Publications by authors named "Nobuyuki Kuwabara"

35 Publications

Delayed Neurologic Sequelae Caused By Carbon Monoxide Poisoning in a Kidney Transplant Recipient.

Exp Clin Transplant 2019 12 11;17(6):849-851. Epub 2019 Oct 11.

From the Deparment of Urology and Osaka City University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.6002/ect.2019.0034DOI Listing
December 2019

Successful pregnancy after in vitro fertilization in an ABO-incompatible kidney transplant recipient receiving rituximab: a case report.

BMC Nephrol 2019 06 6;20(1):206. Epub 2019 Jun 6.

Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

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.
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http://dx.doi.org/10.1186/s12882-019-1396-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554973PMC
June 2019

Pilot Experience with ABO-Incompatible Kidney Transplantation as a Second Transplant.

Urol Int 2019 16;102(4):441-448. Epub 2019 Apr 16.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.1159/000499490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561684PMC
January 2020

Clinical Outcomes of ABO-Incompatible Kidney Transplantation in Patients with End-Stage Kidney Disease due to Diabetes Nephropathy.

Urol Int 2019 10;102(3):341-347. Epub 2019 Jan 10.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.1159/000496029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518853PMC
December 2019

ABO-incompatible kidney transplantation as a renal replacement therapy-A single low-volume center experience in Japan.

PLoS One 2018 31;13(12):e0208638. Epub 2018 Dec 31.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Introduction: Living 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.

Design: A single center propensity score-matched cohort study.

Patients And Methods: We 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.

Results: After 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.

Conclusion: Currently, ABO-IKT may be an acceptable treatment for patients with ESKD even at a low-volume transplant center.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208638PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312268PMC
May 2019

Favorable Outcomes of Elderly ABO-Incompatible Kidney Transplantation-Pilot Single Center Experience.

Urol Int 2018 9;101(4):459-466. Epub 2018 Oct 9.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.1159/000492721DOI Listing
March 2019

Pilot Conversion Study From Mycophenolate Mofetil to Everolimus in Stable ABO-Incompatible Kidney Transplant Recipients: Analysis of 1-Year Follow-Up Data.

Exp Clin Transplant 2019 04 4;17(2):190-195. Epub 2018 Sep 4.

From the Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.6002/ect.2017.0200DOI Listing
April 2019

Successful Kidney Transplantation in a Patient with Unipapillary Kidney.

Urol Int 2019 31;102(2):243-246. Epub 2018 Aug 31.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.1159/000492475DOI Listing
July 2019

Effect of Age on Conversion to Everolimus with Calcineurin Inhibitor Minimization at A Late Post-Transplant Stage.

Urol J 2018 09 26;15(5):266-271. Epub 2018 Sep 26.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Purpose: 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.

Materials And Methods: 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.

Results: 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%].

Conclusion: 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.
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http://dx.doi.org/10.22037/uj.v0i0.4326DOI Listing
September 2018

Isolated V-Lesion in an ABO-Incompatible Kidney Transplant Recipient Receiving Rituximab.

Exp Clin Transplant 2019 10 15;17(5):678-680. Epub 2017 Nov 15.

From the Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

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.
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http://dx.doi.org/10.6002/ect.2017.0062DOI Listing
October 2019

Acute Cellular Rejection in ABO-Incompatible Renal Transplant Recipients Receiving Rituximab Is Associated with Delayed-Onset Neutropenia.

Ann Transplant 2017 Jul 25;22:455-462. Epub 2017 Jul 25.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.

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.
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http://dx.doi.org/10.12659/aot.902236DOI Listing
July 2017

Passenger Lymphocyte Syndrome in the ABO-Incompatible Kidney Transplant Recipient Receiving Rituximab.

Exp Clin Transplant 2019 08 28;17(4):558-560. Epub 2017 Jun 28.

Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan.

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.
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http://dx.doi.org/10.6002/ect.2016.0261DOI Listing
August 2019

ABO-Incompatible Living Kidney Transplant Recipients from Spousal Donors Receiving Rituximab.

Urol Int 2016 13;97(4):457-465. Epub 2016 Oct 13.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.1159/000449014DOI Listing
April 2018

Clinical Outcome of Elderly Kidney Transplant Recipients from Spousal Donors.

Urol Int 2015 27;95(1):99-105. Epub 2015 Jan 27.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.1159/000368324DOI Listing
June 2016

Late-onset neutropenia and acute rejection in ABO-incompatible kidney transplant recipients receiving rituximab and mycophenolate mofetil.

Transpl Immunol 2014 Aug 13;31(2):92-7. Epub 2014 Jun 13.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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 4weeks 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 12months 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.
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http://dx.doi.org/10.1016/j.trim.2014.06.001DOI Listing
August 2014

Conversion of stable ABO-incompatible kidney transplant recipients from mycophenolate mofetil with standard exposure calcineurin inhibitors (CNIs) to everolimus with very low exposure CNIs-a short-term pilot study.

Clin Transplant 2014 Jan 11;28(1):80-7. Epub 2013 Dec 11.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.1111/ctr.12281DOI Listing
January 2014

[Vesicouterine fistula - Youssef syndrome : a case report].

Hinyokika Kiyo 2013 Jan;59(1):27-9

The Department of Urology, Osaka City University Graduate School of Medicine.

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.
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January 2013

Gene Network Analysis in Amygdala following Taste Aversion Learning in Rats.

Neurosci J 2013 23;2013:739764. Epub 2013 May 23.

Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY 40292, USA.

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 explored in silico experiments 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 silico analysis of differentially expressed genes is therefore necessary to manipulate specific phase/stage of CTA to understand the molecular insight.
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http://dx.doi.org/10.1155/2013/739764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437262PMC
August 2015

Chronic kidney disease in patients with ileal conduit urinary diversion.

Exp Ther Med 2012 Dec 11;4(6):962-966. Epub 2012 Sep 11.

Departments of Urology and.

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%), P<0.0001]. 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.
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http://dx.doi.org/10.3892/etm.2012.703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494134PMC
December 2012

Albuminuria-reducing effect of angiotensin II receptor blocker plus hydrochlorothiazide combination therapy in renal transplant recipients.

Exp Ther Med 2012 Jul 11;4(1):105-108. Epub 2012 Apr 11.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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.
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http://dx.doi.org/10.3892/etm.2012.542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460262PMC
July 2012

ABO-incompatible kidney transplantation in elderly patients over 60 years of age.

Int Urol Nephrol 2012 Oct 25;44(5):1563-70. Epub 2012 Jul 25.

Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.

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 (<1:512), the immunosuppressive protocol consisted of a single dose of rituximab (150 mg/m(2)). The patients with high anti-A/B antibody titers (≥1:512) underwent splenectomy and received 2 doses of rituximab. The pretransplant immunosuppressive protocol included B-lymphocyte suppression with 4 weeks of mycophenolate mofetil (0.5 g/day for low-titer protocol and 1 g/day for high-titer protocol).

Results: All 4 patients underwent successful transplantation. At the end of follow-up, their mean serum creatinine was 1.18 mg/dl. No patient experienced antibody-mediated rejection or acute cellular rejection. Late-onset neutropenia occurred in two cases. Two cases experienced cytomegalovirus reactivation by cytomegalovirus antigenemia. In one patient, diffuse hemorrhage required surgical intervention. However, there were no severe complications.

Conclusions: Although a careful evaluation of patients is needed, ABO-incompatible kidney transplantation may become a viable treatment option for elderly patients with end-stage renal disease.
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http://dx.doi.org/10.1007/s11255-012-0231-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444708PMC
October 2012

Conditioned taste aversion dependent regulation of amygdala gene expression.

Physiol Behav 2012 Feb 13;105(4):996-1006. Epub 2011 Nov 13.

Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, United States.

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.
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http://dx.doi.org/10.1016/j.physbeh.2011.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260345PMC
February 2012

Glucose intolerance in renal transplant recipients is associated with increased urinary albumin excretion.

Transpl Immunol 2011 May 2;24(4):241-5. Epub 2011 Mar 2.

Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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 75g 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.
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http://dx.doi.org/10.1016/j.trim.2011.02.001DOI Listing
May 2011

Clinical outcome of ABO-incompatible living unrelated donor kidney transplantation.

Urol Int 2011 25;86(3):307-14. Epub 2011 Feb 25.

Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, Japan.

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.
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http://dx.doi.org/10.1159/000324103DOI Listing
September 2011

Association between chronic kidney disease and small residual urine volumes in patients with benign prostatic hyperplasia.

Nephrology (Carlton) 2011 Mar;16(3):335-9

Departments of Urology Endocrinology, Metabolism and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

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 (<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.

Methods: 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 (PVR < 12 mL, 12 mL ≤ PVR < 50 mL, 50 mL ≤ PVR < 100 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.

Results: The PVR of the patients with CKD was significantly greater than that of the patients without CKD. The group with the normal PVR (group PVR < 12 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.

Conclusion: 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.
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http://dx.doi.org/10.1111/j.1440-1797.2010.01430.xDOI Listing
March 2011

[A case of dedifferentiated liposarcoma of the spermatic cord].

Hinyokika Kiyo 2009 Nov;55(11):733-6

The Department of Urology, Yao Municipal Hospital, Japan.

A 61-year-old man was referred to our department because of painless and stony hard mass beside the left testis. Serum levels of lactate dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin were within normal ranges. The ultrasonography of the mass showed almost homogenous and relatively low intensity echogram. The mass which derived from the left spermatic cord and was partially surrounded by fat-like soft and yellow tissue, was removed with the left testis by usual orchiectomy. Histopathological diagnosis was liposarcoma, whose subtype was dedifferentiated type derived from well differentiated type. Postoperatively, a para-aortic mass, which resembled lymphnode metastasis, was pointed by computed tomographic scan and was removed surgically. However, it was histopathologically diagnosed as neurogenicganglioma irrelevant to liposarcoma. He has been free of disease for about 1 year without any adjuvant therapy.
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November 2009

[A case of primary mucinous adenocarcinoma of the scrotal contents].

Hinyokika Kiyo 2009 Jul;55(7):441-4

The Department of Urology, Yao Municipal Hospital.

A 48-year-old man consulted our hospital complaining of painless swelling of the left scrotal contents that had gradually increased for 5 years. Serum LDH, alpha-fetoprotein and HCG were within normal ranges. The ultrasonography showed heterogeneous echogram including high-echogenic spots and relatively a low-echogenic hydrocele. Left high orchiectomy was performed and the removed tissue was 24 x 16 x 15 cm in size, which had large cystic cavity filled with cloudy and deep-green mucin. Pathological diagnosis was mucinous adenocarcinoma. Postoperatively analyzed serum CEA, CA19-9 and PSA were within normal ranges. Systemic X-ray examinations, such as lung, abdominal and pelvic CT scan, upper GI series and barium enema, did not show any abnormal SOL suggesting carcinoma. Therefore, we diagnosed this case as a primary adenocarcinoma in the scrotal contents. The patient has been observed without any adjuvant therapy since operation, but no signs of recurrence have been identified for one year and six months.
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July 2009

Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy.

Urology 2006 Feb;67(2):440-6

Department of Urology, Osaka City University Medical School, Osaka, Japan.

Objectives: To test whether curcumin has a protective action against interstitial inflammation and the development of renal fibrosis in obstructive nephropathy. We also tested whether inhibition of nuclear factor kappa-B (NF-kappaB) and activator protein-1 (AP-1) by curcumin is involved in these mechanisms.

Methods: Adult male rats underwent unilateral ureteral obstruction. The rats were treated with curcumin (200 mg/kg/day or 800 mg/kg/day), NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC; 200 mg/kg/day), or vehicle by gavage. Sham-operated rats served as controls. Seven days after unilateral ureteral obstruction, the activity of NF-kappaB and AP-1 was examined by electrophoretic mobility shift assay using nuclear protein extracts from the renal cortex. Gene expression of chemokines and pro-fibrotic molecules was determined by real-time reverse transcriptase-polymerase chain reaction. Macrophage infiltration and collagen III accumulation in the cortical interstitium was examined immunohistochemically.

Results: Both curcumin and PDTC significantly attenuated interstitial macrophage influx and renal fibrosis. Ureteral occlusion activated both NF-kappaB and AP-1-DNA binding. Curcumin and PDTC significantly inhibited NF-kappaB activity, but not AP-1. Gene expression of chemokines and pro-fibrotic molecules was upregulated in unilateral ureteral obstruction that was attenuated by either curcumin or PDTC.

Conclusions: Curcumin protected against the renal interstitial inflammation and fibrosis elicited by ureteral occlusion. Inhibition of the NF-kappaB-dependent pathway is at least in part involved in the mechanisms, but AP-1 inhibition is unlikely to be involved in the beneficial effects of curcumin.
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http://dx.doi.org/10.1016/j.urology.2005.09.028DOI Listing
February 2006

Molecular mechanisms and therapeutic strategies of chronic renal injury: the role of nuclear factor kappaB activation in the development of renal fibrosis.

J Pharmacol Sci 2006 Jan 6;100(1):17-21. Epub 2006 Jan 6.

Department of Urology, Osaka City University Medical School, Osaka, Japan.

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 kappaB (NF-kappaB) activity. Similar findings were obtained in chronic tacrolimus nephrotoxicity and obstructive nephropathy. Inhibition of NF-kappaB markedly attenuated renal inflammation and interstitial fibrosis in these models. Furthermore, administration of oral adsorbent (Kremezin) significantly attenuated the increase in renal NF-kappaB 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-kappaB in renal tubular cells. It is suggested that strategy aiming at NF-kappaB inhibition is important to prevent the progression of renal fibrosis.
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http://dx.doi.org/10.1254/jphs.fmj05003x4DOI Listing
January 2006

Chiari anomalies in the human right atrium.

Clin Anat 2006 Sep;19(6):510-6

Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.

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.
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http://dx.doi.org/10.1002/ca.20195DOI Listing
September 2006
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