Japanese Study of the Effects of AMG (α1-Microglobulin) Reduction Rates on Survival (JAMREDS): A Protocol of a Multicenter Prospective Observational Cohort Study.

INTRODUCTION: Recent advances in dialysis therapy have made it possible to remove middle molecules. Removal of small-middle molecules, such as ß2-microglobulin, can now be achieved with conventional hemodialysis (HD), and removal of large-middle molecules has become a target, particularly for α1-microglobulin (AMG, 33 kD). The AMG reduction rate has emerged as a target for improvement of various clinical symptoms, but the effects on prognosis have yet to be determined. The "Japanese study of the effects of AMG (α1-microglobulin) reduction rates on survival" (JAMREDS) was started in April 2020, with the goal of determining if the AMG reduction rate associates with the risk of mortality and cardiovascular disease (CVD) events. METHODS: JAMREDS is a prospective observational study in patients on HD to examine the effects of: (1) AMG reduction rate on survival outcome and CVD events; (2) dialysis treatment modalities (HD, intermittent infusion hemodiafiltration(iHDF), pre/post-dilution online HDF) on survival and CVD events (based on AMG reduction rates with treatment mode); and (3) AMG reduction rates on survival and CVD events in patients undergoing each therapy (iHDF, pre/post-dilution online HDF). The number of planned subjects was 4,000 in preplanning. Data are collected using RED-Cap, which is an EDC system. A total of 9,930 patients were enrolled at the beginning of the study at 59 registered facilities. The JAMREDS observation period will continue until the end of 2023, after which the data will be cleaned and confirmed before analysis. CONCLUSION: This study may provide new evidence for the relationship between the amount of removed large-middle molecules (such as AMG) and the mortality and CVD risk. Comparisons with convection volumes will also be of interest.

Impact of stroke history on the presence of cerebral microbleeds in hemodialysis patients.

INTRODUCTION: Cerebral microbleeds (CMBs) are detected on gradient-echo T2*-weighted magnetic resonance imaging (MRI). Clinically, CMBs are often detected after stroke, including in cases of intracerebral hemorrhage and ischemic cerebrovascular disease. Hemodialysis (HD) patients are widely known to have a high incidence of stroke, and HD patients without stroke history have been reported to have a high prevalence of CMBs. In this study, we investigated whether history of stroke affects the prevalence of CMBs in HD patients. METHODS: A cross-sectional study was performed in 241 HD patients who underwent brain T2*-weighted MRI. We compared the prevalence of CMBs between the patients with and without a history of stroke. Moreover, the relationship between history of stroke and presence of CMBs was examined by multivariate logistic regression analysis. RESULTS: Among these patients, 22 (9.1%) had a history of stroke. CMBs were detected in 70 patients (29.0%). The prevalence of CMBs was significantly higher in patients with a history of stroke compared to those without this history (54.5 vs. 26.5%, p = 0.012). In the multivariable analysis adjusted for background characteristics, history of stroke was a significant and independent factor related to CMBs (OR: 3.24, 95%CI: 1.18-8.89, p = 0.02). DISCUSSION/CONCLUSIONS: As has been reported for non-dialysis patients, our results showed a high prevalence of CMBs in HD patients with a history of stroke, and indicated that a history of stroke is significantly and independently associated with CMBs in HD patients.

A case of anti-aquaporin-4 antibody-positive optic neuritis treated by selective immunoadsorption.

Anti-aquaporin-4 (AQP4) antibody-positive optic neuritis is a condition in which a patient testing positive for anti-AQP4 antibody presents with optic neuritis only. The disease is classified as a neuromyelitis optica spectrum disorder (NMOSD) and is a steroid-resistant refractory optic neuritis. Patients are treated by oral administration of steroids, steroid pulse therapy, and apheresis therapy. The patient in our case was a 48-year-old female who was diagnosed with anti-AQP4 antibody-positive optic neuritis by her ophthalmologist, and was referred to our hospital. Selective plasma exchange (SePE) was initially started, but she strongly preferred treatment as an outpatient due to family circumstances. Therefore, selective immunoadsorption (SeIA) was used from the second session to minimize loss of coagulation factors. The RRs were 16.5-33.3% for anti-AQP4 antibody, 7.48-18.57% for fibrinogen, and 0.8-4.57% for factor XIII. After the 7th SeIA session, the patient was followed up with a maintenance dose of 10 mg/day oral prednisolone as an outpatient at our Department of Ophthalmology. This is the first report to investigate the removal rate (RR) of anti-AQ4 antibody using SeIA. In our case, the anti-AQP4 antibody level before the last SeIA session was still not completely negative, but there was clinical improvement in vision. SeIA was highly effective in maintaining coagulation factor levels. Therefore, our results suggest that SeIA is a safe treatment that can be performed in an outpatient setting.

Safety and Efficacy of Tandem Hemodialysis and Selective Plasma Exchange in Pretransplant Desensitization of ABO-Incompatible Kidney Transplantation.

INTRODUCTION: In patients requiring both hemodialysis (HD) and apheresis, the 2 treatments can be performed simultaneously. At our hospital, selective plasma exchange (SePE) is often performed along with HD for removal of isoagglutinins before ABO-incompatible (ABOi) kidney transplantation. The 2 treatments can be completed within the HD schedule, which allows the treatment time to be shortened. This approach is also less stressful for patients because fewer punctures are required. In this study, we investigated the safety and efficacy of tandem HD and SePE. METHODS: A total of 58 SePE sessions in 30 ABOi kidney transplant recipients were investigated. The SePE circuit was connected in parallel with the HD circuit, and tandem HD and SePE therapy was performed using filtration methods. The SePE sessions were divided into 2 groups: those with SePE monotherapy (group S, n = 20) and those with tandem therapy (group T, n = 38). Changes in transmembrane pressure (TMP), arterial pressure (AP), venous pressure (VP), and decrease in isoagglutinin titers over time were compared between the groups with adjustment for background data. RESULTS: The internal pressures (AP and VP) were higher in group T, and there were significant differences in changes of TMP and AP over time between groups T and S. Membrane exchange was required in 1 case in group T due to coagulation. There was a more significant decrease of immunoglobulin G isoagglutinin titers in group T compared to group S. No case had antibody-mediated rejection after transplantation. DISCUSSION/CONCLUSION: In HD/SePE tandem therapy, internal pressures were higher and TMP and AP tended to increase more compared to SePE monotherapy, but we were able to perform the 2 treatments without any functional problems. Tandem therapy was also effective in decreasing isoagglutinin titers, which suggests that this may be a beneficial treatment modality as apheresis before ABOi kidney transplantation.

Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease.

INTRODUCTION: Splenectomy had been previously performed in ABO-incompatible kidney transplantation to reduce the B cell pool. However, studies have shown that patients undergoing splenectomy may have a lifelong susceptibility to infection and mortality. Splenectomy may affect the incidence of cytomegalovirus (CMV) disease even at a very late stage after transplantation in ABO-incompatible recipients. PATIENTS AND METHODS: Seven patients received their graft from an ABO-incompatible living donor at our institution and underwent splenectomy for B cell reduction. Among them, 3 recipients experienced very late-onset CMV disease approximately 10 years after their transplant and were enrolled in this study. RESULTS: Very late-onset CMV disease occurred at 9 years and 9 months, 15 years, and 13 years and 5 months after transplantation, respectively. Two recipients suffered from CMV retinitis, while one experienced colitis. The age of the patients at onset of CMV disease was 69 years, 42 years, and 71 years, respectively. CONCLUSION: This may be the first report on very late-onset CMV disease after splenectomy in ABO-incompatible kidney transplantation. We should be aware that these recipients can experience very late-onset CMV disease even approximately 10 years after their transplant.

Hypercalcemia Is a Risk Factor for the Progression of Aortic Calcification in Kidney Transplant Recipients.

BACKGROUND/AIMS: Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. MATERIALS: This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. RESULTS: The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). CONCLUSION: The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.

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.

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.

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.

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.