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Objective Asymptomatic renal immunoglobulin A (IgA) deposition occurs in healthy subjects, but its etiologic role in disease is unclear. Galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgA nephropathy. We investigated Gd-IgA1 deposition in transplanted kidneys that were considered healthy showing subclinical latent IgA deposition one hour after transplantation. Methods A total of 723 transplanted kidney specimens biopsied 1 h after kidney transplantation from 2009 to 2016 at Nagoya Red Cross Hospital were examined. A total of 81 cases of IgA deposition were extracted, and 41 were ultimately studied. Double immunofluorescence staining for Gd-IgA1 and IgA was conducted to investigate the role of Gd-IgA1 in subclinical IgA deposition. Results Light microscopy findings for the 41 cases indicated only minor glomerular abnormalities. Immunofluorescence analyses revealed that all cases were positive for IgA. C3, IgG, and IgM positivity rates were 78.0%, 7.3%, and 60.9%, respectively. All 41 cases were positive for Gd-IgA1, which merged with IgA deposition in immunofluorescence double staining. IgA disappeared in 26 of 40 cases (65.0%) 1 year after kidney transplantation. In contrast, IgA redeposition was observed in three cases. Conclusion Gd-IgA1 was demonstrated in all transplanted kidneys, with latent IgA deposition noted in otherwise healthy kidneys. Deposition of Gd-IgA1 might indicate the initial stage of IgA nephropathy; however, additional factors, such as IgG deposition, are required for the ultimate development of IgA nephropathy.

Background Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. Methods Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder–decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. Results Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. Conclusions Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Context Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have the potential to improve native kidney function. Objective This work aimed to elucidate the possible protective effects of GLP-1 RAs on kidney graft function after successful kidney transplantation (KTX). Methods This retrospective cohort study included all KTX recipients (KTRs) at our facility with type 2 diabetes who were followed up from 1 month post-transplantation for 24 months or longer as of December 31, 2020. We investigated associations between the use of GLP-1 RAs and other antidiabetic medications (non–GLP-1 RAs) and the risk of sustained estimated glomerular filtration rate (eGFR) reduction (40% reduction compared with baseline for 4 months) for KTRs with type 2 diabetes. We calculated the propensity score of initiating GLP-1 RAs compared with that of initiating non–GLP-1 RAs as a function of baseline covariates using logistic regression. The inverse probability of the treatment-weighted odds ratio was estimated to control for baseline confounding variables. Sodium-glucose cotransporter 2 inhibitor use was a competing event. The primary outcome was sustained eGFR reduction of at least 40% from baseline for 4 months post-transplantation. Results Seventy-three patients were GLP-1 RA users and 73 were non–GLP-1 RA users. Six patients and 1 patient in the non–GLP-1 RA and GLP-1 RA groups had sustained eGFR reduction. GLP-1 RA use after KTX was associated with a lower risk of sustained eGFR reduction. Conclusion GLP-1 RAs resulted in lower eGFR reduction compared with non–GLP-1 RAs and may contribute to better kidney graft survival after KTX.

Light chain deposition disease (LCDD) is a rare manifestation of monoclonal gammopathy, which can lead to renal failure. We previously reported a detailed recurrence process in a case of LCDD after renal transplantation. To the best of our knowledge, no report has described the long-term clinical course and renal pathology findings of recurrent LCDD in patients after renal transplantation. In this case report, we describe the long-term clinical presentation and changes in renal pathology of the same patient after early LCDD relapse in a renal allograft. A 54-year-old woman with recurrent immunoglobulin A λ-type LCDD in an allograft was admitted one year post-transplant for bortezomib plus dexamethasone therapy. At 2 years post-transplantation, a graft biopsy performed after complete remission was achieved, showing some glomeruli with residual nodular lesions similar to the pre-treatment renal biopsy findings. However, the enlarged subendothelial space disappeared. She remained in complete remission serologically for 6 years. Subsequently, the ratio of serum κ/λ-free light chains decreased gradually. She underwent a transplant biopsy approximately 12 years after renal transplantation due to increased proteinuria and decreased renal function. Compared with the previous graft biopsy, almost all glomeruli showed advanced nodule formation and subendothelial expansion. Because the LCDD case relapsed after long-term remission following renal transplantation, protocol biopsy monitoring might be necessary.

Introduction Owing to organ shortage, the number of kidney transplantation (KT) involving older adult living donors is increasing. We aimed to investigate the effects of living-donor age and donor-recipient age differences on KT outcomes. Methods This single-center, retrospective cohort study involved 853 adult LDKTs performed between January 2008 and December 2018. Recipients were stratified into the following 5 groups based on donor age and donor-recipient age difference: donor age, 30 to 49 years and age difference, −10 to 15 years; donor age, 50 to 69 years and age difference, −10 to 15 years; donor age, 50 to 69 years and age difference, 15 to 40 years; donor age, 70 to 89 years and age difference, −10 to 15 years; and donor age, 70 to 89 years and age difference, 15 to 40 years (groups 1, 2, 3, 4, and 5, respectively). As a primary outcome, the risk of graft loss was investigated. The secondary outcomes were postoperative estimated glomerular filtration rates (eGFRs) and mortality rates of recipients. Results Group 4, representing KT between older adult donors and older adult recipients, had the highest graft loss risk and mortality. The eGFRs of the recipients from donors aged 70 to 89 years (groups 4 and 5) were significantly lower than those from donors in the other groups. Although the differences in the eGFR between groups 4 and 5 were not significant, the eGFR of group 4 was lower than that of group 5 at 6 months post-KT. Conclusion LDKTs from older adult donors to older adult recipients resulted in the worst graft survival and mortality rates.

Background Patients with nephrosclerosis display heterogenous clinical phenotypes, often leading to a clinical diagnosis discordant with pathological nephrosclerosis diagnosis. However, little is known about clinical factors associated with clinicopathological discordance of biopsy-proven nephrosclerosis. Methods In a cross-sectional study of 891 patients with biopsy-proven nephrosclerosis registered in the Japan Renal Biopsy Registry (J-RBR) between July 2007 and June 2016, we examined clinical characteristics associated with a pre-biopsy clinical diagnosis discordant with pathological nephrosclerosis diagnosis using multivariable logistic regression with adjustment for relevant clinical characteristics. Results Overall, the mean (SD) age was 58.6 (13.7) years; 67.6% of patients were male; and 63.2% were on antihypertensive drugs. The median estimated glomerular filtration rate (eGFR) was 43.8 mL/min/1.73 m2 and the median proteinuria was 0.5 g/day. Of the 891 patients, 497 (55.8%) had a clinical diagnosis discordant with pathological nephrosclerosis diagnosis, with chronic nephritic syndrome being the most common (> 75%) discordant clinical diagnosis. After multivariable adjustment, age (odds ratio 1.34, [95% confidence interval, 1.16–1.55], per 10 years increase), eGFR (1.10 [1.00–1.21], per 10 mL/min/1.73 m2 increase), and proteinuria (1.20 [1.03–2.16], per 1 g/day decrease) were found to be significantly associated with the clinicopathological discordance. Conclusions Patients with older age, higher eGFR, and lower proteinuria had significantly higher likelihood of being clinically diagnosed with other glomerular disease in patients with biopsy-proven nephrosclerosis. Our findings highlight the heterogeneous clinical phenotypes of nephrosclerosis and suggest the need for continuous improvement of clinical diagnostic accuracy as well as for wider kidney biopsy indications for nephrosclerosis.

Background Pathological findings in Alport syndrome frequently show mesangial proliferation and sometimes incidental IgA deposition, in addition to unique glomerular basement membrane (GBM) changes including thin basement membrane and/or lamellation. However, similar GBM abnormalities are also often observed in IgA nephropathy. Both diseases are also known to show hematuria, proteinuria, and sometimes macrohematuria when associated with viral infection. Therefore, it can be difficult to make a differential diagnosis, even based on clinical and pathological findings. Some recent articles demonstrated that galactose-deficient IgA1 (Gd-IgA1)-specific monoclonal antibody (KM55) could potentially enable incidental IgA deposition to be distinguished from IgA nephropathy. Methods We performed comprehensive gene screening and glomerular Gd-IgA1 and type IV collagen α5 chain immunostaining for five cases with both IgA deposition and GBM changes to confirm that Gd-IgA1 can help to distinguish these two diseases. Results Four of the cases were genetically diagnosed with Alport syndrome (Cases 1–4) and one was IgA nephropathy with massive GBM changes, which had a negative gene test result (Case 5). In Cases 1–4, glomerular Gd-IgA1 deposition was not detected, although there was positivity for IgA in the mesangial area. In Case 5, glomerular Gd-IgA1 deposition was observed. Conclusion Gd-IgA1 expression analysis could clearly differentiate these two disorders. This approach can be applied to identify these two diseases showing identical clinical and pathological findings.

It is unknown whether cholecalciferol supplementation improves allograft outcomes in kidney transplant recipients (KTRs). We conducted a single‐center randomized, double‐blind, placebo‐controlled trial of daily 4000 IU cholecalciferol supplementation in KTRs at 1‐month posttransplant. The primary endpoint was the change in eGFR from baseline to 12‐month posttransplant. Secondary endpoints included severity of interstitial fibrosis and tubular atrophy (IFTA) at 12‐month posttransplant and changes in urinary biomarkers. Of 193 randomized patients, 180 participants completed the study. Changes in eGFR were 1.2 mL/min/1.73 m2 (95% CI; −0.7 to 3.1) in the cholecalciferol group and 1.8 mL/min/1.73 m2 (95% CI, −0.02 to 3.7) in the placebo group, with no significant between‐group difference (−0.7 mL/min/1.73 m2 [95% CI; −3.3 to 2.0], p = 0.63). Subgroup analyses showed detrimental effects of cholecalciferol in patients with eGFR, A randomized, double‐blind, placebo‐controlled trial shows that vitamin D supplementation fails to protect renal transplants, as assessed by estimated glomerular filtration rate and allograft histology.

Dense deposit disease (DDD), a subtype of complement component 3 (C3) glomerulopathy (C3G), results from alternative complement pathway hyperactivity leading to membrane attack complex formation. DDD treatment strategies are limited. We report a case of a 13-year-old girl diagnosed with DDD at 9 years of age, with nephritic and nephrotic syndrome and C3 nephritic factor-negative alternative complement pathway activation. Initial treatment with prednisolone, methylprednisolone pulses (MPs), and mizoribines was effective for 3 years, after which she relapsed. Despite MP treatment followed by prednisolone and mycophenolate mofetil (MMF), her kidney function and proteinuria deteriorated with a high soluble (s)C5b-9 level; she also developed dyspnea and pleural effusion (PE). Three days after the first eculizumab (ECZ) infusion, urine volume increased, respiratory condition improved, PE resolved, and proteinuria decreased in 1 month. Serum creatinine level decreased, and kidney function completely normalized within 7 weeks. The sC5b-9 level normalized, and although proteinuria decreased, nephrotic range proteinuria persisted during ECZ treatment with MMF for 53 weeks, even with increased treatment interval. Thus, complement activation pathway-targeted therapy may be useful for rapidly progressing DDD. Our data support the role of complement pathway abnormalities in C3G with DDD.

Summary While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+CD127− regulatory T cells (edu.Tregs) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg; anti-A/B antibodies were not involved in the Treg-mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.

Mutations in the TTC21B gene have been identified in patients with nephronophthisis and were recently found in some patients with focal segmental glomerulosclerosis. We herein report a Japanese boy with end-stage renal disease due to medullary polycystic kidney disease and primary focal segmental glomerulosclerosis. Next-generation sequencing detected a new compound heterozygous missense mutation in the TTC21B gene. His renal pathological findings and gene mutations have not been previously reported in patients with ciliopathy. For children with severe renal dysfunction, mutations in the TTC21B gene cause both ciliopathy characterized by bilateral polycystic kidney disease and primary focal segmental glomerulosclerosis.

Background Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. Methods A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. Results Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. Conclusions Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Background Renin-angiotensin system inhibitors (RASis) are recommended as the first-line therapy to reduce proteinuria in primary nephrotic syndrome. It is unclear whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy. Methods This retrospective cohort study included adults with primary nephrotic syndrome from causes other than minimal change disease who were enrolled in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, with a 5-year follow-up period, and were not on RASis at enrolment. The exposure was a new RASi prescription, and the outcome was the first CR, defined as a urinary protein level

Soon after the outbreak of the COVID-19 pandemic, many governments began extending financial and other forms of support to micro, small, and medium enterprises (MSMEs) and their workers because smaller firms are more vulnerable to negative shocks to their supply chain, labor supply, and final demand for goods and services than larger firms. Since MSMEs are diverse, however, the severity of the pandemic's impact on them varies considerably depending on their characteristics. Using online survey data of MSMEs from eight developing economies in South, Southeast, and Northeast Asia, this paper attempts to deepen our understanding of the impact of the pandemic on MSMEs, especially their employment, sales revenue, and cash flow. It also characterizes those firms that began participating in online commerce and tries to determine how their use of online commerce and their employment are related in this difficult time. This paper also examines the government support that MSMEs have received and the extent to which it has satisfied their support needs.

BACKGROUND: Approximately 30% of children with steroid-resistant nephrotic syndrome (SRNS) have causative monogenic variants. SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns of glomerular damage. Patients with SRNS mainly exhibit focal segmental glomerulosclerosis (FSGS). There is limited information regarding associations between histologic variants of FSGS (diagnosed using on the Columbia classification) and monogenic variant detection rates or clinical characteristics. Here, we report FSGS characteristics in a large population of affected patients. METHODS: This retrospective study included 119 patients with FSGS, diagnosed using the Columbia classification; all had been referred to our hospital for genetic testing from 2016 to 2021. We conducted comprehensive gene screening of all patients using a targeted next-generation sequencing panel that included 62 podocyte-related genes. Data regarding patients’ clinical characteristics and pathologic findings were obtained from referring clinicians. We analyzed the associations of histologic variants with clinical characteristics, kidney survival, and gene variant detection rates. RESULTS: The distribution of histologic variants according to the Columbia classification was 45% (n=53) FSGS not otherwise specified, 21% (n=25) cellular, 15% (n=18) perihilar, 13% (n=16) collapsing, and 6% (n=7) tip. The median age at end stage kidney disease onset was 37 years; there were no differences in onset age among variants. We detected monogenic disease-causing variants involving 12 of the screened podocyte-related genes in 34% (40 of 119) of patients. The most common genes were WT1 (23%), INF2 (20%), TRPC6 (20%), and ACTN4 (10%). The perihilar and tip variants had the strongest and weakest associations with detection of monogenic variants (83% and 0%, respectively; P

Background Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a rare monoclonal gammopathy of renal significance with dense deposits of monoclonal immunoglobulin. Case presentation We report a 78-year-old Japanese male patient with mild proteinuria and lower extremity edema. Monoclonal immunoglobulin could not be identified in his serum or urine. Although his bone marrow biopsy was negative, renal biopsy found features of membranoproliferative glomerulonephritis (MPGN) with deposition of monoclonal IgG2 kappa. Electron microscopy examination revealed non-organized electron-dense deposits in the subepithelial, and subendothelial mesangial regions. Steroid monotherapy was performed after diagnosis of PGNMID but complete remission was not achieved. Conclusion PGNMID with IgG3 kappa deposits is the most common in cases with the histological feature of MPGN. There are few cases of PGNMID with IgG2 kappa deposits exhibiting MPGN. This report describes a very rare case of PGNMID with the histological feature of MPGN.

Vitamin D deficiency, persistent hyperparathyroidism, and bone loss are common after kidney transplantation (KTx). However, limited evidence exists regarding the effects of cholecalciferol supplementation on parathyroid hormone (PTH) and bone loss after KTx. In this prespecified secondary endpoint analysis of a randomized controlled trial, we evaluated changes in PTH, bone metabolic markers, and bone mineral density (BMD). At 1 month post-transplant, we randomized 193 patients to an 11-month intervention with cholecalciferol (4000 IU/d) or placebo. The median baseline 25-hydroxyvitamin D (25[OH]D) level was 10 ng/mL and 44% of participants had osteopenia or osteoporosis. At the end of the study, the median 25(OH)D level was increased to 40 ng/mL in the cholecalciferol group and substantially unchanged in the placebo group. Compared with placebo, cholecalciferol significantly reduced whole PTH concentrations (between-group difference of -15%; 95% confidence interval [CI] -25 to -3), with greater treatment effects in subgroups with lower 25(OH)D, lower serum calcium, or higher estimated glomerular filtration rate (pint

Introduction: Recent reports have described an increased risk of renal disease in living kidney donors compared with the general population. However, these reports do not detail the outcomes of medically complex living donors (MCLDs) with preoperative comorbidities (PCs), such as hypertension, dyslipidemia, glucose intolerance, and obesity. Analysis of living donors with end-stage renal disease (ESRD) has shown that these PCs may contribute significantly to the development of ESRD. We aimed to evaluate the effect of PCs on postoperative renal function and mortality in MCLDs. Methods: Between January 2008 and December 2016, 807 living-donor kidney transplants were performed in our unit. Of these, 802 donors completed postoperative follow-up of >5 months. Donors were stratified into 4 groups based on the number of PCs present: healthy living donors (HLDs) with no PCs (n = 214) or MCLDs with 1 PC (n = 302), 2 PCs (n = 196), or 3 PCs (n = 90) (denoted MCLD [PC 1], MCLD [PC 2], or MCLD [PC 3], respectively). We compared pathology observation data from baseline biopsy, postoperative estimated glomerular filtration rate (eGFR), postoperative urinary protein concentration, and mortality between HLD and MCLD groups. Results: Interstitial fibrosis, tubular atrophy, glomerulosclerosis, and arteriolosclerosis were more frequent in MCLDs (PC 3) than in HLDs. No significant differences were identified between HLDs and MCLDs in terms of postoperative eGFR and short-term mortality. Overt proteinuria and ESRD were not observed. Conclusions: Appropriate postdonation management of MCLDs with PCs may result in similar outcomes as for HLDs. Keywords: baseline biopsy, estimated glomerular filtration rate, kidney transplantation, medically complex living donor, preoperative comorbidities, proteinuria

Atypical anti-glomerular basement membrane (GBM) nephritis is a rare variant of the classical anti-GBM antibody disease. Patients present with an undetectable anti-GBM antibody but show linear glomerular basement membrane staining for immunoglobulin. We present a 69-year-old man who underwent a living-donor kidney transplant. The aetiology of the renal failure was a focal segmental glomerulonephritis-like lesion resistant to immunosuppressive therapy. A renal graft biopsy revealed diffuse endocapillary hypercellularity, and mild mesangiolysis with linear GBM staining for IgG. The patient was diagnosed with atypical anti-GBM nephritis since the patient tested negative for circulating anti-GBM antibodies. Treatment involved intravenous methylprednisolone, plasma exchange, and rituximab administration. Protocol graft biopsy performed 1 year after the renal transplant showed a focal segmental glomerulonephritis-like lesion possibly progressing from endocapillary hypercellularity and mesangiolysis. These findings were similar to his native kidney biopsy findings. Although classical recurrent anti-GBM nephritis is rare when a renal transplant is performed after decreased disease activity, this case was considered as a case of recurrent atypical anti-GBM nephritis after renal transplant.

Introduction: Living kidney donation improves the lives of individuals with kidney failure; however, recent studies have suggested that living kidney donors may be at a relatively higher risk of reduced renal function than healthy non-donors. We therefore aimed to evaluate the clinical and pathological findings in living kidney donors who developed kidney disease. Methods: From January 1991 to May 2019, 1,625 live kidney donations were performed at our hospital. Among the donors, 7 developed kidney disease after donation and underwent open renal biopsy. We studied the clinical and pathological findings of these patients from their clinical records. Results: There were 3 patients with immunoglobulin A (IgA) nephropathy, 2 with membranous nephropathy, 1 with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, and 1 with secondary focal segmental glomerulosclerosis (FSGS). All patients with IgA nephropathy had latent IgA deposition on their baseline biopsy. One patient with membranous nephropathy demonstrated findings of membranous nephropathy on the baseline biopsy, despite being asymptomatic. All patients, except for those with ANCA-associated nephropathy and secondary FSGS, recovered from the nephritis or maintained an adequate renal function after treatment. Discussion/Conclusion: Baseline biopsy is necessary for assessing the renal condition of kidney donors, and these donors require long-term follow-up based on their baseline biopsy findings. If donors develop kidney disease, appropriate diagnosis and treatment are essential.

Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse.This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors.Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively).The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.

BACKGROUND Nationwide data on allograft kidney biopsies have been limited in number, in contrast to the large amount of accumulated data on native kidney biopsies. In this context, we have surveyed transplant biopsy data based on the nationwide database, the Japan Renal Biopsy Registry (J-RBR). MATERIAL AND METHODS A total of 2430 transplant biopsy cases were registered in the web-based J-RBR from January 2007 to January 2018. We categorized the entries regarding both the purpose of the biopsy and pathological diagnosis, and confirmed transplant glomerular diseases based on the clinical and pathological diagnosis. RESULTS Of the 2430 total transplant biopsy cases, 637 cases, including 9 cases of baseline biopsy, 216 cases of protocol biopsy, and 232 cases of episode biopsy, had a pathological diagnosis, including glomerular diseases, rejection, calcineurin inhibitor nephropathy, and interstitial fibrosis and tubular atrophy. Of these, 127 cases presented with glomerular disease, including 8 cases of baseline biopsy, 23 of protocol biopsy, 59 of episode biopsy, and 37 of unknown purpose). A total of 127 biopsies with glomerular disease revealed a high prevalence of immunoglobulin A nephropathy (n=38, 29.9%), followed by mesangial proliferative glomerulonephritis (n=29, 22.8%) and focal segmental glomerulosclerosis (n=8, 6.3%) when focused on protocol and episode biopsies. CONCLUSIONS The nationwide transplant biopsy database demonstrated the pathological characteristics of 637 cases, including 127 cases of post-transplant glomerular disease. The protocol and episode biopsies included high prevalence rates of IgAN, followed by FSGS.

Soon after the outbreak of the COVID-19 pandemic, many governments began extending financial and other forms of support to micro, small, and medium-sized enterprises (MSMEs) and their workers because smaller firms are more vulnerable to negative shocks to their supply chain, labor supply, and final demand for goods and services than larger firms. Since MSMEs are diverse, however, the severity of the pandemic’s impact on them varies considerably depending on their characteristics. Using online survey data of MSMEs from eight developing economies in South, Southeast, and Northeast Asia, we attempt to deepen our understanding of the impact of the pandemic on MSMEs, especially their employment, sales revenue, and cash flow. We characterize those firms that began participating in online commerce and try to determine how their use of online commerce and their employment are related in this difficult time. We also examine the government support that MSMEs have received and the extent to which it has satisfied their support needs.

Recently, in vitro experiments have demonstrated that anti-blood group A/B antibody binding to endothelial cells induce a protective effect against antibody-mediated injury. This study aimed to clarify the potential clinical benefit of ABO incompatibility in donor-specific HLA antibody (DSA)-induced chronic antibody-mediated rejection (ABMR). We enrolled 215 ABO-incompatible renal transplant (ABO-I) and 467 ABO-identical/compatible renal transplant recipients (ABO-Id/C). The prevalence of de novo DSA production and incidence of biopsy-proven chronic ABMR were compared between the two groups. The incidence of DR-associated de novo DSA was significantly lower in ABO-I than in ABO-Id/C (P = 0.028). Diagnostic biopsy for ABMR was conducted in 54 patients (11 ABO-I and 43 ABO-Id/C). Biopsy-proven chronic ABMR was lower in ABO-I than in ABO-Id/C (27.3% [3/11] vs. 44.2% [19/43]) patients. Our findings suggest that ABO incompatibility may cause low production of DR-associated de novo DSA, possibly resulting in a reduced incidence of chronic ABMR.

Background and Aims Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. MN in adults is most often idiopathic, and risk factors of clinical findings for progressive idiopathic MN (iMN) seems to be older age at onset, male sex, and nephrotic-range proteinuria persisting for several months. Immunosuppressive therapy should be applied to the patients with iMN who have risk factors for progression, however little is known about the most effective regimen of immunosuppressive therapy. In addition, long-term prognosis of iMN for each immunosuppressive regimen is unclear. Most of the patients with iMN at our center were treated by prednisolone (PSL) and cyclosporine (CYA) combination therapy, and commencement of therapy was around the time of renal biopsy. The objective of this study is to assess medium to long-term outcome of treated iMN patients with CYA at our center. Method Retrospective data were collected from January 2000 to December 2014 on all consecutive 1080 native renal biopsy at our center. 102 cases were diagnosed as MN. Of 102 MN cases, 43 cases were iMN, which was IgG4 dominant or codominant in immunofluorescence of IgG subclass. Secondary MN is diagnosed by clinical history of possible drug use, the presence of malignancy, positive serologic tests for both infection and connective tissue diseases, hepatitis B or hepatitis C virus positive, and full house immunofluorescence. Results Of 43 iMN cases, there were 4 cases who were treated with only nonimmunosuppressive therapies, 5 cases who were treated with PSL, and 34 cases who were treated with CYA combination. Immunosuppressive therapy commenced within one month before and after renal biopsy. Immunosuppressive regimen was determined by each doctor. CYA was administered once-daily, and the area under the concentration-time curve up to 4 hour after administration of CYA (AUC0-4h) was determined in each patient. No infectious complications were found. The duration of CYA use was 194.7±848.9 days (median 786.5 days), and follow-up period of CYA group was 3026.4±1608.0 days. There were no significant differences between PSL group and CYA group in age (53.4±20.6 years vs. 64.1±10.6 years, p=0.162), sex (1 male 4 female vs. 23 male 11 female ,p=0.162), urinary protein (1.37±0.65 g/gCre vs. 5.44±3.64 g/gCre, p=0.0679), serum creatinine at the time of renal biopsy (0.66±0.19 mg/dl vs. 1.09±0.57 mg/dl, p=0.352), a 30% eGFR decline (0 cases vs. 2 cases), cases achieved complete remission (CR) (5 cases vs. 26 cases, p=0.196), and time from commencement of immunosuppressive therapy to CR (748.2±795.5 days vs. 422.2±379.9 days, p=0.242). There were no significant differences between non-remission cases in CYA group (8 cases) and remission cases in CYA group (26 cases) in age, sex, and urinary protein, but serum creatinine was significantly greater in non-remission cases than remission cases in CYA group (1.75±1.01 mg/dL vs. 0.94±0.29mg/dL, p=0.0251). There were no significant differences between non-recurrent cases in CYA group (16 cases) and recurrent cases (10 cases) in CYA group in age, sex, urinary protein, and serum creatinine at the time of renal biopsy. Conclusion Between PSL group and CYA group, there were no significant differences in age, and sex at the time of biopsy, and there was a trend that urinary protein was greater in CYA group than in PSL group (p=0.0679). Due to the tendency that urinary protein at the biopsy was greater in CYA group, no significant differences were seen in the remission rate and the time from commencement of immunosuppressive therapy to remission between PSL group and CYA group. Despite long duration of CYA use, infectious complications and renal function deterioration were not seen, so CYA can use safely by dose adjustment by AUC0-4h. Further study is needed to provide enough evidence of effectiveness of CYA combination therapy.

Aim: This study aimed to investigate the incidence of atrial fibrillation (AF) and its prognosis in the patients after dialysis initiation.Methods: A total of 1524 patients with chronic kidney dise...

BackgroundPosttransplant anemia may be a major determinant of chronic allograft nephropathy. However, the impact of correcting anemia on graft function remains controversial.MethodsA 3-year follow-up of an open-label, multicenter, randomized controlled trial involving kidney transplantation recipients examined whether sustained maintenance of target hemoglobin (Hb) concentrations at a high level (12.5–13.5 g/dL, n = 64) with either darbepoetin alfa or epoetin beta pegol would slow the graft function decline rate as the primary efficacy endpoint, compared with maintenance of a low Hb concentration (10.5–11.5 g/dL, n = 63).ResultsThe mean blood pressures in the two groups were well controlled throughout the study. In the high Hb group, mean Hb concentrations increased to >12 g/dL at 3 months, reaching the target range at 18 months. At the end of this study (36 months), the mean Hb concentration was 12.8 ± 0.7 g/dL in the high Hb group and 11.5 ± 1.2 g/dL in the low Hb group. The decline rate of the estimated glomerular filtration (eGFR) rate was considerably greater in the low Hb group (ΔeGFR, −5.1 ± 9.5 mL/min/1.73 m2) than in the high Hb group (−1.0 ± 8.4 mL/min/1.73 m2) (P = 0.02). Of note, only a few high Hb patients developed cardiovascular events and returned to hemodialysis, but the low Hb patients did not.ConclusionThis prospective study suggests that correcting anemia to the target Hb level range (12.5–13.5 g/dL) slows renal function deterioration by >3 years in the chronic phase of allograft nephropathy.

The rate of hepatitis B infection among hemodialysis patients is high. However, it is not clear if this rate reflects the infection rate among patients with chronic kidney disease (CKD). Therefore, we evaluated the rate of hepatitis B infection among patients with CKD. This is an important clinical issue when considering the risk of infection to medical staff when performing invasive procedures in this clinical population. A retrospective, observational study was conducted among stable, non-dialysis patients with CKD who attended a CKD educational program at our hospital, between August 2012 and October 2017. We collected patients' background and markers of hepatitis infection (HBsAg, HBcAb and HBsAb, as well as HBV-DNA when available) from medical records. The data from 496 patients (373 men and 123 women, with a mean age of 69.3 ± 13.0 years and mean level of creatinine of 3.15 ± 1.72 mg/dL, AST of 21.6 ± 10.5 IU/L, and ALT of 17.3 ± 12.5 IU/L), were included in the analysis. The rate of positive testing for hepatitis B virus infection was as follows: HBsAg, 1.6%; HBsAb, 16.5%; and HBcAb, 21.4%. Of the patients with a negative HBsAg test, 20.1% tested positive for HBcAb. Of the 66 patients in whom HBV-DNA testing was performed, 10.6% tested positive. The rate of hepatitis B virus infection was specifically higher among patients ≥71-years-old. In patients with CKD, the rate of HBsAg positivity is high. Rate of HBcAb positivity is higher particularly in older individuals.

Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder of APOA-1 gene characterized by the deposition of apolipoprotein A-I in various organs and can be classified into either hereditary or nonhereditary form in the absence of a family history. Renal disease caused by Apolipoprotein A-I amyloidosis commonly manifested as slowly progressive renal function impairment without heavy proteinuria. Apolipoprotein A-I-related amyloidosis of kidney is of pathogenetic interest because the renal failure is due to peritubular and interstitial amyloid deposits without glomerular deposits. Tubulointerstitial lesion of amyloid deposits was diagnosed in half of carriers of APOA1 gene mutation, only 13% of patients progressed to renal failure requiring hemodialysis or kidney transplantation. Recurrence of apolipoprotein A-I-related amyloidosis after kidney transplantation is very rare. We report a case of a 63-year-old Japanese female without a family history of kidney and/or liver disease who showed slowly progressive renal graft dysfunction without overt proteinuria. Graft biopsy revealed characteristic Congo red stain positive amyloid deposits localized in the renal interstitial area. No glomerular, vascular and tubular amyloid deposits were noted. Laser microdissection-liquid chromatography tandem mass spectrometry-based proteomic analysis elucidated the type of amyloidosis as apolipoprotein A-I amyloidosis. Genetic analysis of DNA sequence study revealed two novel APOA1 gene mutations of Leu202Arg and Lys262Asn. This is a first and very rare case report of the recurrence of non-familial hereditary apolipoprotein A-I amyloidosis in Japanese transplant recipient.

Noninvasive methods for the early diagnosis of chronic antibody-mediated rejection (cAMR) are desired for patients with de novo (dn) donor-specific HLA antibody (DSA). This study aimed to elucidate the clinical relevance of immune-related gene expression in peripheral blood of kidney transplant recipients. The expression levels of fourteen key molecules (Foxp3, CTLA-4, CCR7, TGF-β, IGLL-1, IL-10, ITCH, CBLB, Bcl-6, CXCR5, granzyme B, CIITA, Baff, TOAG-1/TCAIM) related to regulatory/cytotoxic function of immune cells were compared in 93 patients, which were divided into Groups A (clinical cAMR with dn DSA, n = 16), B (subclinical cAMR with dn DSA, n = 17), C (negative cAMR with dn DSA, n = 21) and D (stable function without dn DSA, n = 39). CIITA mRNA expression levels in groups B and C were significantly lower than those in group D (p 0.01). Moreover, the CTLA-4 mRNA expression in group A was significantly higher than that in groups B and C (p 0.01). ROC curve analysis suggested that CIITA (AUC = 0.902) and CTLA-4 (AUC = 0.785) may serve as valuable biomarkers of the stage of dn DSA production and clinical cAMR, respectively. In addition to dn DSA screening, monitoring of CIITA and CTLA-4 in peripheral blood could offer useful information on the time course of the development of cAMR.

The lack of high-quality clinical evidences hindered broad consensus on optimal therapies for primary nephrotic syndromes. The aim of the present study was to compare prevalence of immunosuppressive drug use in patients with primary nephrotic syndrome across 6 regions in Japan. Between 2009 and 2010, 380 patients with primary nephrotic syndrome in 56 hospitals were enrolled in a prospective cohort study [Japan Nephrotic Syndrome Cohort Study (JNSCS)], including 141, 151, and 38 adult patients with minimal change disease (MCD), membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), respectively. Their clinical characteristics were compared with those of patients registered in a large nationwide registry of kidney biopsies [Japan Renal Biopsy Registry (J-RBR)]. The regional prevalence of use of each immunosuppressive drug was assessed among adult MCD, MN, and FSGS patients who underwent immunosuppressive therapy in the JNSCS (n = 139, 127, and 34, respectively). Predictors of its use were identified using multivariable-adjusted logistic regression models. The clinical characteristics of JNSCS patients were comparable to those of J-RBR patients, suggesting that the JNSCS included the representatives in the J-RBR. The secondary major immunosuppressive drugs were intravenous methylprednisolone [n = 33 (24.6%), 24 (19.7%), and 9 (28.1%) in MCD, MN, and FSGS, respectively] and cyclosporine [n = 25 (18.7%), 62 (50.8%), and 16 (50.0%), respectively]. The region was identified as a significant predictor of use of intravenous methylprednisolone in MCD and MN patients. Use of intravenous methylprednisolone for MCD and MN differed geographically in Japan. Its efficacy should be further evaluated in a well-designed trial.

Patients with malignancy have a poorer prognosis than others do, which must be taken into consideration when treating them for chronic kidney disease (CKD). However, there are few studies investigating their prognosis. This was an observational study of 515 (394 men and 121 women) stable non-dialysis patients with CKD who attended a CKD educational program. Mean age was 68.8 ± 13.0 years. Median follow-up was 968.5 days. Mean creatinine was 3.4 ± 1.6 mg/dL. Of these, 63 had malignancy and 452 did not; 20.6% of the former and 11.9% of the latter group died by the end of the study period (P = 0.0548). Malignancy was not associated with all-cause mortality (HR: 1.3475, 95% CI: 0.7202-2.5214, P = 0.3507) but with malignancy-associated mortality (HR: 3.9477, 95% CI: 1.6348-9.5331, P = 0.0023). Renal replacement therapy was not associated with mortality. Since malignancy greatly affects the prognosis, it must be taken into consideration when treating these patients.