Shunji Nishide

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

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.

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

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.

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

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.

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

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.

Successful Kidney Transplantation in a Patient with Unipapillary Kidney

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.

Experience of lymphangiography as a therapeutic tool for lymphatic leakage after kidney transplantation

INTRODUCTION Lymphatic leakage after kidney transplantation is a relatively frequent complication but sometimes resistant to treatment, and there is no fixed treatment algorithm. The effectiveness of therapeutic lymphangiography for postoperative lymphatic or chyle leakage has been reported, but few reports are available regarding patients who have undergone kidney transplantation. In this study, we report our experience with lymphangiography as a therapeutic tool for lymphatic leakage after kidney transplantation. PATIENTS AND METHODS Intranodal lymphangiography for lymphatic leakage was performed in 4 patients (3 male, 1 female; age range, 38 to 70 years old) after living kidney transplantation at the Osaka City University Hospital in Japan. The amount of drainage before lymphangiography was 169 to 361 mL/day. The procedure for intranodal lymphangiography was as follows: the inguinal lymph node was punctured under ultrasound guidance, and the tip of the needle was instilled at the junction between the cortex and the hilum, after which Lipiodol was slowly and manually injected. RESULTS Lymphangiography was technically successful in 3 out of the 4 patients. In all successful cases, the amount of drainage decreased and leakage finally stopped without additional therapy such as sclerotherapy or fenestration. In 2 cases, we were able to directly detect the leakage site using lymphangiography. The time between lymphangiography and leakage resolution ranged from 8 to 13 days. There were neither complications of lymphangiography nor recurrence of lymphatic leakage in the successful cases. CONCLUSIONS Intranodal lymphangiography may be not only a diagnostic tool but also an effective, minimally-invasive, and safe method for treatment of lymphatic leakage resistant to drainage after kidney transplantation.

Late Conversion to Everolimus with Calcineurin Inhibitor Minimization in Stable Kidney Transplant Recipients - Analysis of Factors Affecting ΔeGFR

Background Immunosuppressive regimens that minimize exposure to calcineurin inhibitors (CNIs) following kidney transplantation have been widely investigated in order to reduce the burden of CNI-related complications. Recent trials have focused on the use of everolimus to facilitate CNI withdrawal or minimization. Previous studies had shown that late conversion to everolimus had no overall renal benefit. However, late conversion of kidney transplant recipients to everolimus has demonstrated renal improvement in patients with a baseline estimated glomerular filtration rate (eGFR) of above 50 ml/min/1.73m2 or in patients who remained on everolimus medication. The aim of this study is to analyze the factors affecting graft function after late conversion to everolimus with CNI minimization in kidney transplant recipients. Patients and Methods A 1-year retrospective pilot study of 56 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 (S-Cr) value<2.0 mg/dl, and normal or slightly increased albuminuria defined as a urinary albumin excretion rate <100 mg/g Cr. For the assessment of graft function, we used &Dgr;eGFR according to the formula &Dgr;eGFR=(eGFR at 12 months after conversion)-(eGFR at conversion). We evaluated the relationship between&Dgr;eGFR and clinical parameters in kidney transplant recipients enrolled in this study. Results The average time from transplant to conversion was 42.9±44.1 months, and treatment with everolimus was stopped due to adverse events in 17 patients (30.3%). &Dgr;eGFR was significantly higher in patients who remained on everolimus than in those who discontinued everolimus medication. Univariate linear regression analysis revealed that &Dgr;eGFR correlated negatively with urinary albumin excretion (R=0.479, p=0.000216) and kidney age (donor age at transplantation+time from transplantation to conversion)(R=0.275, p=0.048). Multivariate linear regression analysis indicated that urinary albumin excretion and everolimus continuation were independently associated with &Dgr;eGFR. Conclusion Our results suggested that late conversion of kidney transplant recipients to everolimus with CNI minimization may lead to improvement in graft function compared to standard CNI therapy, if they remained on everolimus treatment. Urinary albumin excretion may be a marker of generalized endothelial or vascular damage, and graft function in patients with renal or systemic endothelial damage may deteriorate due to late conversion to everolimus with CNI minimization.

Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney: Special references to HIF-1 dependent gene expression of profibrogenic molecules

The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO. Various factors promoting fibrosis were up-regulated during the development of fibrosis. HIF-1 dependent gene expression of profibrotic molecules, plasminogen activator inhibitor 1, connective tissue growth factor, lysyl oxidase like 2 and transglutaminase 2 was observed in the obstructed kidney but such HIF-1 dependency was limited to the early onset of renal fibrosis. Global HIF-1 deletion tended to attenuate interstitial collagen I deposition at 3 days but had no effects thereafter. It is suggested that HIF-1 dependent profibrogenic mechanisms are operating at the early onset of renal fibrosis but its contribution declines with the progression in mouse UUO model.

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

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.