Authorship：Lead author,　Corresponding author   Language：English   Publisher：Kidney360  

Background Regional differences in presentation and clinical course of nephrotic syndrome (NS) have not been studied well because few studies directly compared the data from different intercontinental regions.MethodsWe included adult nephrotic patients with FSGS and minimal change disease (MCD) who received immunosuppressive therapy (IST) in a North American (Nephrotic Syndrome Study Network [NEPTUNE], N=89) or Japanese (Nagoya Kidney Disease Registry [N-KDR], N=288) cohort. Baseline characteristics and rates of complete remission (CR) were compared. Factors associated with time to CR were evaluated by Cox regression models.ResultsNEPTUNE participants had more FSGS (53.9 versus 17.0%) and family history of kidney disease (35.2 versus 3.2%). N-KDR participants were older (median 56 versus 43 years) and demonstrated greater levels of urine protein creatinine ratio (7.73 versus 6.65) and hypoalbuminemia (1.6 versus 2.2 mg/dl). N-KDR participants showed higher proportion of CR (overall: 89.2 versus 62.9%; FSGS: 67.3 versus 43.7%; MCD: 93.7 versus 85.4%). A multivariable model showed that FSGS (versus MCD: hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.20 to 0.41), systolic BP (per 10 mm Hg: HR, 0.93; 95% CI, 0.86 to 0.99), and eGFR (per 10 ml/min per 1.73 m2: HR, 1.16; 95% CI, 1.09 to 1.24) were associated with time to CR. There were significant interactions in patient age (P = 0.004) and eGFR (P = 0.001) between the cohorts.ConclusionsThe North American cohort had more FSGS and more frequent family history. Japanese patients showed more severe NS with better response to IST. FSGS, hypertension, and lower eGFR were shared predictors of poor treatment response. Identifying shared and unique features across geographically diverse populations may help uncover biologically relevant subgroups, improve prediction of disease course, and better design future multinational clinical trials.

DOI： 10.34067/KID.0000000000000133

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Language：English   Publisher：Nephrology Dialysis Transplantation  

Background. The associations of focal segmental glomerulosclerosis (FSGS) histological variants with renal outcomes have rarely been investigated comprehensively by clinically relevant subgroups in this modern age. Methods. Data on 304 (173 nephrotic and 131 non-nephrotic) patients with biopsy-confirmed FSGS from 2010 to 2013 were analyzed using the Japanese nationwide renal biopsy registry. The primary outcome was a composite of a 30% decline in estimated glomerular filtration rate or progression to end-stage kidney disease 5 years from the biopsy. We compared outcomes of FSGS variants according to the Columbia classification using survival analyses. Subgroup analyses were performed based on nephrotic syndrome (NS), immunosuppression and proteinuria remission (PR; proteinuria <0.3 g/day) during follow-up. Additionally, associations of NS, immunosuppression and PR with outcomes were examined for each variant. Results. The distribution of variants was 48% (n ¼ 145) FSGS not otherwise specified, 19% (n ¼ 57) tip, 15% (n ¼ 47) perihilar, 13% (n ¼ 40) cellular and 5% (n ¼ 15) collapsing. The outcome event occurred in 87 patients (29%). No significant differences in the outcome were found among the variants. Subgroup analyses yielded similar results. However, there was a trend toward improved outcome in patients with PR irrespective of variants [hazard ratio adjusted for histological variant and potential confounders (adjusted HR) 0.19 (95% confidence interval 0.10–0.34)]. NS was marginally associated with better outcome compared with non-NS [adjusted HR 0.50 (95% confidence interval 0.25–1.01)]. Conclusions. FSGS variants alone might not have significant impacts on the renal outcome after 5 years, while PR could be predictive of improved renal prognosis for any variant. Specific strategies and interventions to achieve PR for each variant should be implemented for better renal outcomes.

DOI： 10.1093/ndt/gfab267

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Language：English   Publisher：Clinical and Experimental Nephrology  

DOI： 10.1007/s10157-021-02098-5

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Language：English   Publisher：Nephrology Dialysis Transplantation  

Background: The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. Methods: U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period. Results: U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy. Conclusions: Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.

DOI： 10.1093/ndt/gfaa097

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Language：English   Publisher：Journal of Diabetes Investigation  

Aims/Introduction: The relationship between renal function and urinary glucose is poorly understood in diabetes patients who are not using sodium–glucose cotransporter 2 inhibitors. This study aimed to investigate the association of urinary glucose excretion with renal function prognosis in such patients. Materials and Methods: This retrospective cohort study included 1,172 patients with type 1 or 2 diabetes mellitus. Patients were recruited and data were collected between 1 January 2007 and 31 December 2011; follow-up data were collected until 30 June 2015. The primary outcome was set as a 30% decline in estimated glomerular filtration rate relative to baseline. The relationship between this outcome and urinary glucose was investigated using Cox proportional hazards model. For analysis, patients were categorized into two groups: urinary glucose <5 g/day or ≥5 g/day. Interaction terms were analyzed. Results: Multivariate analysis showed that the prognosis of renal function was significantly better in patients with high urinary glucose (≥5 g/day; adjusted hazard ratio 0.58, 95% confidence interval 0.35–0.96; P = 0.034). Significant interactions were observed between high urinary glucose and male sex (hazard ratio 0.33, 95% confidence interval 0.14–0.74; P = 0.007), and between high urinary glucose and longer duration of diabetes (≥10 years; hazard ratio 0.25, 95% confidence interval 0.11–0.58; P = 0.001). Conclusions: The present study suggests that high urinary glucose is associated with prognosis in diabetes patients not taking sodium–glucose cotransporter 2 inhibitors. Measurement of 24-h urinary glucose excretion might have clinical utility for predicting renal prognosis.

DOI： 10.1111/jdi.13428

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Authorship：Lead author   Language：English   Publisher：Scientific Reports  

Focal segmental glomerulosclerosis (FSGS) is a serious condition leading to kidney failure. We aimed to investigate the clinical characteristics of FSGS and its differences compared with minimal change disease (MCD) using cross-sectional data from the Japan Renal Biopsy Registry. In Analysis 1, primary FSGS (n = 996) were stratified by age into three groups: pediatric (< 18 years), adult (18–64 years), and elderly (≥ 65 years), and clinical characteristics were compared. Clinical diagnosis of nephrotic syndrome (NS) was given to 73.5% (97/132) of the pediatric, 41.2% (256/622) of the adult, and 65.7% (159/242) of the elderly group. In Analysis 2, primary FSGS (n = 306) and MCD (n = 1303) whose clinical diagnosis was nephrotic syndrome (NS) and laboratory data were consistent with NS, were enrolled. Logistic regression analysis was conducted to elucidate the variables which can distinguish FSGS from MCD. On multivariable analysis, higher systolic blood pressure, higher serum albumin, lower eGFR, and presence of hematuria associated with FSGS. In Japanese nationwide registry, primary FSGS patients aged 18–64 years showed lower rate of NS than those in other ages. Among primary nephrotic cases, FSGS showed distinct clinical features from MCD.

DOI： 10.1038/s41598-020-80931-9

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Authorship：Lead author   Language：English   Publisher：PLoS ONE  

Background The Columbia classification is widely used for diagnosis of focal segmental glomerulosclerosis (FSGS). In practice, we occasionally encounter segmental glomerular lesions unclassified as Columbia classification. We analyzed the clinical implication of unclassified segmental lesions comparing with Columbia-classified FSGS. Methods A retrospective cohort study from 13 local hospitals in Japan. From 172 biopsy cases diagnosed with FSGS or minimal change disease (MCD)/FSGS spectrum with unclassified segmental lesions, adult patients with nephrotic syndrome who received immunosuppressive therapies were included. The cases are classified by pathology, i.e., typical FSGS lesions sufficiently classified into subgroups of Columbia classification: collapsing (COL), tip (TIP), cellular (CEL), perihilar (PH), and not otherwise specified (NOS), and unclassified by the Columbia classification into three subgroups: “endothelial damage,”; “simple attachment,”; and “minor cellular lesion,”. The response to immunosuppressive treatment and 30% decline of eGFR were compared. Results Among 48 eligible cases, all were Japanese, 34 were typical FSGS; 13 TIP, 15 CEL, 6 NOS, and no COL or PH cases. Fourteen were unclassified cases: endothelial damage (n = 6), simple attachment (n = 5), and minor cellular lesion (n = 3). The median age of overall patients was 60 years old and the median of eGFR and urinary protein creatinine ratio was 51.5 mL/min/1.73m2 and 7.35, respectively. They received similar therapeutic regimen. Kaplan-Meier analysis revealed no significant difference in treatment response between typical FSGS and unclassified cases. Evaluating among the subgroups, endothelial damage, simple attachment and minor cellular lesion showed similar treatment response to TIP or CEL. No significant difference was also observed in the 30% decline of eGFR. Conclusions Japanese adult patients with nephrotic syndrome showing unclassified segmental lesions as Columbia classification may be equivalent clinical impact as Columbia classification of FSGS.

DOI： 10.1371/journal.pone.0244677

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Language：English   Publisher：Arthritis Research and Therapy  

Background: The present study aimed to investigate associations between long-term renal function, whether IgG4-related tubulointerstitial nephritis (TIN) was diagnosed by renal biopsy at initial examination, chronic kidney disease (CKD) stage, and histological stage in patients with IgG4-related TIN. Methods: This study used a retrospective cohort design including almost all patients who underwent renal biopsy at Fujita Health University Hospital and Nagoya University or its affiliated hospitals in Aichi between April 2003 and March 2015 (n = 6977 renal biopsies). The primary outcome was longitudinal changes in eGFR. Main exposures were whether IgG4-related TIN was diagnosed by renal biopsy at the initial examination, CKD stage, and its histological stage. Linear mixed models were performed to examine associations. Results: Of the 6977 samples, there were 24 patients (with 201 records due to repeated measures) with IgG4-related TIN (20 men, mean age, 68.7 ± 9.7 years). They were followed up 6.6 ± 2.8 years after the renal biopsy and underwent glucocorticoid treatment. We found significant increase in eGFR from the baseline to 2 and 6 months after treatment initiation, which was maintained until 60 months. Patients initially diagnosed with IgG4-related TIN had higher eGFR from the baseline (at the start of treatment) to 60 months than those who were not. Compared with patients with CKD stage 3, patients with CKD stages 4 and 5 had lower eGFR at the baseline and other time points. Patients with histological stage B had comparatively lower eGFR at each point than stage A patients. Those mean differences of eGFR were stable from the baseline to 60 months. Conclusions: After the treatment initiation, renal function rapidly improved and maintained for a long period, even with advanced CKD stage. We showed importance of early diagnosis of IgG4-related TIN in maintaining eGFR.

DOI： 10.1186/s13075-020-02320-x

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Authorship：Lead author   Language：English   Publisher：Clinical and Experimental Nephrology  

Background: The Japan Renal Biopsy Registry (J-RBR), the first nation-wide registry of renal biopsies in Japan, was established in 2007, and expanded to include non-biopsy cases as the Japan Kidney Disease Registry (J-KDR) in 2009. The J-RBR/J-KDR is one of the biggest registries for kidney diseases. It has revealed the prevalence and distribution of kidney diseases in Japan. This registry system was meant to be revised after 10 years. Methods: In 2017, the Committees of the Japanese Society of Nephrology started a project for the revision of the J-RBR/J-KDR. The revised system was designed in such a way that the diagnoses of the patients could be selected from the Diagnosis Panel, a list covering almost all known kidney diseases, and focusing on their pathogenesis rather than morphological classification. The Diagnosis Panel consists of 22 categories (18 glomerular, 1 tubulointerstitial, 1 congenital/genetical, 1 transplant related, and 1 other) and includes 123 diagnostic names. The items for clinical diagnosis and laboratory data were also renewed, with the addition of the information on immunosuppressive treatment. Results: The revised version of J-RBR/J-KDR came into use in January 2018. The number of cases registered under the revised system was 2748 in the first year. The total number of cases has reached to 43,813 since 2007. Conclusion: The revised version 2018 J-RBR/J-KDR system attempts to cover all kidney diseases by focusing on their pathogenesis. It will be a new platform for the standardized registration of kidney biopsy cases that provides more systemized data of higher quality.

DOI： 10.1007/s10157-020-01932-6

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Language：English   Publisher：BMJ Open  

Objectives We aimed to examine the validity of the quick Sequential Organ Failure Assessment (qSOFA) score for mortality and bacteraemia risk assessment in Japanese haemodialysis patients. Design This is a retrospective multicentre cohort study. Setting The six participating hospitals are tertiary-care institutions that receive patients on an emergency basis and provide primary, secondary and tertiary care. The other participating hospital is a secondary-care institution that receives patients on an emergency basis and provides both primary and secondary care. Participants This study included haemodialysis outpatients admitted for bacteraemia suspicion, who had blood drawn for cultures within 48 hours of their initial admission. Primary and secondary outcome measures The primary outcome measure was overall in-hospital mortality. Secondary outcomes included 28-day in-hospital mortality and the incidence of bacteraemia diagnosed based on blood culture findings. The discrimination, calibration and test performance of the qSOFA score were assessed. Missing data were handled using multiple imputation. Results Among the 507 haemodialysis patients admitted with bacteraemia suspicion between August 2011 and July 2013, the overall in-hospital mortality was 14.6% (74/507), the 28-day in-hospital mortality was 11.1% (56/507) and the incidence of bacteraemia, defined as a positive blood culture, was 13.4% (68/507). For predicting in-hospital mortality among haemodialysis patients, the area under the receiver operating characteristic curve was 0.61 (95% CI 0.56-0.67) for a qSOFA score ≥2. The Hosmer-Lemeshow χ 2 statistics for the qSOFA score as a predictor of overall and 28-day in-hospital mortality were 5.72 (p=0.02) and 7.40 (p<0.01), respectively. Conclusion On external validation, the qSOFA score exhibited low diagnostic accuracy and miscalibration for in-hospital mortality and bacteraemia among haemodialysis patients.

DOI： 10.1136/bmjopen-2018-028856

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DOI： 10.1007/s10157-018-1648-1

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Predictive values of mesangial proliferation (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and crescents (C) among 19 validation studies of the Oxford Classification of IgA nephropathy (IgAN) were discrepant, especially in Asian patients. These validation studies indicate that cutoffs of MESC score in the Oxford Classification may not be generalizable. Thus, we aimed to improve the clinical value of MESC scores by modifying the cutoff points. A total of 104 patients with IgAN were diagnosed from 2001 to 2012 vai renal biopsy and retrospectively evaluated at Nagoya University Hospital. The cutoff point for modified (M´E´S´C´) was determined using the receiver operating characteristic curve in association with renal outcome in the training cohort. Clinical values of the Oxford MESTC vs M´E´S´C´ cutoff points were analyzed using Kaplan-Meier and Cox regression in association with poor renal outcome in the validation and the entire cohort. Of 104 patients, 12.5% reached poor renal outcome over a median of 6.25 [4.16–9.61] years of follow-up. The modified cutoffs were defined as 40%, 10%, 20%, and 5% in the glomeruli for M´E´S´, and C´ respectively. In univariate analysis, E´, S ´, and T were significantly associated with poor renal outcome, whereas Oxford MESC, M´, and C´ in the training and validation cohort were not associated with poor renal outcome. Using multivariate analysis in the presence of estimated glomerular filtration rate (eGFR), only E´ was a significant predictive factor for poor renal outcome. The E´ with modified cutoff point of 10% significantly improved predictive value for poor renal outcome in IgAN. Therefore, the clinical value of modified cutoff points for M´E´S´C´ scores should be validated with various cohort studies in different regions.

DOI： 10.1371/journal.pone.0214414

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Authorship：Lead author   Language：English   Publisher：American Journal of Nephrology  

Background: In pediatric patients with steroid-sensitive nephrotic syndrome, recent trials have revealed that a 2-month, short-term steroid regimen is not inferior to an extended steroid course. However, the optimal duration of initial steroid therapy for adult steroid-sensitive minimal change disease (MCD) remains unclear. Objectives: The aim of present study was to evaluate the effectiveness of a 2-month, short-term steroid regimen in the treatment of adult steroid-sensitive MCD patients. Method: This was a prospective observational study. Adult patients with steroid-sensitive MCD (n = 35) who were initiated on a short-term steroid regimen between January 2015 and June 2016 were included. The details of the regimen are as follows: (1) prednisolone was administered at an initial dose of 0.8-1.0 mg/kg/day and continued for 4-6 weeks and (2) dosage was reduced to 0.5-0.6 mg/kg/alternate day and continued for 4 weeks. Control patients (n = 140), who were treated using conventional steroid administration, were selected from our previous adult MCD cohort. All patients fulfilled the following criteria: biopsy-proven MCD, age ≥20 years, first episode of nephrotic syndrome, and attainment of complete remission within 4 weeks. The following parameters of patients who received short-term treatment regimen and control patients were compared: any relapse and frequent relapse, adverse events caused by steroid treatment and cumulative steroid dose. Results: Throughout the observation period (median: 17.3 months), 24 (68.6%) patients in the short-term group developed at least one relapse. The short-term regimen showed earlier occurrence of any relapse than the conventional regimen (adjusted hazard ratio [aHR] 2.45; 95% CI 1.51-3.97; p < 0.001), but there was no difference in frequent relapse (aHR 1.31; 95% CI 0.43-3.99; p = 0.63). None of the patients showed any symptoms of adrenal insufficiency after discontinuation of corticosteroids. The cumulative steroid dose during the observational period was significantly lower in the short-term group than in the conventional group. Conclusions: The short-term steroid regimen may represent an effective treatment option that ensures lower steroid exposure when treating adult steroid-sensitive MCD patients.

DOI： 10.1159/000495352

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Language：English   Publisher：Clinical and Experimental Nephrology  

Background: Mycophenolate mofetil (MMF) is recommended as a first-line immunosuppressant to treat lupus nephritis (LN). Prognosis and therapeutic response in LN are known to vary depending on race. We investigated the benefits of MMF and therapeutic drug monitoring (TDM) in the treatment of Japanese LN patients. Methods: In this retrospective cohort study, a total of 20 patients with LN who started MMF treatment were included. Clinical data were collected regularly after MMF administration. We evaluated complete remission (CR) rate as the primary outcome. Predictors of CR were identified using univariate and multivariate analyses. In the research of TDM, the correlation with the area under the curve (AUC) was analyzed at MMF dose, single-point value, treatment response, and adverse events. Results: Overall, 70% of cases showed CR; both flare-ups and refractory cases had favorable results. Cases of LN with nephrotic syndrome (NS) or class III/IV + V showed a significantly lower CR rate (p < 0.005). The ratio of maintaining CR after MMF therapy was as high as 85.7%. In multivariate analysis, NS was an independent negative predictor of CR (HR 0.09, 95% confidence interval 0.01–0.81; p = 0.03). The relationship between AUC and MMF dose was low, and AUC correlated with trough level (r = 0.73). AUC tended to be high in the treatment responder (p = 0.09), but did not correlate with adverse events of infection (p = 0.92). Conclusion: MMF is a beneficial treatment option for Japanese LN patients, and further investigation on TDM-based therapy is needed.

DOI： 10.1007/s10157-018-1590-2

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Language：English   Publisher：BMC Nephrology  

Background: Henoch-Schönlein purpura nephritis (HSPN) is a form of small vessel vasculitis associated with purpura and IgA deposition in the glomeruli. The International Study of Kidney Disease in Children (ISKDC) classification predicts renal prognosis in children with HSPN, but not in adults. Additionally, it is not well known whether the Oxford classification 2016 and/or the Japanese Histologic classification (JHC) are associated with renal outcome. Herein, we investigated the relationship between pathological characteristics and renal outcome among adult patients with HSPN. Methods: A multicenter retrospective cohort study was conducted in adult patients with HSPN who underwent renal biopsy between 2004 and 2014. Two nephrologists classified each patient according to the Oxford classification 2016, JHC, and the ISKDC classification. Renal outcome was defined by a 30% decline in the eGFR and/or end-stage kidney disease. Results: We enrolled 74 adult patients with HSPN (mean age, 47.8 ± 17.4 years; mean eGFR, 76.4 ± 25.8 ml/min/1.73 m 2 ; median proteinuria, 1.40 [IQR: 0.70-2.38] g/day). During a mean follow-up period of 68.0 ± 33.0 months, fourteen patients (18.9%) reached the renal outcome, and all 14 had received immunosuppressive therapy. The log-rank test revealed that event-free renal survival was significantly shorter in patients with endocapillary proliferation (E1) according to the Oxford classification than in those with E0 (p = 0.0072). However, the JHC, ISKDC classification and other Oxford lesions could not demonstrate a significant difference in event-free renal survival. In a multivariate Cox model adjusted for clinical and pathological factors, age (HR, 1.57; 95% CI, 1.12-2.21) and E lesion (HR, 6.71; 95% CI, 1.06-42.7) were independent risk factors for renal outcome. Conclusions: Endocapillary proliferation is significantly associated with renal outcome in adult patients with HSPN, including those receiving immunosuppressive therapy. Other Oxford classification lesions, JHC, and ISKDC classification were not associated with renal outcome.

DOI： 10.1186/s12882-018-1009-z

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Language：English   Publisher：Renal Replacement Therapy  

Background: Serum albumin is a marker of nourishment and inflammation. Although hypoalbuminemia in hemodialysis patients is reported as a risk factor for poor prognosis, few studies describe its effects on infectious diseases specifically. This study aimed to examine the relationship between the serum albumin level on admission and infection-related in-hospital death among hemodialysis patients. Methods: This was a multicenter retrospective observational study that was undertaken in Japan. We reviewed the medical records of 507 hemodialysis patients aged > 18 years, whose blood cultures were obtained based on suspicion of infectious disease, and who were managed at seven Japanese tertiary dialysis units from August 2011 to July 2013. The outcome measure was infection-related in-hospital death. Multivariate logistic regression models adjusted for age, sex, the dialysis vintage, diabetes mellitus, bacteremia, and log C-reactive protein levels were used for the statistical analysis. Results: Four hundred patients were analyzed and allocated to three groups based on their serum albumin levels: marked hypoalbuminemia (< 2.5 mg/dL), mild hypoalbuminemia (≤ 2.5-< 3.5 mg/dL), and normal albumin levels (≤ 3.5 mg/dL). The infection-related in-hospital death rates were 22.9% (n = 11), 12.5% (n = 25), and 4.6% (n = 7), respectively. The multivariate logistic regression models determined that a low serum albumin level was an independent risk factor for infection-related in-hospital death (odds ratio 0.35, 95% confidence interval 0.18-0.66). Conclusions: A low serum albumin level strongly predicts infection-related in-hospital death in hemodialysis patients hospitalized on suspicion of infection. Like those with bacteremia or diabetes mellitus, hemodialysis patients with hypoalbuminemia require careful management of their infections.

DOI： 10.1186/s41100-018-0173-8

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Authorship：Lead author   Language：English   Publisher：PLoS ONE  

Background In patients with adult minimal change disease (MCD), proteinuria relapse is a problem to solve. However, the optimal relapse treatment regimen remains unclear regarding steroid dose. We described the treatment pattern of adult MCD patients and evaluated the appropriate steroid dose for relapse treatment. Methods This retrospective multicenter cohort study included 192 patients with adult biopsy-proven MCD from 14 hospitals in Japan. The prescription pattern of immunosuppressive drugs in relapse was reviewed. To assess the association between steroid dose used for relapse and subsequent outcomes, data of patients with tapered prednisolone (PSL) dosage to <10 mg/day before the first relapse in whom the dose was subsequently increased to 10 mg/day were extracted and assigned to the High-PSL or Low-PSL groups, based on the median dose of 20 mg/day. Multivariate Cox proportional hazard model and propensity score analysis with multiple imputations were conducted to compare their clinical course. Results During a median observation period of 37.6 months, 186/192 (96.9%) patients achieved complete remission (CR) and 100 (52.1%) relapsed. The median urinary protein level at the first relapse was 3.12 g/gCr or g/day. The proportion of non-steroidal immunosuppressant use increased with relapses; cyclosporine was the most common. No significant differences were found in the second relapse, frequent relapses, or adverse events between High-PSL (n = 34) and Low-PSL (n = 36) groups. A multivariate Cox proportional hazard model revealed that the hazard ratios adjusted with propensity score for the second relapse were 0.94 (High-PSL vs. Low-PSL; 95% confidence interval, 0.42–2.10; P = 0.88) and 0.82 (PSL dose per 10 mg/day; 95% confidence interval, 0.58–1.16; P = 0.25). Conclusions Among patients in CR with PSL dose <10 mg/day, higher steroid dose (PSL >20 mg/day) was not associated with favorable outcomes after the first relapse as compared to lower dose (10–20 mg/day).

DOI： 10.1371/journal.pone.0199228

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Language：English   Publisher：Clinical and Experimental Nephrology  

Background: The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). Methods: A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. Results: In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. Conclusions: The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

DOI： 10.1007/s10157-017-1393-x

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Language：English   Publisher：Therapeutic Apheresis and Dialysis  

Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been a major cause of death in hemodialysis patients. We examined whether SAB is a risk for mortality among chronic hemodialysis patients in Japan where the standard vascular access is arteriovenous fistula (AVF). This was a multicenter, retrospective study of maintenance hemodialysis patients with bloodstream infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA) and 42 non-SAB cases. Hospital mortality was higher among SAB cases than non-SAB cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly associated with hospital mortality after adjustment for potential confounders, including type of vascular access (OR 3.26). S. aureus was the leading cause of BSI and hospital mortality among this cohort. Therefore, initial empiric treatment should cover for S. aureus.

DOI： 10.1111/1744-9987.12534

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Language：English   Publisher：PLoS ONE  

Background: Proteinuria is a powerful prognostic factor for end-stage renal disease in IgA nephropathy (IgAN) patients. However, it is not known whether proteinuria exacerbations are related to seasonal changes. Methods: We retrospectively enrolled consecutive patients diagnosed with IgAN by kidney biopsy at our hospital between 2002 and 2014. Proteinuria remission was defined as urinary protein <0.3 g/gCr in two consecutive outpatient urinalyses and exacerbation as urinary protein 0.75 g/gCr. Four seasons were defined: spring (March–May), summer (June–August), autumn (September–November), and winter (December–February). We performed a multivariate analysis to identify factors associated with the second remission following a proteinuria exacerbation. Results: We analyzed 116 patients. Proteinuria remission and exacerbation occurred in 77, and 43 patients, respectively. The incidence of proteinuria exacerbation was significantly higher in autumn and winter than in spring and summer (p = 0.040). The cumulative second remission rate was significantly higher in patients with autumn and winter proteinuria exacerbation than in patients with spring and summer exacerbations (p = 0.0091). In multivariate analyses, exacerbation onset in autumn and winter (hazard ratio [HR], 3.51; 95% confidence interval [CI], 1.41–8.74) and intensive therapy (HR, 2.26; 95% CI, 1.05–4.88) were significantly associated with a second proteinuria remission. Conclusion: In IgAN patients in proteinuria remission, proteinuria exacerbation frequently occurred in autumn and winter. Exacerbations occurring in autumn and winter tended to remit early.

DOI： 10.1371/journal.pone.0187607

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DOI： 10.2169/internalmedicine.53.1301

Language：Japanese  

Authorship：Lead author  

Event date： 2019.11

Language：English   Presentation type：Poster presentation  

Venue：Washington DC   Country：United States  

Event date： 2019.11

Language：English   Presentation type：Poster presentation  

Venue：Washington DC   Country：United States  

Event date： 2019.6

Language：English   Presentation type：Oral presentation (general)  

Venue：Nagoya   Country：Japan  

Event date： 2019.6

Language：English   Presentation type：Poster presentation  

Venue：Nagoya, Japan   Country：Japan  

Event date： 2018.10

Language：English   Presentation type：Poster presentation  

Venue：San Diego, CA   Country：United States  

Event date： 2018.9

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

Venue：徳島   Country：Japan  

Event date： 2018.2

Language：English   Presentation type：Poster presentation  

Venue：Tokyo, Japan   Country：Japan  

Event date： 2018.2

Language：English   Presentation type：Poster presentation  

Venue：Tokyo, Japan   Country：Japan  

Event date： 2018.2

Language：English   Presentation type：Poster presentation  

Venue：Tokyo, Japan   Country：Japan  

Event date： 2017.11

Language：English   Presentation type：Poster presentation  

Country：United States  

Event date： 2017.11

Language：English   Presentation type：Oral presentation (general)  

Venue：New Orleans, LA   Country：United States  

Event date： 2017.5

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：仙台   Country：Japan  

Event date： 2016.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜   Country：Japan  

Event date： 2016.6

Language：Japanese   Presentation type：Poster presentation  

Venue：横浜   Country：Japan  

Event date： 2016.2

Language：English   Presentation type：Poster presentation  

Venue：Nagoya, Japan   Country：Japan  

Event date： 2013.6

Language：English   Presentation type：Poster presentation  

Venue：Hong Kong   Country：China  

Event date： 2013.5

Language：English   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2012.6

Language：English   Presentation type：Poster presentation  

Venue：Honolulu, HI   Country：United States