survival rates for grafts and patients, and incidence of biopsy-proven acute rejection (BPAR) and dnDSA production for the two groups were monitored and compared. All recipients in the RTX-KTx group received rituximab induction on preoperative day 4 at a single fixed low dose of 100 mg; the CD19+ B cells were eliminated completely before surgery. Of those recipients, 13 (11.3%) developed BPAR; 1 (0.8%) experienced graft loss. By contrast, of C-KTx group recipients, 25 (21.7%) developed BPAR; 3 (2.6%) experienced graft loss. The RTX-KTx group exhibited a significantly lower incidence of BPAR (P = .041) and dnDSA production (13.9% in the RTX-KTx group vs. 26.9% in the C-RTx group, P = .005). Furthermore, lower incidence of CMV infection was detected in the RTX-KTx group than in the C-KTx group (13.9% in the RTX-KTx group vs. 27.0% in the C-KTx group, P = .014). No significant difference was found between groups for several other factors: renal function (P = .384), graft and patient survival (P = .458 and P = .119, respectively), and the respective incidences of BK virus infection (P = .722) and leukopenia (P = .207). During five-year follow-up, single fixed low-dose rituximab therapy is sufficient for ensuring safety, reducing rejection, and suppressing dnDSA production for immunological low-risk non-sensitized ABO-CLKTx.

Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m2 at day −14 and day −1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

Background. Focal segmental glomerulosclerosis (FSGS) often develops rapidly and frequently progresses to renal failure, while the recurrence rate after kidney transplantation is 20–50%. We performed low-density lipoprotein (LDL) apheresis before kidney transplantation in FSGS patients to prevent recurrence. Methods. Five adult patients with chronic renal failure due to FSGS undergoing living related donor kidney transplantation were investigated retrospectively. LDL apheresis was done 1-2 times before transplantation. Postoperative renal function and recurrence of FSGS were assessed. Results. The patients were two men and three women aged 24 to 41 years. The observation period ranged from 60 days to 22 months. Preoperative LDL apheresis was performed once in one patient and twice in four patients. Blood LDL cholesterol levels were normal before LDL apheresis and remained normal both after LDL apheresis and after kidney transplantation. Additional LDL apheresis was performed once in one patient with mild proteinuria after transplantation. The renal graft survived in all patients and there was no evidence of recurrent FSGS. Conclusions. Although the observation period was short, FSGS did not recur in all 5 patients receiving preoperative LDL apheresis. These results suggest that LDL apheresis can be effective in preventing recurrence of FSGS after kidney transplantation.

Introduction The number of renal transplantations performed for patients with chronic kidney disease has increased in Japan, but little is known about the outcomes in those who subsequently undergo video-assisted thoracoscopic surgery (VATS). We therefore investigated the outcomes of consecutive patients requiring VATS after renal transplantation at our institute. Methods We retrospectively collected the clinical data for patients undergoing VATS after renal transplantation between January 2003 and September 2014. Specifically, we compared the serum creatinine level and estimated glomerular filtration rate preoperatively and postoperatively, and investigated the postoperative complications. Results In total, 12 patients underwent VATS after renal transplantation during the study period. All patients received two or three immunosuppressive agents. Operative methods used included VATS wedge resection (n = 4), segmentectomy (n = 4), lobectomy (n = 2), mediastinal tumor resection (n = 1), and chest wall tumor resection (n = 1). No patients required perioperative hemodialysis. There were no intraoperative complications, but one patient developed postoperative hemorrhagic cystitis and another developed pneumonia. One patient developed pneumocystis pneumonia 2 months after left lower lobectomy and required hemodialysis. No further hemodialysis was required by any patient. Of note, no statistically significant differences were observed between the preoperative and postoperative serum creatinine level (P = 0.666) and estimated glomerular filtration rate (P = 0.388). There were no in-hospital deaths. Univariate analysis revealed no significant risk factors for postoperative complications. Conclusion This report showed favorable results for VATS after renal transplantation. However, clinicians must remain vigilant for complications because transplant recipients remain permanently immunocompromised.

Wiskott-Aldrich syndrome, a rare X-linked hereditary syndrome, is characterized by immunodeficiency, thrombocytopenia, and eczema. The underlying T-cell defect renders renal transplantation and immunosuppressive treatments uncertain. The present case exhibited the mild clinical manifestation, regarded as X-linked thrombocytopenia. He successfully underwent a living-donor ABO-compatible renal transplantation and splenectomy in 2002, and thereafter experiencing no severe rejection, serious infection, or malignancy for more than 10 years. Though IgA nephropathy was detected 8 months after transplantation, the patient's renal function and proteinuria were stable without any treatment. The present case showed a successful long-term graft survival and the importance of splenectomy added to renal transplantation.

A 45-year-old woman with type 1 diabetes and chronic renal failure on dialysis underwent simultaneous pancreas-kidney transplantation from a brain dead donor. On postoperative day 15, acute generalized peritonitis was diagnosed and emergency laparotomy was performed. Perforation of the donor duodenum was found, which had apparently resulted from duodenal compression by the tip of the intestinal fistula tube placed for decompression. The perforation was sutured and the intestinal fistula tube was exchanged. Following this, perforation repeatedly recurred at the same site and open repair at laparotomy was required a total of four times. The fourth operation involved both suturing the perforation and covering it with ileum, after which there was no further recurrence. The patient was discharged on posttransplantation day 219, with the pancreas and kidney grafts both functioning well. This report presents a rare complication of simultaneous pancreas-kidney transplantation.

A 46-year-old Japanese woman on dialysis for type 1 diabetes and chronic renal failure underwent simultaneous pancreas and kidney transplantation from a brain-dead donor. On postoperative day 3, ilio-femoral deep vein thrombosis on the side of pancreatic transplantation was diagnosed from swelling of the right leg, an increased D-dimer level, and imaging findings. Anticoagulant therapy was initiated to prevent proximal propagation of the thrombosis and pulmonary thromboembolism. However, gastrointestinal bleeding occurred, which was thought to be due to mucosal bleeding from the duodenal graft. Her anticoagulant therapy was adjusted and hemostasis was conducted, controlling the gastrointestinal bleeding without surgical intervention. Blood flow was maintained to both grafts and graft function was good. When gastrointestinal bleeding occurs during anticoagulant therapy for deep vein thrombosis after combined pancreas and kidney transplantation, bleeding can be controlled by adjusting anticoagulant therapy and other appropriate measures.

The cryopyrin-associated periodic syndrome (CAPS) is an autosomal dominant autoinflammatory disease characterized by fever, skin rash, and joint involvement with acute inflammatory response. The genetic defect involves the NLRP3 gene that encodes cryopyrin and leads to an abnormal production of interleukin-1 (IL-1). Therefore, anti-IL-1 treatment represents an effective therapy. One of the most severe manifestations of the disease is secondary amyloidosis that causes renal failure. We present a patient with CAPS who underwent renal transplantation for renal insufficiency caused by amyloidosis. The function of the transplanted kidney deteriorated because of the late administration of IL-1 receptor antagonist, anakinra. This case may indicate the importance of early initiation of anti-IL-1 treatment in CAPS patients who have undergone kidney transplantation.

Post-transplant hyperglycaemia of diabetic patients may cause recurrent diabetic kidney disease (DKD) in kidney allografts. We report a patient with slowly progressive DKD with calcineurin inhibitor toxicity (CNI) toxicity after the kidney transplantation. A 28-year-old female with type 1 diabetes mellitus underwent successful kidney transplantation from her mother in April 2003, and the kidney graft survived for more than 10 years. She was treated with combined immunosuppressive therapy consisting of cyclosporine and mycophenolate mofetil. After transplantation, she continued to take insulin injection four times per day, but her glycosylated haemoglobin (HbA1c) was above 10%. Protocol allograft kidney biopsies performed 5 and 10 years after transplantation revealed the recurrence of slowly progressive diabetic kidney disease. In addition, arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity (CNI) was detected with progression. Post-transplant hyperglycaemia causes recurrent diabetic kidney disease (DKD) in kidney allografts, but its progression is usually slow. For long-term management, it is important to prevent the progression of the calcineurin inhibitor arteriolopathy, as well as maintain favourable glycaemic control.

The effect of an anti-human leukocyte antigen-DR (MHC class II) humanized monoclonal antibody, IMMU-114, against the human to bovine cellular response was investigated. Methods Human peripheral mononuclear cells (PBMCs) were cocultured with inactivated self-PBMCs (Self), bovine PBMCs with control antibody (Xeno), or bovine PBMCs with IMMU-114 (IMMU-114). Cellular responses were investigated by thymidine incorporation assay, CFSE (carboxyfluorescein diacetate succinimidyl ester)-mixed lymphocyte reaction, and cytokine production in culture medium. Results Thymidine incorporation rates at a 1:1 responder to stimulator ratio for Xeno + control antibody, Xeno + IMMU-114, Self + control antibody, and Self + IMMU-114 were 14201.3 ± 1968.4, 513.0 ± 49.5, 952.7 ± 128.7, and 423.3 ± 138.8 cpm, respectively (P = 0.032). Those at a 1:2 ratio were 6518.0 ± 690.1, 896.6 ± 92.9, 1051.0 ± 123.6, and 736.0 ± 35.6 cpm, respectively (P = 0.036). CFSE-mixed lymphocyte reaction demonstrated that the frequencies of CFSE-low, CD4+, and CD25+ activating T cells in Self, Xeno, and IMMU-114 were 0.27 ± 0.04%, 3.65 ± 0.53%, and 1.23 ± 0.15%, respectively (P = 0.027). Cytokine production in culture medium indicated that IMMU-114 decreased Th1-type cytokines, including interleukin-2, interferon-γ, and tumor necrosis factor-α. Conclusion IMMU-114 effectively suppresses human to bovine cellular responses. The mechanism involves direct inhibition of the interaction between class II human leukocyte antigen-DR-positive cells and CD4+ T cells, and indirect suppression of Th1 cytokine production.

BACKGROUND While kidney transplantation (KTx) reverses many disorders associated with end-stage renal disease (ESRD), patients who have received KTx often have chronic kidney disease and bone and mineral disorder (CKD-MBD). However, it is unknown how bone metabolism changes by KTx. PATIENTS AND METHODS Living donor-KTx recipients (n = 34) at Tokyo Women's Medical University were prospectively recruited and the levels of bone-specific alkaline phosphatase (BAP) and serum cross-linked N-telopeptides of Type 1 collagen (NTX) were measured before, 6 and 12 months after transplantation. RESULTS Before KTx, serum BAP was within the reference range in more than half of patients while NTX was high in most patients. Serum NTX was higher in patients with longer dialysis durations compared to that with shorter durations before KTx. However, there was no difference in serum BAP between these patients. After KTx, BAP increased while NTX decreased along with the decline of PTH. In addition, the numbers of patients who showed high BAP and NTX were comparable after KTx. CONCLUSION These results suggest that bone formation is suppressed and uncoupled with bone resorption in patients with ESRD and this uncoupling is restored by KTx. Further studies are necessary to clarify the mechanism of bone uncoupling in patients with ESRD.

Background: The aim of this study was to elucidate the clinical characteristics and frequency of psychiatric consultation in a routine clinical setting after kidney transplantation. Methods: Subjects were 1,139 consecutive recipients who received kidney transplantation at our hospital between January 1997 and September 2006. The hospital patient database was searched to determine whether these recipients received psychiatric consultation after their transplantation during this period. Results: Among 1,139 recipients, 118 (10%) received psychiatric consultation after their transplantation. There were significantly more women among these recipients ( p = 0.036). Many of the recipients had received psychiatric consultation before transplantation ( p < 0.0001) and had received dialysis for a long time ( p = 0.018). There were three main psychiatric diagnoses according to ICD-10 diagnostic criteria in these 118 recipients: 42 (36%) had neurotic, stress-related, and somatoform disorders (F4); 35 (30%) had organic, including symptomatic, mental disorders (F0); and 27 (23%) had mood (affective) disorders (F3). The median length of time between kidney transplantation and initial psychiatric consultation was 57 days (interquartile range: 10–650 days). The lengths were 7 days (6–17 days) for F0, 75 days (18–650 days) for F4, 243 days (35–1,004 days) for F3, and 253 days (10–1,393 days) for other diagnostic groups. Significant differences were observed among these four groups (Jonckheere-Terpstra test, p < 0.001). Conclusion: Our results show that appropriate psychiatric intervention is necessary not only in early stages after kidney transplantation but also over the long term.

Objective We reviewed the introduction of a new, minimally invasive, live kidney donation program in our department. Methods The operating times of 700 consecutive hand-assisted laparoscopic donor nephrectomies (HALDN) conducted from February 2001 to April 2010 were examined. The risk factors for prolonging operating times were analyzed and major surgical barriers in HALDN investigated. Results All procedures were successfully performed without the requirement for conversion to open surgery or blood transfusion. The overall prevalence of perioperative complications was 3.0%, with no mortality, in this non-obese donor population with mean body mass index (BMI) as low as 23.2 ± 3.2 kg/m2. After the initial learning curve, a second learning plateau was detected until around case 300. Multivariate analyses showed that the significant risk factors were male sex, graft weight, number of renal arteries, right nephrectomy, and previous epigastric surgery (p

Background Renal transplantation (RTx) in carriers of human T-cell lymphotropic virus type 1 (HTLV-1) has a risk of developing overt leukemia upon immunosuppression. Although there have been a few reports of such cases, it is unclear HTLV-1 carrier if patients on the modern immunosuppressants would develop HTLV-1-associated myelopathy or adult T-cell leukemia lymphoma. Methods We retrospectively reviewed the clinical outcomes of RTx in nine HTLV-1 carriers to assess a risk of developing leukemia from 2002 to 2011 using immunosuppression with a calcineurin inhibitor, mycophenolate mofetil (MMF), and steroid. The anti-CD25 monoclonal antibody basiliximab was used for induction. In two cases of ABO-incompatible RTx, the rituximab was also administered before RTx. Results The ratio of male to female subjects was 2 to 7 with an overall mean recipient age of 54.3 ± 8.1 years. We prescribed cyclosporine ( n = 5) or tacrolimus ( n = 4). There was only one graft loss due to the death caused by aspiration pneumonia with a functioning graft. No one developed overt leukemia with combined treatment with MMF, basiliximab and rituximab. Conclusion We concluded that RTx in HTLV-1 carriers could be performed using a modern immunosuppressive regimen, without the risk of developing leukemia.

Acute kidney injury (AKI) is not recognized as a major complication at the maintenance phase after kidney transplantation (KTx). Moreover, it is not clear whether the onset of AKI leads to graft failure. We examined the incidence of AKI that developed three months or later after KTx at our institute. We examined whether the incidence of AKI defined by the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage kidney disease criteria associates with graft failure by matched-pair Cox regression analysis. A total of 289 patients were available for the final analysis. The overall incidence of AKI was 20.4%, and the common etiology of AKI was bacterial infectious diseases. The group that developed AKI had significantly lower graft survival than non-AKI group independently of acute rejection. AKI Risk represented a high risk for graft failure and AKI Injury/Failure represented a higher risk for graft failure. The analysis by the AKIN classification yielded the similar results. These results indicate that AKI is a relatively common complication of KTx and represents the major risk for graft failure. We should make every effort in the prevention and early detection to avoid the occurrence of AKI and the subsequent graft failure after KTx.

Mineral and bone disorders (MBD), including hypercalcemia and hypophosphatemia, are common complications after renal transplantation; however, the natural course of these disorders has not been well documented, and the pathogenesis of persistent post-transplant MBD still remains elusive. This study was carried out to show the natural history of mineral metabolism in recipients after living-donor kidney transplantation and also to clarify post-transplant risk factors of persistent hypercalcemia and/or hypophosphatemia at 12months after transplantation. Living-donor kidney transplant recipients (N=34) at Tokyo Women's Medical University were prospectively and consecutively recruited. Parameters of MBD, including intact parathyroid hormone and full-length fibroblast growth factor23, were followed. Serum calcium levels increased until the fourth week post-transplantation, after which it reached a plateau; and serum phosphate decreased substantially at one week post-kidney transplantation, but recovered to the reference level at two months. Fibroblast growth factor23 gradually decreased to comparable levels for renal function, while hyperparathyroidism persisted for 12months after transplantation. Multivariate linear regression analysis revealed that intact parathyroid hormone was the best correlating factor with both hypercalcemia and persistent hypophosphatemia at 12months. This study suggests the need for testing of other interventions used for treatment of hyperparathyroidism which may help to offer better management of MBD after kidney transplantation.

Background. In 2002, we introduced the anti-CD20 chimeric antibody, rituximab, for ABO-incompatible kidney transplantation (ABO-IKT). Here, we report the 5-year outcome obtained using rituximab as part of the preoperative regimen for ABO-IKT. Methods. Between January 2002 and December 2008, 408 patients underwent living-related kidney transplantation at our department. The patients were divided into three groups: group A (n=280), ABO-compatible kidney transplantation (ABO-CKT); group B (n=63), ABO-IKT without rituximab induction; and group C (n=50), ABO-IKT with rituximab induction. Basic immunosuppression was the same in all three groups except for the use of rituximab, which was administered at 100 mg (n=6), 200 mg (n=26), and 500 to 1000 mg (n=18). Results. The graft survival rates in groups A, B, and C were 99.2%, 96.8%, and 100% at 1 year, 93.8%, 94.9%, and 100% at 3 years, and 88.4%, 90.3%, and 100% at 5 years after transplantation, respectively. Serum creatinine levels in the three groups were not different at 1, 3, and 5 years after transplantation. The numbers of episodes of acute antibody-mediated rejection in groups A, B, and C were 7 (2.5%), 10 (15.9%), and 2 (4.0%), respectively (P=0.651), and acute cellular rejection was observed in 40 (14.3%), 6 (9.5%), and 2 (4.0%) patients, respectively (P =0.0957). There was no increased risk of cytomegalovirus infection in group C. Conclusions. In the long term, inclusion of rituximab in the preoperative regimen yielded an even better outcome than that of ABO-CKT and rituximab-untreated ABO-IKT, without any increase in the risk of infection.

A case with graft function failure due to granulomatous interstitial nephritis and arteritis probably associated with a urinary tract infection by Pseudomonas aeruginosa within two months of kidney transplantation is reported. The recipient was a 42-yr-old male who had end-stage renal disease associated with chronic glomerulonephritis. He received a kidney transplant that was donated from a 54-yr-old male who died because of a subarachnoid hemorrhage. On the 60th day after operation, graft function failure occurred. A biopsy specimen showed granulomatous interstitial nephritis and vasculitis. At the same time, P. aeruginosa was detected by urine culture. The graft function is improved by treatment with the antibiotic faropenem for the urinary tract infection. On the basis of these clinical features, it was suggested that the present case developed granulomatous interstitial nephritis and arteritis associated with urinary tract infection by P. aeruginosa.

BACKGROUND To alleviate chronic renal graft shortages in Japan, donation after circulatory death (DCD) is an increasingly used organ resource. Organs from DCD donors with progressively increased terminal creatinine (t-Cr) levels are frequently used, but the effects of this condition on kidney transplantation (KTx) remain unclear. METHODS Between 1996 and 2013, 99 KTx from DCD donors were conducted in our department. Recipients were grouped according to the t-Cr (in mg/dL) of donors: group 1, t-Cr less than < 1.5; group 2, 1.5 ≤ t-Cr < 3.0; and group 3, t-Cr ≥ 3.0. We analyzed the long-term outcomes of KTx from DCD donors retrospectively in terms of donors' terminal renal function. RESULTS The respective mean donor t-Cr in groups 1, 2, and 3 were 0.73 ± 0.28, 2.02 ± 0.40, and 6.69 ± 3.68. The respective death-censored graft survival rates (%) in groups 1, 2, and 3 were 90.2, 96.2, and 86.7 at 1 year and 70.3, 86.2, and 73.4 at 10 years after transplantation. Group 1 exhibited lower incidence of delayed graft function than either group 2 or group 3 (80.5% vs 100% and 93.3%). Nevertheless, no significant difference was found between groups for several measures: Cr levels 1 month after KTx and lowest Cr levels throughout the observation period, prevalence of biopsy-proven acute rejection, and graft survival. Cox proportional hazard regression showed that donor age, cerebrovascular event, terminal urine output, and history of hypertension were significantly associated with graft survival. CONCLUSIONS Results suggest that, under certain conditions, kidneys from DCD donors with progressively increased t-Cr can be used safely with promising long-term outcomes.

Methods We conducted an analysis on 11 cases of death after AVG infection that occurred between 1996 and 2013, and compared their information with those of 23 cases of generalized infection due to arteriovenous graft (AVG) infection during the same period who survived. Results The cause of death was sepsis in all 11 patients. The initial C-reactive protein (CRP) was 10.2-39.8 (28 in average) and the duration from onset of fever to vascular access (VA) hemostasis/removal procedure was 6-9 days (6.4 days in average) in the 11 cases of death. Blood culture revealed a high frequency of methicillin-resistant staphylococcus aureus (MRSA) in 7 of the 11 cases of death. In contrast, in 23 survivors with VA infection and generalized infection, the CRP at the initial visit was 3.2-15.8 (5.6 in average) and the duration from onset of the fever to VA hemostasis/removal procedure was 0-5 days (2.6 days in average), and blood culture revealed a high frequency of methicillin-sensitive staphylococcus aureus (MSSA). Among the cases of death, although VA infection in the upper extremity itself resolved after removing the artificial vessel, they died without an improvement of sepsis. The reason why the sepsis did not resolve is that infectious foci were secondarily formed in other areas than the upper extremity because the start of treatment for VA infection was delayed. Conclusions Treatment for VA infection should be started as early as possible after onset to avoid the formation of secondary infectious foci in other areas.

Post-transplant hyperglycaemia of diabetic patients may cause recurrent diabetic kidney disease (DKD) in kidney allografts. We report a patient with slowly progressive DKD with calcineurin inhibitor toxicity (CNI) toxicity after the kidney transplantation. A 28-year-old female with type 1 diabetes mellitus underwent successful kidney transplantation from her mother in April 2003, and the kidney graft survived for more than 10 years. She was treated with combined immunosuppressive therapy consisting of cyclosporine and mycophenolate mofetil. After transplantation, she continued to take insulin injection four times per day, but her glycosylated haemoglobin (HbA1c) was above 10%. Protocol allograft kidney biopsies performed 5 and 10 years after transplantation revealed the recurrence of slowly progressive diabetic kidney disease. In addition, arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity (CNI) was detected with progression. Post-transplant hyperglycaemia causes recurrent diabetic kidney disease (DKD) in kidney allografts, but its progression is usually slow. For long-term management, it is important to prevent the progression of the calcineurin inhibitor arteriolopathy, as well as maintain favourable glycaemic control.

Background/Aims: Hepatitis C virus (HCV) infection is not rare in kidney transplant (KT) recipients. Interferon (IFN)-based therapies are generally contraindicated because IFN can induce severe rejection of the allograft. Here, we report five cases those who underwent therapy with direct-acting antiviral drugs (DAAs) after KT and evaluated their clinical outcomes. Patients/Methods: The five patients [the median age; 55 (49- 71) years, 3 males], were treated with NS5A and NS3 proteasetargeted DAA (daclatasvir, DCV and asunaprevir, ASV) therapy for 24 weeks after KT. The immunosuppressants prescribed were corticosteroids/mammalian target of rapamycin, tacrolimus, and mycophenolate mofetil or azathioprine. Results: In all cases, the acquired HCV was serological type 1 with the L31 or Y93 wild-type strain and the median HCV RNA level was 6.5 (5.7-6.7) log IU/mL. The median estimated glomerular filtration rate (eGFR) was 39 (30-58) mL/min/1.73 m2. All treated cases achieved a sustained virological response (SVR). Therapeutic drug monitoring of tacrolimus required slight adjustments of the tacrolimus dose. Regarding adverse events, a low-grade fever and mild renal dysfunction were observed in one case at 3 months. Despite withdrawing the treatment, this case still achieved SVR. The other cases showed no severe adverse events in liver or renal function. Conclusions: An IFN-free regimen of DCV/ASV therapy provided high tolerability and effectiveness in HCV-positive KT recipients, even under immunosuppressive conditions

Adverse effects of steroids have led to efforts to minimize their use in recipients of organ transplants. This study evaluated an early steroid withdrawal protocol including basiliximab, cyclosporine (CsA) and mycophenolate mofetil (MMF) in renal-transplant recipients.Between January 2001 and April 2005, our early steroid withdrawal protocol was used in 130 patients who underwent renal transplantation. Immunosuppression consisted of CsA (6-8 mg/kg), MMF (2 g/kg) and methylprednisolone (MP); basiliximab was given as induction therapy (steroid withdrawal group). MP was administered in a dose of 500 mg or 250 mg at renal transplantation; thereafter, the dose was rapidly tapered and MP was withdrawn on day 14 post-transplant.The incidence of acute rejection in the steroid withdrawal group was similar to that in the conventional steroid treatment group (without basiliximab) (18% vs. 21%). The severity of rejection episodes was similar in the two groups. Patient and graft survivals were 100% and 97% in the steroid withdrawal group. In 80 of the 130 patients (62%) in the steroid withdrawal group, MP was successfully withdrawn, with good allograft function during follow-up. In the other 50 patients (38%), MP was reinitiated because of acute rejection or other reasons. The success rate of steroid withdrawal 12 months after transplantation in recipients of ABO-compatible grafts was significantly higher than that in recipients of ABO-incompatible grafts (66% vs. 44%). The dose of MMF during the 12 months after renal transplantation was significantly lower in steroid reinitiated group than in the successful withdrawn group (p0.05). Patients in the successful withdrawn group showed metabolic benefits such as lower cholesterol levels as compared with the steroid reinitiated group.Although further follow-up is necessary to confirm our results, our protocol successfully permitted the early withdrawal of steroids in 62% of renal-transplant recipients, with no resumption of steroid treatment during 3 years of follow-up.

To enable successful ABO-incompatible kidney transplantation, reducing anti-donor blood-type antibody titer to below 1 : 16 just before the transplantation is considered to be indispensable. We performed successful ABO-incompatible kidney transplantation using new preconditioning regimen, consisting of rituximab, pretransplant splenectomy and plasmapheresis (PP) in 7 cases of non-responders to pretransplant PP. Rituximab was administered intravenously at a dose of 375 mg/M 2 weekly for 2–4 weeks, followed by laparoscopic splenectomy and 4 consecutive sessions of PP. The titer of anti-donor blood type antibody was reduced after PP and was below 1 : 8–1 : 16 on the day of the transplantation. CD19 + B cell rapidly decreased to below 1% in the peripheral blood samples and no B cell zone was found in spleen specimen, while CD79 + cell (plasma cell) was observed abundantly in the spleen. One case developed severe neutropenia with high fever probably due to cytomegalovirus (CMV) antigenemia and/or streptococcal bacteremia following twice infusion of rituximab, and both of which were resolved and kidney transplantation was done successfully. No other serious adverse effect was encountered except only one episode of cellular rejection and CMV antigenemia in two cases. Otherwise posttransplant course was smooth in all 7 cases. The kidney grafts were functioning well in all 7 cases during the observation period (13–44 months).

目的: この試験の目的はテルモ社が開発した再シール性の高い材料を用いた新しい透析用人工血管 (以下, GRASIL®) を臨床使用し, 移植後の長期成績を評価することである. 試験デザイン: 慢性腎不全患者71例に対し, GRASIL®を移植した. 累積開存率はKaplan-Meier法を用いて算出し, 移植後36か月以上 (最長54か月) フォローアップした. GRASIL®の開存率と合併症などを検討し, 本人工血管の臨床上の特長について評価を行った. 結果: 患者背景は男性36名, 女性35名, 移植時の年齢31-88歳 (平均年齢64.1±13.1歳, 中央値65歳) で透析歴は0-31年7か月 (中央値3年9か月) であった. 移植後12か月時点での累積一次開存率は46.3%, 二次開存率は80.4%および三次開存率は91.6%であり, 24か月時点での累積一次開存率は26.4%, 二次開存率は63.7%および三次開存率は83.3%, また, 36か月時点では累積一次開存率は18.5%, 二次開存率は50.0%, 三次開存率は71.4%であった. フォローアップ期間中, 閉塞は17例, 死亡は15例であり, バスキュラーアクセス関連の合併症は16例で18件発生した. 初回穿刺の最短は移植日当日で, 平均は9.8日 (中央値6.0日) であった. 結語: GRASIL®は早期穿刺が可能であり, 移植後36か月以上にわたり透析用バスキュラーアクセスとして有用であることが確認された.

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.