ABO-Incompatible Kidney Transplantation After Bone Marrow Transplantation: A Case Report.

Many studies have been made on ABO-compatible kidney transplants following hematopoietic stem cell transplantation. However, there have been few reports on ABO-incompatible kidney transplantation following hematopoietic stem cell transplantation (HSCT). We report on the case of a successful ABO-incompatible kidney transplantation with high titers after bone marrow transplantation experienced no infectious episodes. The patient was a 38-year-old man with end-stage kidney disease resulting from interstitial nephritis induced by drug toxicity or graft-vs-host disease (GVHD). He had received allogeneic bone marrow transplantation from a human leukocyte antigen-identical unrelated donor to treat chronic myelogenous leukemia. The patient with high anti-B antibody titers (IgM 1:1024 IgG 1:256) received a desensitization protocol consisting of 2 doses of rituximab and 5 courses of plasmapheresis. The patient had prolonged depletion of circulating B cells 2 years after the transplant and was infected with cytomegalovirus viremia, pneumocystis jiroveci pneumonia, and adenovirus urinary tract infection at 2, 3, and 17 months post-transplant, respectively. Currently, at 6 years after his transplant, the patient has had no rejection and is in good clinical condition with only mild renal insufficiency. Our results suggest that ABO-incompatible kidney transplantation may be an effective renal replacement therapy for patients with end-stage kidney disease after HSCT, but desensitization in combination with immunosuppressants could lead to a state of over-immunosuppression, causing various infections.

Frailty is associated with dialysis duration before transplantation in kidney transplant recipients: A Japanese single-center cross-sectional study.

OBJECTIVES: To investigate the prevalence of frailty, and the relationship of frailty based on the Kihon Checklist criteria with dialysis duration before transplantation and time after transplantation in kidney transplant recipients. METHODS: This study was a single-center, cross-sectional investigation carried out on kidney transplant recipients. To examine the association between the total Kihon Checklist score with time after transplant and dialysis duration before transplant, the multivariable proportional odds logistic regression model was used with adjustment for age, sex, body mass index, estimated glomerular filtration rate and serum albumin levels. RESULTS: Out of 205 kidney transplant recipients enrolled in this study, frail, prefrail and robust recipients accounted for 11.2%, 26.8% and 62.0%, respectively. Dialysis duration before transplantation was associated with frailty, but time after transplant was not associated with frailty. CONCLUSIONS: The prevalence of frailty in kidney transplant recipients is approximately 11%, and it is associated with the duration of pretransplant dialysis. These findings suggest that a shorter dialysis duration might be beneficial for preventing frailty in kidney transplant recipients.

Association of sarcopenia with phase angle and body mass index in kidney transplant recipients.

Malnutrition is an important risk factor for the development of sarcopenia. Recently, phase angle (PhA) obtained from the bioelectrical impedance analysis is increasingly becoming known as a nutritional status marker and may be considered a good indicator to identify elderly patients at risk of sarcopenia. In this study, we investigated the prevalence of sarcopenia and the relationship between sarcopenia and PhA or body mass index (BMI) as nutritional factors, and evaluated the discrimination performance of these nutritional factors for sarcopenia in 210 kidney transplant recipients. The median age was 55 years and 11.1% had sarcopenia. This prevalence of sarcopenia was lower than previous reports in kidney transplant recipients, maybe because of the differences in sarcopenia definitions and population demographics such as age, sex, race, and comorbidities. Both PhA and BMI were negatively correlated with sarcopenia after adjusting for age, sex, dialysis vintage, time after transplant, presence of diabetes mellitus, hemoglobin, estimated glomerular filtration rate, and the other nutritional factor. The discrimination performance for PhA and BMI had enough power to detect sarcopenia. These results suggest that PhA and BMI can be used in clinical practice to predict sarcopenia in kidney transplant patients.

Conversion From Cyclosporine to Once-Daily Tacrolimus on 50:1 mg Basis: A Short-Term Pilot Study.

OBJECTIVES: In addition to graft dysfunction, renal transplant recipients on cyclosporine may be switched to tacrolimus to reduce its drug-related secondary clinical effects and undesirable cosmetic side effects. However, the dose level of once-daily tacrolimus for these patients has yet to be established. The objective of this prospective study was to confirm the safety of converting stable renal transplant recipients on cyclosporine to once-daily tacrolimus at a 50:1 mg ratio. MATERIALS AND METHODS: Our study enrolled 17 patients receiving cyclosporine who were observed for 3 months. Graft biopsies did not reveal any acute rejection, and the conversion ratio to once-daily tacrolimus was 50:1 mg. Dose adjustments were made to achieve a target tacrolimus trough concentration of 3 to 5 ng/mL at 2 weeks, and graft biopsies were taken after the 3-month observation period. RESULTS: Dose adjustment was required in 7 recipients (41.2%) within 3 months of conversion. None of the recipients had acute cellular rejection or C4d deposition, and the mean estimated glomerular filtration rate of 38.7 ± 11.0 mL/min/1.73 m2 at baseline was significantly improved to 42.0 ± 10.0 mL/min/1.73 m2 at month 3. CONCLUSIONS: Although recipients of renal transplant can be forced to discontinue cyclosporine administration due to undesirable adverse effects, our study showed that a once-daily dose of tacrolimus may be safe when administered at a conversion ratio of 50:1.

Comparison of Glucose Tolerance between Kidney Transplant Recipients and Healthy Controls.

Post-transplant hyperglycemia and new-onset diabetes mellitus after transplantation (NODAT) are common and important metabolic complications. Decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind NODAT. However, the progression of glucose intolerance diagnosed late after kidney transplantation remains clearly unknown. Enrolled in this study were 94 kidney transplant recipients and 134 kidney transplant donors, as the healthy controls, who were treated at our institution. The 75 g-oral glucose tolerance test (OGTT) was performed in the recipients, and the healthy controls received an OGTT before donor nephrectomy. We assessed the prevalence of glucose intolerance including impaired fasting glucose and/or impaired glucose tolerance, as well as insulin secretion and insulin resistance using the homeostasis model assessment, and compared the results between the two groups. Multivariate analysis after adjustment for age, gender, body mass index, estimated glomerular filtration rate, and systolic blood pressure showed that the prevalence of glucose intolerance, insulin resistance, insulin secretion, and 2 h plasma glucose levels were significantly higher in the kidney transplant recipients compared to the healthy controls. Elevation of insulin secretion in kidney transplant recipients may be compensatory for increase of insulin resistance. Impaired compensatory pancreas ß cell function may lead to glucose intolerance and NODAT in the future.

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

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.

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

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.

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

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.

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.

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.

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.

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

The Neurospora crassa UVS-3 epistasis group encodes homologues of the ATR/ATRIP checkpoint control system.

The mutagen sensitive uvs-3 and mus-9 mutants of Neurospora show mutagen and hydroxyurea sensitivity, mutator effects and duplication instability typical of recombination repair and DNA damage checkpoint defective mutants. To determine the nature of these genes we used cosmids from a genomic library to clone the uvs-3 gene by complementation for MMS sensitivity. Mutation induction by transposon insertion and RIP defined the coding sequence. RFLP analysis confirmed that this sequence maps in the area of uvs-3 at the left telomere of LG IV. Analysis of the cDNA showed that the UVS-3 protein contains an ORF of 969 amino acids with one intron. It is homologous to UvsD of Aspergillus nidulans, a member of the ATRIP family of checkpoint proteins. It retains the N' terminal coiled-coil motif followed by four basic amino acids typical of these proteins and shows the highest homology in this region. The uvsD cDNA partially complements the defects of the uvs-3 mutation. The uvs-3 mutant shows a higher level of micronuclei in conidia and failure to halt germination and nuclear division in the presence of hydroxyurea than wild type, suggesting checkpoint defects. ATRIP proteins bind tightly to ATR PI-3 kinase (phosphatidylinositol 3-kinase) proteins. Therefore, we searched the Neurospora genome sequence for homologues of the Aspergillus nidulans ATR, UvsB. A uvsB homologous sequence was present in the right arm of chromosome I where the mus-9 gene maps. A cosmid containing this genomic DNA complemented the mus-9 mutation. The putative MUS-9 protein is 2484 amino acids long with eight introns. Homology is especially high in the C-terminal 350 amino acids that correspond to the PI-3 kinase domain. In wild type a low level of constitutive mRNA is present for both genes. It is transiently induced upon UV exposure.