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OBJECTIVES Here, we report our 1-year follow-up data of stable ABO-incompatible kidney transplant recipients who converted from mycophenolate mofetil plus a standard dose of a calcineurin inhibitor to everolimus plus low exposure to calcineurin inhibitors. MATERIALS AND METHODS Our study included 17 recipients of ABO-incompatible kidney transplant procedures performed at our institution. At baseline and at 3 and 12 months after conversion, graft biopsies were performed to check for acute rejection and C4d deposition. RESULTS Treatment with everolimus was stopped due to adverse events in 8 patients (47.1%). Conversion to everolimus with calcineurin inhibitor minimization did not induce acute rejection or C4d deposition at 3 and 12 months after conversion in ABO-incompatible kidney transplant recipients in whom everolimus was maintained or stopped within 1 year after conversion. CONCLUSIONS Everolimus elicited no acute rejection and no C4d deposition, whether everolimus was maintained or stopped within 1 year after conversion, in ABO-incompatible kidney transplant recipients.

A unipapillary kidney is a very rare anomaly in humans. In this paper, we report on a case of a 47-year-old woman with end-stage kidney disease (ESKD) due to unipapillary kidney, who had been on hemodialysis for 20 years and who had successfully received deceased-donor kidney transplantation. The aim of this report is to present a case of a rare unipapillary kidney patient who underwent kidney transplantation without any urological complications. Our results suggest that kidney transplantation may be an effective renal replacement therapy for patients with ESKD due to unipapillary kidney.

Background: Diabetes nephropathy is one of the most common causes of end-stage kidney disease (ESKD) worldwide. The data are clear that kidney transplantation is superior to remaining on dialysis for patients with diabetes. However, there have been no reports on ABO-incompatible kidney transplantation in patients with ESKD due to diabetes nephropathy. Patients and Methods: We conducted a retrospective, observational study to investigate the clinical outcomes of ABO-incompatible kidney transplantation for patients with pre-existing diabetes nephropathy at our institution from April 2011 to October 2017. A total of 14 recipients were enrolled in this study. Results: All 14 patients underwent successful kidney transplantation. Both overall patient and graft survival rates were 100, 89.9, and 89.9% at 1, 3, and 5 years, respectively. One patient died 20 months after transplantation with a functioning graft due to pancreas cancer. Two of the 14 patients (14.3%) developed biopsy-proven acute cellular rejection during the follow-up period. The median observation period was 32.0 months (range 5–83 months). Conclusion: ABO-incompatible kidney transplantation may be an acceptable renal replacement therapy for ESKD patients with diabetes.

Introduction: The diagnosis of BK virus nephropathy is based on renal biopsy findings, and the diagnosis of presumptive BK virus nephropathy is made by sustained plasma BK virus DNA loads of > 4 log10 copies/ml. However, the BK virus plasma viral load cutoff of 4 log10 copies/ml may underestimate the diagnosis of BK virus nephropathy. In this study, we evaluated the clinical significance of BK viremia in kidney transplant recipients. Patients and Methods: From January 2010 to November 2015, we experienced 8 kidney transplant recipients who developed BK viremia. We retrospectively analyzed these recipients, focusing on the plasma BK viral load at onset of BK viremia, time to BK viremia after transplantation, frequency of BK virus nephropathy, and our treatment for BK viremia. Results: The median plasma BK virus polymerase chain reaction at the diagnosis of BK viremia was 1600 copies/ml (370–9400 copies/ml). The median time to BK viremia after transplantation was 10.9 months (1.4–67.9 months). Three patients were associated with BK virus nephropathy on biopsy. Clearance of BK viremia was observed in all of these cases after intervention. Conclusions: Our study demonstrated that intervention in BK viremia with a viral load of < 4 log10 copies/ml may be needed to prevent the development of graft dysfunction and BK virus nephropathy in kidney transplant recipients. Keywords: BK virus, BK viremia, Kideny transplantation, Mizoribine, Cyclosporine

Passenger lymphocyte syndrome is a rare but important disease in which the donor lymphocytes produce antibodies to the red blood cell antigens of the recipient, causing alloimmune hemolysis. It occurs in ABO blood group-mismatched solid-organ and/or bone marrow transplant. We report a case of passenger lymphocyte syndrome occurring after ABO-incompatible kidney transplant. The recipient received rituximab as a desensitization protocol. On posttransplant day 18, the recipient showed a fall in her hemoglobin levels without identifiable bleeding source and an elevation of total bilirubin. Although hemolytic anemia was suspected, schizocytes on the peripheral smear were not observed. Anti-B-type antibodies were detected, and a diagnosis of passenger lymphocyte syndrome was confirmed. The patient was successfully treated with steroid pulse therapy, an increase of mycophenolate mofetil to 2 g/day, and conversion from cyclosporine to tacrolimus. To our knowledge, this is the first demonstration of passenger lymphocyte syndrome in an ABO-incompatible kidney recipients receiving rituximab.

Background: Despite advances in immunosuppressant medications, improvement in long-term survival for kidney transplant recipients has been more difficult to achieve. In fact, the number of patients with failing grafts who must either return to dialysis or undergo a second transplant is increasing. Second transplantation is associated with reduced mortality rates compared to remaining on dialysis after an initial graft loss. Nowadays, excellent ABO-incompatible kidney transplant outcomes have been achieved. However, there have been no reports on ABO-incompatible kidney transplantation as a second transplant. Patients and Methods: Three patients who received their graft from an ABO-incompatible living donor at our institution as a second transplant were enrolled in this study. We focused on immunosuppressive therapy for second ABO-incompatible kidney transplantation, donor-specific antibody status before the second transplant, patient and graft survivals, and complications. Results: All 3 patients successfully underwent ABO-incompatible kidney transplantation as a second transplant with a follow-up period of 141, 39, and 24 months. Patient and graft survival rates were 100%. Conclusions: ABO-incompatible kidney transplantation may be an acceptable treatment for patients who need a second renal replacement therapy after their initial graft failure.

This study describes our clinical experience of late conversion from antimetabolites with standard exposure calcineurin inhibitors (CNIs) to everolimus with CNI minimization in stable kidney transplant recipients with good graft function.A 1-year retrospective pilot study of 26 kidney recipients converted from antimetabolites with standard exposure CNIs to everolimus with CNI minimization was performed. The recipients enrolled in this study had normal or slightly impaired renal function defined as a serum creatinine value 2.0 mg/dL, and normal or slightly increased albuminuria defined as a urinary albumin excretion rate 100 mg/g creatinine.The median time from transplant to conversion was 39.5 months posttransplant (range, 3-275). Treatment with everolimus was stopped owing to adverse events in 11 patients (42.3%). In the analysis of the patients in whom everolimus was maintained, the mean estimated glomerular filtration rate (eGFR) significantly increased from 50.7 ± 11.9 mL/min/1.73 m(2) at baseline to 53.6 ± 13.9 mL/min/1.73 m(2) at 1 year after conversion. In the patients in whom everolimus was stopped during the observation period, there was no difference in eGFR between baseline and 1 year after conversion.This study demonstrated that, among the patients converted to everolimus at a late stage, there was no deterioration in renal function whether everolimus was maintained or stopped within 1 year after conversion.

Introduction: We summarized our experience with ABO-incompatible living kidney transplant recipients from spousal donors receiving rituximab. Patients and Methods: Between June 2006 and December 2014, 82 patients with end-stage renal disease underwent living donor kidney transplantation at Osaka City University Hospital, of which 23 cases were ABO-incompatible transplantation between spouses with rituximab induction. We analyzed these recipients, focusing on their immunosuppressive protocols, frequency of acute rejections, and patient/graft survivals. Results: Patient and graft survival rates were 100%. The incidence of acute cellular rejection (ACR) was 30.4%. One patient experienced antibody-mediated rejection (AMR) and intractable ACR, 2 had AMR, and 2 had intractable ACR episodes that were treated using thymoglobulin. Conclusions: This study demonstrated that ABO-incompatible kidney transplantation between spouses using rituximab is a radical but effective treatment for end-stage renal disease. However, this procedure could be immunologically high risk due to ABO-incompatibility and poor histocompatibility.

Background Successful pregnancy outcomes after in vitro fertilization in kidney transplant recipients have been reported, but few cases of successful pregnancy after ABO-incompatible kidney transplantation have been described. Herein, we report on a successful pregnancy after in vitro fertilization in an ABO-incompatible kidney transplant recipient with rituximab, focusing on the changes in immunity. Case presentation A 35-year-old woman with end-stage kidney disease caused by IgA nephropathy was referred for kidney transplantation and successfully underwent an ABO-incompatible living-donor kidney transplant using rituximab from her 66-year-old father at the age of 36. Because she and her husband desired childbearing, they received fertility treatments, and embryo cryopreservation was performed before transplantation. Two years after the transplant, she desired pregnancy. Although immunoglobulin levels such as IgG, IgA and IgM had recovered to almost normal range, the peripheral CD19+ cells and CD20+ cells remained depleted. At 6 months after conversion from mycophenolate mofetil to azathioprine, frozen embryo transfer was performed during the hormone replacement cycle. At 37 weeks and 4 days gestation, a healthy baby girl weighing 2220 g was delivered by cesarean section for arrest of labor. There were no complications in both the recipient and her baby during the perinatal period. At 5 years after the transplant, the recipient has had no major complications including rejection or infection. Conclusions It is possible for women receiving ABO-incompatible kidney transplantation with rituximab to successfully become pregnant and deliver a heathy baby after in vitro fertilization, if IgG levels recover to normal range despite depleted peripheral blood B cells.

The purpose of this study was to identify the risk factors for everolimus discontinuation in kidney transplant recipients converted to everolimus with calcineurin inhibitor (CNI) minimization at a late post-transplant stage.An observational retrospective cohort study was conducted on a total of 38 recipients of kidney transplantation at our institution from June 2012 to March 2015 who were converted from antimetabolites to everolimus at a late post-transplant stage and followed for 1 year. We divided the patients into two groups to evaluate the factors affecting everolimus discontinuation after conversion: everolimus continuation group (n = 23), patients in whom everolimus maintained, and everolimus discontinuation group (n = 15), patients in whom everolimus were stopped within 1 year after conversion.Age at conversion was significantly older in the everolimus discontinuation group compared to the everolimus continuation group (57.9 ± 12.0 years in the everolimus discontinuation group vs 45.7 ± 11.2 years in the everolimus continuous group; P = .0062). Multivariate cox proportional hazard regression analysis revealed that age at conversion significantly correlated with everolimus discontinuation (P = .012). Receiver operating characteristic curve of age at conversion showed that the cut-off value was 55 years old for the everolimus discontinuation group [area under curve 0.804, 95% confidence interval (0.654-0.954), sensitivity 86.7%, specificity 65.2%].Our results indicated that late conversion to everolimus with CNI minimization in elderly recipients older than 55 years of age may be associated with more frequent adverse events and discontinuations.

Background: The growth in the end-stage kidney disease (ESKD) population has been predominantly in the older adult population. In Japan, ABO-incompatible kidney transplantation has become an acceptable treatment option. However, few studies have been conducted on elderly ABO-incompatible kidney transplantation. Patients and Methods: Seventeen patients aged 60 years and older who received their grafts from ABO-incompatible living donors at our institution between December 2006 and September 2016 were enrolled in this study, and the outcome of these recipients was evaluated. Results: All 17 patients underwent successful kidney transplantation. Both overall patient and graft survival rates were 100, 100, and 83.3% at posttransplant 1, 3, and 5 years respectively. Six of the 17 patients (35.3%) had an episode of biopsy-proven acute cellular rejection. Two patients who developed steroid- and deoxyspergualin-resistant acute rejection required anti-human thymocyte immunoglobulin. Conclusion: ABO-incompatible kidney transplantation may be an effective radical renal replacement therapy for elderly patients with ESKD, although it could be a high-risk procedure.

Introduction: Patients aged 60 years and older stand for the fastest growing group of patients with end-stage renal disease worldwide, and the need for kidney transplants among this population is rising. In Japan, living donor kidney transplantation is mainly performed to deal with the severe shortage of deceased donors, and the number of spousal transplants is currently increasing. Patients and Methods: A total of 164 patients with ESRD underwent living donor kidney transplantation at our institution, of whom 21 patients aged 60 years and older had spousal kidney transplantation. ABO-incompatible kidney transplantation was performed in 5 of the 21 cases. We analyzed these recipients. Results: Patient and graft survival rates were 100%. The incidence of acute rejection was 23.8%. Eight patients experienced cytomegalovirus viremia, two patients experienced Pneumocystis jiroveci infection, and one experienced bacterial pneumonia. Two patients developed cancers and underwent curative operation after transplantation. Conclusions: Elderly kidney transplantation from spousal donors is associated with age-related immune dysfunction, which may develop infections and malignancies and could be immunologically high risk due to the high rate of ABO-incompatibility and poor histocompatibility. An effort to minimize the adverse effect of immunosuppression and to reduce the risk of acute rejection may be needed for an excellent long-term outcome.

We report an ABO-incompatible kidney transplant performed on a 69-year-old female patient, whose donor was her 69-year-old husband. The patient received an immunosuppressive protocol using rituximab without splenectomy. Renal biopsy was done on posttransplant day 8 due to poor early graft function, and an isolated v-lesion was found, which responded to steroid pulse therapy and gusperimus hydrochloride administration. Our results indicate that isolated v-lesions can occur in ABO-incompatible kidney transplant recipients receiving rituximab and that this finding should be treated as acute rejection. To our knowledge, this is the first report of an isolated v-lesion in an ABO-incompatible kidney transplant recipient who had been administered rituximab.

BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral blood and increases the levels of proinflammatory cytokines associated with regulatory B cell depletion. Previous reports showed that B cell-related cytokine release after administration of rituximab may induce acute cellular rejection (ACR) and delayed-onset neutropenia. The present study was conducted to investigate the correlation between acute rejection and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006 to July 2015, 47 patients with chronic renal failure received ABO-incompatible renal transplant with rituximab induction at Osaka City University Hospital. All 47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and administration of rituximab, and their transplants were carried out successfully. We investigated the correlation between ACR and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%) experienced ACR (group A), and 33 recipients did not develop ACR (group B). The frequency of delayed-onset neutropenia was higher in group A than in group B (p=0.0503). Multivariate logistic regression analysis revealed that the frequency of ACR correlated significantly with the prevalence of delayed-onset neutropenia. CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant recipients receiving rituximab was associated with delayed-onset neutropenia.

Background A recent report has demonstrated that as with mycophenolate mofetil (MMF), everolimus is capable of inhibiting human B-lymphocyte function and activation including B-lymphocyte proliferation, apoptosis, and immunoglobulin production in vitro. Everolimus may therefore be used as an immunosuppressant in ABO-incompatible kidney transplantation. Methods A three-month pilot study was performed to examine the efficacy and safety of conversion of stable ABO-incompatible kidney transplant recipients from MMF with standard exposure calcineurin inhibitors (CNIs) to everolimus with very low exposure CNIs. Sixteen recipients were enrolled in the study. The patients without acute rejection by graft biopsy were switched from MMF to everolimus with CNI minimization. At three months after conversion, graft biopsies were performed to check for acute rejection and C4d deposition. Results Conversion to everolimus with CNI minimization for three months did not induce acute rejection and C4d deposition in all of the ABO-incompatible kidney transplant recipients. A slight elevation of anti-A/B antibody titer occurred in our present study. Everolimus was associated with hyperlipidemia and edema. Conclusions These results demonstrated that short-term conversion from MMF to everolimus after one yr post-transplant may be a safe and effective alternate for ABO-incompatible kidney transplant recipients requiring temporary discontinuation of MMF.

IntroductionLiving donor kidney transplantation is preferable to deceased donor transplantation due to its superior long-term patient and graft survivals. However, ABO blood group incompatibility is a major barrier to living donor kidney transplantation. ABO-incompatible kidney transplantation has been performed in Japan since the late 1980's, but it is still globally uncommon. The objective of this study is to compare the clinical outcomes of ABO-incompatible kidney transplantation (ABO-IKT) with that of ABO-compatible kidney transplantation (ABO-CKT) at an institution where only about two kidney transplants are performed a month on average.DesignA single center propensity score-matched cohort study.Patients and methodsWe retrospectively collected and analyzed the data of 240 patients with end-stage kidney disease (ESKD) who underwent living donor kidney transplantation at Osaka City University Hospital from January 1999 to December 2016, of which 66 patients were ABO-IKT. The remaining 174 patients who underwent ABO-CKT were studied as the control group, and the clinical outcomes of ABO-IKT and ABO-CKT recipients were compared based on propensity score matching.ResultsAfter propensity score matching, there were no significant differences in both patient survival and death-censored graft survival rates between the ABO-IKT and ABO-CKT groups. Moreover, there were no significant differences in estimated glomerular filtration rate as well as frequency of acute cellular rejection, antibody-mediated rejection, infectious adverse events, malignancies, and post-operative bleeding between the two groups.ConclusionCurrently, ABO-IKT may be an acceptable treatment for patients with ESKD even at a low-volume transplant center.

While renal dysfunction is often observed in patients following urinary diversion due to bladder cancer, there have been few studies on this subject. A cross-sectional study was performed on the renal function of ileal conduit urinary diversion patients and the prevalence and risk factors for chronic kidney disease (CKD) were examined. Patients with ileal conduit urinary diversion (n=102), who were being followed-up as outpatients and who were in stable condition, as well as age- and gender-matched healthy control subjects (n=63) were selected for this study. The prevalence of CKD was compared between the patients and healthy subjects. Next, the clinical factors associated with the presence of CKD were investigated in the patients with ileal conduit diversion using logistic regression analysis. The prevalence of CKD was significantly higher in the patients with ileal conduit diversion compared with the healthy subjects [60 patients (58.8%) vs. 11 healthy subjects (17.5%), P0.0001]. The mean decrease in the estimated glomerular filtration rate per year of the patients with urinary diversion was 0.95±2.0 ml/min/1.73 m(2). Multiple logistic regression analysis revealed that the independent and significant factors associated with the presence of CKD were older age and the presence of hypertension, urolithiasis and a past history of hydronephrosis. In conclusion, an increased prevalence of CKD was revealed in the patients with ileal conduit urinary diversion, suggesting the need for better management of hypertension, urolithiasis and hydronephrosis following surgery.

Introduction Patients aged 60 years and older represent the fastest-growing population with end-stage renal disease worldwide, and the need for a kidney transplant among this population is increasing. Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved, and the rates of graft survival in these patients are currently similar to those in recipients of ABO-compatible grafts. However, the outcomes of ABO-incompatible kidney transplantation in elderly patients over 60 years of age have not been well studied yet. Patients and methods We studied 4 elderly kidney transplant patients who received their grafts from ABO-incompatible living donors at our institution between December 2006 and December 2011, focusing on the immunosuppressive protocols, complications and graft survivals. The mean observation period was 21.5 months (range, 8 months to 62 months). Our immunosuppressive protocols were as follows: to remove the anti-A/B antibodies, the patients underwent 4–8 sessions of double-filtration plasmapheresis and/or plasma exchange prior to kidney transplantation until the anti-A/B titers were less than 1:16. For the patients with low anti-A/B titers (

Background The adverse effects of tacrolimus are known to play major roles in posttransplantation diabetes mellitus (PTDM). In the present study, we investigated the effects of conversion from a twice-daily (Tac BID) to a once-daily prolonged release of tacrolimus formulation (Tac OD) on glucose metabolism in stable kidney transplant recipients. Patients and Methods In this prospective study, 26 patients converted from Tac BID to the same milligram-milligram daily dose of Tac OD were examined for the effects on renal function, drug trough levels, and glucose metabolism over a 4-week period. Results Conversion from Tac BID to Tac OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough levels, but no significant changes in renal function. At 4 weeks after conversion, a homeostasis model assessment of β-cell function, and hemoglobin A1c (HbA1c) decreased significantly. Conclusions This study demonstrated a significant reduction in tacrolimus trough levels after switching from Tac BID to Tac OD, which increased insulin secretion and decreased HbA1c, suggesting that it may decrease the frequency of PTDM among stable renal transplant recipients.

Introduction Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved; the rates of graft survival among these patients are currently similar to those of recipients of ABO-compatible grafts. Our single-center experience describing the immunosuppressive protocols, complications, and grafts survivals is documented in this study. Patients and Methods Among 123 patients with end-stage renal disease who underwent living donor kidney transplantation between January 1999 and December 2010, 25 cases were ABO-incompatible grafts. All of these patients were followed until August 2011. Analyzing these patients, we focused on their immunosuppressive protocols, complications, and graft survivals. Results Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and an intractable acute cellular rejection episode, 1 patient an antibody-mediated rejection, and 6 patients had acute cellular rejection episodes. However, there were no severe complications. Conclusion Although ABO-incompatible kidney transplantation is a high-risk procedure, a short-term graft survival rate of 100% may be expected due to recent significant improvements in desensitization and recipient management.

Aim: It has been well described that large residual urine volumes (≥300 mL) affect renal function in advanced benign prostatic hyperplasia (BPH). However, it is not clear whether small residual urine volumes (

Background: ABO-incompatible living unrelated donor kidney transplantation is an immunologically high-risk procedure, but few reports have been made on the outcomes of these transplants. Patients and Methods: We analyzed 12 kidney transplants using ABO-incompatible living-unrelated donors performed at our institution between January 1999 and December 2007, focusing on the immunosuppressive protocols, complications and graft survivals. Results: Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and intractable acute cellular rejection, one had antibody-mediated rejection and one had acute cellular rejection, but their grafts survived after intensive immunosuppressive treatment. There were no severe complications among the recipients. Conclusions: In ABO-incompatible living unrelated donor kidney transplantation, severe rejections may occur due to ABO incompatibility and poor histocompatibility. Therefore, appropriate desensitization, immunosuppression and recipient care are needed for a successful transplant. Recent significant improvements in outcomes indicate that it has become a viable treatment option, given the lack of available donor organs.

Tubulointerstitial fibrosis is a common feature of many progressive renal diseases and is a main determinant that leads to an irreversible loss of renal function. In chronic cyclosporin A nephrotoxicity, we previously reported that inflammatory responses such as macrophage infiltration preceded interstitial fibrosis. This inflammation was accompanied by an elevation in renal nuclear factor κB (NF-κB) activity. Similar findings were obtained in chronic tacrolimus nephrotoxicity and obstructive nephropathy. Inhibition of NF-κB markedly attenuated renal inflammation and interstitial fibrosis in these models. Furthermore, administration of oral adsorbent (Kremezin®) significantly attenuated the increase in renal NF-κB activity and concomitantly reduced interstitial inflammation and renal fibrosis in chronic renal failure rats. Elimination of indoxyl sulfate by this adsorbent is likely involved in this mechanism since it is known that indoxyl sulfate activates NF-κB in renal tubular cells. It is suggested that strategy aiming at NF-κB inhibition is important to prevent the progression of renal fibrosis. Keywords:: nuclear factor κB, renal fibrosis, nephrotoxicity, unilateral ureteral obstruction, oral adsorbent

Chiari anomalies in the human right atrium ostensibly are encountered rarely. There is only sporadic mention in the literature of these fenestrated, net-like valves of the inferior vena cava, coronary sinus, or various strands connecting these with other right atrial structures. The effects of such structural anomalies on heart function are unknown. We report here gross observations of the right atrial net from among 213 cadavers, 38 autopsied, and 11 fetal hearts. Histological and ultrastructural examination of inferior vena cava and coronary sinus valves demonstrated that only the anomalous coronary sinus valves contained cardiac muscle. Chiari anomalies typically have referred to perforations or tissue strands related to the inferior vena cava valve and possibly the coronary sinus valve. The anomaly commonly is cited as occurring in 2% of individuals, although there has been no study to support this. We observed Chiari malformations in 13.6% of the 213 cadaver hearts, and 10.5% of the autopsied hearts examined. Of these malformations, the coronary sinus valve was fenestrated most frequently. We propose the term "right atrial net" for "Chiari net," for anomalies involving valves of the inferior vena cava and coronary sinus, and strands within the right atrium connecting these valves with the crista terminalis, right atrial wall, or interatrial septum.

Background. It has been shown that the transcription factors activator protein (AP)-1 and nuclear factor (NF)-κB play a pivotal role in various renal diseases. We aimed to study their activations in chronic cyclosporine A (CsA) nephrotoxicity and evaluate the effect of magnesium (Mg) supplementation

Bilateral ganglionic masses, likely representing fused superior and middle cervical sympathetic ganglia, were found in the mid-neck region of a cadaver during routine dissection. The displacement of the superior cervical ganglion from its normal location is a striking anomaly that does not appear to have been reported earlier. This observation may be clinically relevant for avoiding misdiagnosis of such masses as Schwannomas or other tumors. In addition, in cases where the superior cervical ganglion is absent from its usual location, it should be sought in the mid-neck region.

The present study was conducted to elucidate the role of oxidative stress and nuclear factor-kappaB (NF-kappaB) in the beneficial effects of angiotensin receptor blockade on obstructive nephropathy. Unilateral ureteral occlusion in rats elicited tubulo-interstitial fibrosis with concomitant macrophage infiltration and increased expression of monocyte chemoattractant protein-1. These changes were accompanied by an induction of renal cortical lipid peroxidation and activation of NF-kappaB. Both an AT(1) antagonist, candesartan, and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated these changes and to a similar extent. These results suggest that the beneficial effects of angiotensin blockade are mediated by the inhibition of oxidative stress and subsequent NF-kappaB activation in obstructive nephropathy.

Introduction Using rituximab, we have performed successful ABO-incompatible kidney transplantations in recipients without splenectomy as well as in those with high pretransplant anti-A/B antibody titers. A common and increasingly recognized toxicity of rituximab is late-onset neutropenia (LON), defined as unexplained grades III to IV neutropenia occurring at least 4 weeks after the last dose of rituximab in the absence of an alternative explanation. Patients and methods Between May 2006 and December 2011, 25 patients who received rituximab underwent successful ABO-incompatible kidney transplantation and were enrolled as the subjects in this study. The incidence rate and clinical features of LON as well as the relationship between LON and acute rejection in these patients were studied. Results Twelve recipients (48%) experienced LON 2 to 12 months after transplantation. Five of the 12 patients (41.6%) who developed LON had an episode of biopsy-confirmed acute cellular rejection, as compared with one of the 13 patients (7.7%) who did not develop LON. Moreover, 3 patients who experienced LON developed steroid and deoxyspergualin-resistant acute cellular rejection requiring OKT-3 administration. Conclusions The frequency of acute cellular rejection was higher in ABO-incompatible kidney transplant recipients with LON than in those without LON. Our findings suggested that these recipients who developed LON after rituximab administration may be at an increased risk for acute cellular rejection.

Axonal projections were labeled using a combination of tract-tracing and intracellular staining to examine the connection between the auditory thalamus and tectum. We report descending projections from the medial and dorsal divisions of the medial geniculate body to the external nucleus of the ipsilateral inferior colliculus and lower brainstem of the gerbil. These were studied in quasi-parasagittal brain slice preparations containing auditory thalamus, tectum and brainstem. Slices were cut in a curved, roughly parasagittal plane from the level of the thalamus to the brainstem. When properly cut, a single thick slice included most of the ipsilateral auditory cell groups and pathways at these levels. The geniculo-collicular projections were revealed after extracellular injections of Biocytin and rhodamine-conjugated biotinylated dextran amine in the medial geniculate body were applied to these slices. Furthermore, cells in the medial geniculate body that had been retrogradely prelabeled with a fluorescent tracer, Fluoro-Gold, injected in the inferior colliculus were intracellularly labeled to confirm the presence of the descending axons. In these preparations, single cells with descending axons were traced through their entire extent to their terminals in the inferior colliculus. Our results clearly demonstrate the geniculo-collicular descending projection and suggest a thalamo-tectal feedback loop.

Local collateral projections from the medial superior olivary nucleus in the gerbil auditory brainstem were examined to study the possible communication of this nucleus with periolivary cell groups. The projections were investigated using intracellular and extracellular labeling with Biocytin in the medial superior olive (MSO) in brainstem tissue slices. Collateral axons were found to branch from the main axons of the central cells of the MSO as the latter passed through a dorsally neighboring periolivary nucleus, the superior paraolivary nucleus (SPN), toward the ipsilateral inferior colliculus (IC), their traditionally accepted target. Bouton-like endings and en passant varicosities of these collaterals appeared to contact the somata and proximal dendrites of cells within the SPN. Furthermore, close observation revealed that these collaterals terminate on at least two types of SPN cells. Intracellular labeling of the collateral axons of the MSO neurons combined with retrograde prelabeling of their target cells, however, revealed that the collaterals selectively contact the cells of the SPN that project to the ipsilateral IC. A link between the MSO and SPN has not been reported previously. This connection is of interest since SPN cells themselves project either to the cochlear nuclei (CN) or the IC. The MSO-SPN projection identified here raises the possibility that the latter may serve as an ancillary channel to convey MSO information to the IC.

Recent studies have indicated that angiotensinogen (AGT) is also locally produced in the kidney and that urinary AGT is a marker of local renal renin-angiotensin system activation. Because urinary AGT levels are significantly higher in patients with chronic kidney disease (CKD) than in patients without CKD and correlate with urinary albumin and other levels, urinary AGT is increasingly recognized as a marker for CKD monitoring, prognosis, and treatment. In this study, we investigated urinary AGT levels in renal transplant recipients.Among the patients who were treated as outpatients at the Department of Urology of Osaka City University Hospital from March 2012 to April 2013, 146 stable renal transplant recipients and 50 donors who gave informed consent were studied. Urinary AGT and creatinine (Cr) levels were measured. The urinary AGT-to-Cr ratio was calculated, and its correlation with clinical parameters was examined.The urinary AGT-to-Cr ratio of the renal transplant recipients was significantly higher than that of the renal transplant donors (P = .0143). Furthermore, the urinary AGT-to-Cr ratio had a significantly positive correlation with the urinary albumin-to-Cr ratio (ACR; r = 0.39, P.0001), while on the other hand, it had a significantly negative correlation with estimated glomerular filtration rate (eGFR; r = -0.31, P = .0002). Multiple linear regression analysis of factors associated with eGFR showed that urinary AGT was a significant and independent factor after adjusting for age, sex, and ACR.Our results indicated that urinary AGT levels were elevated in renal transplant recipients. In addition, urinary AGT significantly correlated with renal function and degree of albuminuria.

Introduction The adverse effects of tacrolimus are known to play major roles in new-onset diabetes after transplantation. The purpose of this study was to investigate the effects of conversion from a twice-daily tacrolimus (Tac-BID) to a once-daily tacrolimus (Tac-OD) on glucose metabolism in stable kidney transplant recipients. Patients and methods Twenty-six patients were converted from Tac-BID to Tac-OD on a 1:1 mg basis and examined for its effects on glucose metabolism. Unless rejection or tacrolimus toxicity was suspected, we did not perform dose adjustments of Tac-OD or reconversion to Tac-BID until 4 weeks after conversion. Subsequent dose adjustments were allowed to maintain tacrolimus target trough concentration within the. Changes in clinical parameters were compared between baseline and 24 weeks after conversion. Results Conversion from Tac-BID to Tac-OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough level at 4 weeks after conversion. Because dose adjustments were performed, the trough level did not differ significantly between baseline and 24 weeks after conversion. At 4 and 24 weeks after conversion, the homeostasis model assessment of pancreas β-cell function (HOMA-β) increased significantly. Conclusions Although there was no change in tacrolimus trough level between baseline and 24 weeks after transplantation, HOMA-β at 24 weeks after conversion was significantly higher than that at baseline. These results indicated that conversion from Tac-BID to Tac-OD may improve pancreas β-cell function in kidney transplant recipients.

A 38-year-old woman was referred to our hospital with a chief complaint of cyclic hematuria and amenorrhea after Caesarean section. Magnetic resonance imaging showed vesicouterine fistula. The patient was treated with luteinzing hormone-releasing hormone analog to stop menstruation for six months. We performed transperitoneal closure of the vesicouterine fistula. Normal menstruation resumed after 4 months, and the symptoms disappeared. This case was considered Youssef syndrome (cyclic hematuria without vasinal amenorrhea or urinary incontinence). We discuss the cause of this syndrome.

Conditioned taste aversion (CTA) is an adaptive behavior that benefits survival of animals including humans and also serves as a powerful model to study the neural mechanisms of learning. Memory formation is a necessary component of CTA learning and involves neural processing and regulation of gene expression in the amygdala. Many studies have been focused on the identification of intracellular signaling cascades involved in CTA, but not late responsive genes underlying the long-lasting behavioral plasticity. In this study, we exploredin silicoexperiments to identify persistent changes in gene expression associated with CTA in rats. We used oligonucleotide microarrays to identify 248 genes in the amygdala regulated by CTA. Pathway Studio and IPA software analyses showed that the differentially expressed genes in the amygdala fall in diverse functional categories such as behavior, psychological disorders, nervous system development and function, and cell-to-cell signaling. Conditioned taste aversion is a complex behavioral trait which involves association of visceral and taste inputs, consolidation of taste and visceral information, memory formation, retrieval of stored information, and extinction phase.In silicoanalysis of differentially expressed genes is therefore necessary to manipulate specific phase/stage of CTA to understand the molecular insight.

Background Although new-onset diabetes after transplantation has been demonstrated to have a significant negative impact on allograft and patient survival, the role of glucose intolerance (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT], as asymptomatic hyperglycemia and borderline diabetes, has not been identified in renal transplant recipients. Methods We enrolled 32 renal transplant recipients (at least 1year after transplantation) without prior evidence of diabetes at our institution in this study. Transplant recipients were divided into 2 groups (normal glucose tolerance group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose. Glucose intolerance included IFG, IGT, and IFG/IGT. Normal glucose tolerance was detected in 19 patients, and glucose intolerance in 13: had 6 IGT, 2 IFG, and 5 IGT/IFG. Bilateral brachial-ankle pulse-wave velocity (baPWV) and intimal-media thickness (IMT) measured as markers of atherosclerosis were compared between the 2 groups. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic β-cell function evaluated by the homeostasis model assessment of β-cell function and insulinogenic index. Results The patients in the glucose intolerance group showed significantly greater baPWV and IMT than those in the normal glucose tolerance group. HOMA-R in the glucose intolerance patients was significantly higher than in the normal glucose tolerance patients. Linear regression analysis showed the increased IMT in the renal transplant recipients to be significantly correlated with HOMA-R. Conclusions Renal transplant recipients with glucose intolerance had increased IMT and baPWV, suggesting that glucose intolerance in renal transplant recipients may induce atherosclerosis and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

Background Several reports have suggested an association between hepatitis C virus (HCV) infection and new-onset diabetes after transplantation (NODAT). NODAT is a common complication after renal transplantation, and it has been associated with increased long-term morbidity and mortality. HCV-positive recipients may have abnormal glucose metabolism, even though NODAT has never been previously diagnosed. The aim of this study was to analyze the pathogenic factors responsible for glucose metabolism in a series of HCV-positive renal transplant recipients. Methods The study population comprised 16 renal transplant patients who received their grafts from deceased or living donors with anti-HCV antibodies. HCV-negative transplant recipients were individually matched with these HCV-positive recipients by year of transplantation, sex, age, serum creatinine levels, and type of calcineurin inhibitors. None of the patients had been diagnosed with diabetes. Insulin secretion and insulin resistance were determined by a 75-g oral glucose tolerance test (OGTT) and compared between the 2 groups. Categories of glucose tolerance were defined according to World Health Organization criteria. Results Glucose intolerance (impaired fasting glucose, impaired glucose tolerance, diabetes mellitus) as assessed by OGTT was detected in 7 of the HCV-positive recipients (43.8%) and 3 of the HCV-negative recipients. The homeostasis model assessment of insulin resistance was greater in the HCV-positive recipients than in the HCV-negative recipients. The homeostasis model assessment of β-cell function was higher in the HCV-positive recipients than in the HCV-negative recipients. Conclusions The frequency of glucose intolerance tended to be higher in HCV-positive recipients. Furthermore, insulin resistance was greater and insulin secretion higher in HCV-positive recipients, which indicated that the increase in insulin secretion compensated for insulin resistance observed in these patients. However, HCV-positive renal transplant recipients may ultimately develop NODAT as this compensation diminishes with time.

In recent years, the combined use of angiotensin II receptor blockers (ARBs) and low-dose diuretics has become clinically possible. Moreover, the GUARD and J-CORE studies have confirmed that the addition of low-dose diuretics to renin-angiotensin system inhibitors reduces albuminuria. In this study, we investigated the clinical effects of a combination drug containing an ARB and a low-dose diuretic in renal transplant recipients. A total of 13 renal transplant recipients who were receiving the maximum dose of the ARB and presenting with microalbuminuria [urine albumin-creatinine ratio (ACR) of 30–300 mg/g-Cre] were converted to a single pill combination drug containing the same amount of the ARB and 12.5 mg of hydrochlorothiazide (HCTZ) and an intervention study of a crossover trial design was conducted. The clinical parameters were measured at baseline, 3 months after ARB/HCTZ conversion and 3 months after reverting to the ARB and the resulting data were compared. Serum creatinine (S-Cre) and uric acid (UA) levels at 3 months after conversion were significantly higher than those at baseline. The levels of the estimated glomerular filtration rate (eGFR) and ACR at 3 months were significantly lower than those at baseline. S-Cre and UA levels at 3 months after reversion were significantly lower than those at 3 months after conversion. The eGFR and levels of ACR and UA at 3 months after ARB reversion were significantly higher than those at 3 months after conversion. The results of this preliminary study suggest that the combination drug containing an ARB and low-dose diuretic was effective for reducing microalbuminuria in renal transplant recipients. In the future, larger cohort studies are needed to confirm these findings.

The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified “behavior” as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning.

Objective New-onset diabetes mellitus after transplantation (NODAT) is a common and serious complication of renal transplantation, and its incidence is known to be increased by immunosuppressive therapy. It has been reported that urinary albumin excretion is a potent predictor of NODAT. This study was conducted to investigate the relationship between glucose intolerance and urinary albumin excretion in renal transplant recipients. Methods A cross-sectional study of 101 renal transplant recipients without prior evidence of diabetes was conducted. All patients underwent an oral glucose tolerance test with 75 g of glucose. Results The patients with glucose intolerance had a significantly greater urinary albumin excretion than those with normal glucose tolerance. Multivariate logistic regression analysis revealed that the increase of urinary albumin excretion correlated significantly with the homeostasis model assessment of insulin resistance and systolic pressure. Conclusion These results indicated that glucose intolerance is associated with increased albuminuria in renal transplant recipients. The rise in insulin resistance and systolic pressure may contribute to the increase of urinary albumin excretion in renal transplant recipients.

It has been well described that large residual urine volumes (≥300 mL) affect renal function in advanced benign prostatic hyperplasia (BPH). However, it is not clear whether small residual urine volumes (100 mL) are related to renal function. The present study was performed to examine the association between chronic kidney disease (CKD) and the post-void residual urine volume (PVR) in BPH patients.A cross-sectional study was performed in 160 consecutive BPH patients with PVR of less than 100 mL. We first determined the stage of CKD and compared the PVR in subjects with/without CKD. Next, we divided the subjects into three groups according to the extent of PVR (PVR12 mL, 12 mL ≤ PVR50 mL, 50 mL ≤ PVR100 mL) and compared the estimated glomerular filtration rate (eGFR) among these groups. Moreover, risk factors associated with CKD, including the presence of post-void residual urine, were explored by multiple logistic regression analysis.The PVR of the patients with CKD was significantly greater than that of the patients without CKD. The group with the normal PVR (group PVR12 mL) had a significantly higher eGFR compared with the other two groups. Multivariate analysis demonstrated that the presence of post-void residual urine (PVR ≥ 12 mL) was a significant and independent risk factor associated with the presence of CKD.In BPH patients, the PVR of the patients with CKD was significantly greater than that of the patients without CKD and the presence of post-void residual urine (PVR ≥ 12 mL) was independently associated with CKD, indicating a close association between CKD and small residual urine volumes.

Background A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established. Methods We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m2) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6–12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab. Results Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients. Conclusions These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation.