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Introduction: Glomerular filtration rate (GFR) estimation equations have not been extensively validated in the Indian population. Preliminary data showed that the widely used creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI Cr ) 2009 significantly overestimated GFR in Indians. Newer estimated GFR (eGFR) equations based on creatinine and cystatin C, omitting the race, have been recently proposed. We investigated the performance of race-free eGFR equations in the Indian population., Methods: Patients with chronic kidney disease (CKD) and potential kidney donors attending the outpatient clinic at the Postgraduate Institute of Medical Education and Research Chandigarh, India, were screened for enrolment. GFR was measured by urinary clearance of inulin and plasma clearance of iohexol. Performance of eGFR equations (CKD-EPI Cr(2021) , CKD-EPI Cr-Cys(2021), CKD-EPI Cr(2009) , CKD-EPI Cr-Cys(2012) , CKD-EPI Cys , 2020 Csy-B2M-BTP and 2020 Cr-Csy-B2M-BTP , EKFC cr, EKFC cys , and EKFC cr-cys ) were assessed against measured GFR (mGFR) using bias, precision, and accuracy (root mean square error [RMSE], mean absolute error [MAE] and P 30 [% with eGFR within 30% of mGFR])., Results: A total of 412 subjects (55% with CKD), average age 47 ± 11 years with an equal distribution of males and females were enrolled. The mean mGFR in the study population was 54.2 ± 30.2 ml/min per 1.73 m 2 . The average mGFR in the potential kidney donor's subgroup was 79.5 ± 23.2 ml/min per 1.73 m 2 . Bias was highest for creatinine-based eGFR equations (CKD-EPI cr(2021) : -19.2 [-21.3 to -17.0] ml/min per 1.73 m 2 and CKD-EPI cr(2009) : -17.0 [-19.1 to -15.0] ml/min per 1.73 m 2 ). Cystatin C- (either alone or with other markers) based equations were slightly better but still did not reach P 30  ≥ 80%., Conclusions: Race-neutral CKD-EPI Cr(2021) equation did not significantly improve performance as compared to CKD-EPI Cr(2009) equation. These observations emphasize the need for developing new eGFR equations for Indians and to standardize the mGFR for easy access to care providers for individualized patient care., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Objective: High serum IgA and low serum C3 levels resulting from lectin and alternative pathway activation might be related to IgA nephropathy (IgAN) progression and exacerbation. This study examined whether the serum IgA/C3 ratio can serve as an IgAN progression marker., Methods: (1) This nationwide multicenter retrospective study in Japan included 718 patients with biopsy-confirmed IgAN. The patients whose serum creatinine levels at the time of renal biopsy had doubled were defined as having disease progression. (2) Furthermore, to investigate the pathological significance of a reduction in serum IgA/C3 ratio, we reviewed 63 patients whose serum IgA and C3 data at the end of the observation period were obtained., Results: (1) A Kaplan-Meier analysis of the patients with IgAN revealed that the group with a high serum IgA/C3 (≥ 3.3) had a significantly worse renal outcome. In a multivariate analysis of eGFR ≥ 60 mL/min per 1.73m 2 at the time of biopsy, poor renal outcome was significantly predicted by a serum IgA/C3 ratio of ≥ 3.3. (2) A 15% reduction in the change of serum IgA/C3 ratio was associated with a significantly higher percentage of complete remission of proteinuria. Among the four groups divided by treatment, both the serum IgA/C3 ratio and proteinuria were reduced only in the tonsillectomy and steroid pulse group., Conclusion: The serum IgA/C3 level might reflect the disease activity and be a potent surrogate marker of therapeutic efficacy in patients with IgAN., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Lifestyle modifications by educational sessions are an important component of multidisciplinary treatment for chronic kidney disease (CKD). We attempted to identify the best method to teach these modifications in order to ensure their acceptance by patients and investigated its effectiveness in CKD practice., Methods: This study is a post-hoc analysis of the FROM-J study. Subjects were 876 CKD patients in the advanced care group of the FROM-J study who had received lifestyle modification sessions every 3 months for 3.5 years. Two-hundred and ten males (32.6%) and 89 females (38.2%) showed success in sodium restriction. In this study, we examined factors affecting sodium restriction in these subjects., Results: Subjects received three or more consecutive educational sessions about improvement of salt intake. The median salt-intake improvement maintenance period was 407 days. The number of dietary counseling sessions (OR 1.090, 95%CI: 1.012-1.174) in males and the number of dietary counseling sessions (OR 1.159, 95%CI: 1.019-1.318), CKD stage progression (OR 1.658, 95%CI: 1.177-2.335), and collaboration with a nephrologist (OR 2.060, 95%CI: 1.073-3.956) in females were identified as significant factors improving salt intake. The only factor contributing to the maintenance of improved salt intake was the continuation of dietary counseling (p = 0.013)., Conclusion: An increased number of educational sessions was the only successful approach for males to implement and maintain an improved salt intake. Providing the resources for continuous counseling is beneficial for lifestyle modifications and their maintenance in the long-term management of CKD. Continuous counseling for lifestyle modifications is highly cost-effective., Trial Registration: The FROM-J study was registered in UMIN000001159 on 16/05/2008., (© 2024. The Author(s).)

Objective: The Chronic Kidney Disease (CKD) practice facilitation program in the Frontier of Renal Outcome Modifications in Japan study reduced cardiovascular disease (CVD) events in patients with CKD. 10-year long-term survivors with CKD lived with serious complications, including end-stage kidney disease and CVD. This study aimed to measure health-related quality of life in 10-year long-term CKD survivors and examine the predictors and determinants of clinical indices for measured quality of life (QOL) scores., Methods: The EQ-5D-5L, a generic preference-based instrument, was administered to 1,473 CKD survivors enrolled in the Frontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in Japan study. The 10th-year data collection was performed by either primary care physicians or participants who filled out questionnaires from October 2018 to March 31, 2019., Results: The response rate was 38.2% (423/1,473). The mean QOL score was 0.893 (95% confidence interval (CI), 0.880-0.906), and the median QOL score was 1.000 (interquartile range (IQR), 0.826-1.000). The mean QOL score in participants with renal replacement therapy was 0.824 (95% CI, 0.767-0.881), and the median was 0.828 (IQR, 0.755-1.000). The mean QOL score in participants with CVD was 0.877 (95% CI, 0.811-0.943), and the median was 1.000 (IQR, 0.723-1.000). The mean QOL score in participants with 50% decline in estimated glomerular filtration was 0.893 (95% CI, 0.860-0.926), and the median was 0.889 (IQR, 0.825-1.000). The decrease in QOL scores with baseline CKD stages was significant according to the Jonckheere-Terpstra test for trend (P = .002). Baseline age, systolic blood pressure, and history of hyperuricemia were significant predictors of 10th-year QOL scores., Conclusion: We suggest that CKD complications negatively affect the QOL scores in 10-year long-term survivors with CKD. CKD guideline-based practices, prevention of end-stage kidney disease/CVD and management of hypertension, diabetes and hyperuricemia, might contribute to future health-related quality of life in patients with CKD., (Copyright © 2023. Published by Elsevier Inc.)

Aims/introduction: This multicenter cohort study retrospectively assessed the association between polar vasculosis and the progression of diabetic kidney disease (DKD) in type 2 diabetes., Materials and Methods: We enrolled 811 patients with type 2 diabetes, biopsy-proven DKD, and proteinuria (≥0.15 g/g creatinine [g/day]). The association between polar vasculosis and other kidney lesions was explored. The outcome was DKD progression defined as a composite of renal replacement therapy initiation or 50% decline in estimated glomerular filtration rate (eGFR) from baseline., Results: Of the 811 cases, 677 (83.5%) had polar vasculosis. In multivariate logistic regression analysis, subendothelial widening of the glomerular basement membrane, glomerulomegaly, glomerular class in the Renal Pathology Society classification ≥IIb, vascular lesions, age, eGFR, and hemoglobin A1c were positively associated with polar vasculosis, whereas interstitial fibrosis and tubular atrophy (IFTA) was negatively associated with polar vasculosis. During a median follow-up of 5.2 years, progression of DKD occurred in 322 of 677 (7.4 events/100 person-years) and 79 of 134 (11.4 events/100 person-years) cases with and without polar vasculosis, respectively. Kaplan-Meier analysis showed that polar vasculosis was associated with lower cumulative incidences of DKD progression. Multivariate Cox regression analyses showed that polar vasculosis was associated with a lower risk of DKD progression, regardless of eGFR or proteinuria subgroups. These associations between polar vasculosis and better kidney outcome were unchanged considering all-cause mortality before DKD progression as a competing event., Conclusions: This study showed that polar vasculosis of DKD was associated with less advanced IFTA and a better kidney outcome in type 2 diabetes with proteinuria., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Neutrophil extracellular traps (NETs) are critically involved in microscopic polyangiitis (MPA) pathogenesis, and some patients with MPA possess anti-NET antibody (ANETA). Anti-myosin light chain 6 (MYL6) antibody is an ANETA that affects NETs. This study aimed to determine the significance of anti-MYL6 antibody in MPA., Methods: The influence of anti-MYL6 antibody on NET formation and actin rearrangement necessary for NET formation was assessed by fluorescent staining. An enzyme-linked immunosorbent assay was established to detect serum anti-MYL6 antibody, and the prevalence of this antibody in MPA was determined. Furthermore, the disease activity and response to remission-induction therapy of MPA were compared between anti-MYL6 antibody-positive and anti-MYL6 antibody-negative MPA patients., Results: Anti-MYL6 antibody disrupted G-actin polymerization into F-actin, suppressing phorbol 12-myristate 13-acetate-induced NET formation. Serum anti-MYL6 antibody was detected in 7 of 59 patients with MPA. The Birmingham vasculitis activity score (BVAS) of anti-MYL6 antibody-positive MPA patients was significantly lower than anti-MYL6 antibody-negative MPA patients. Among the nine BVAS evaluation items, the cutaneous, cardiovascular, and nervous system scores of anti-MYL6 antibody-positive MPA patients were significantly lower than anti-MYL6 antibody-negative MPA patients, although other items, including the renal and chest scores, were equivalent between the two groups. The proportion of patients with remission 6 months after initiation of remission-induction therapy in anti-MYL6 antibody-positive MPA patients was significantly higher than in anti-MYL6 antibody-negative MPA patients., Conclusions: Collective findings suggested that anti-MYL6 antibody disrupted actin rearrangement necessary for NET formation and could reduce the disease activity of MPA., (© 2022. The Author(s).)

Background: The life prognosis of elderly patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies-associated vasculitis (MPO-AAV) has been improved by reducing the corticosteroid or cyclophosphamide dose to avoid opportunistic infection. However, many elderly MPO-AAV patients experience recurrence and renal death. An effective and safer maintenance treatment method is necessary to improve the renal prognosis of MPO-AAV., Methods: Patients with MPO-AAV who reached complete or incomplete remission after induction therapy were prospectively and randomly divided into mizoribine (MZR; n = 25) and control (n = 28) groups. The primary endpoint was relapse of MPO-AAV. The patients' serum MZR concentration was measured before (C0) and 3 h after taking the MZR. The maximum drug concentration (Cmax) and the serum MZR concentration curves were determined using population pharmacokinetics parameters. We also assessed the relationship between the MZR concentrations and adverse events. The observation period was 12 months., Results: Fifty-eight MPO-AAV patients from 16 hospitals in Japan were enrolled. Ten patients relapsed (MZR group, n = 6; control group, n = 4; a nonsignificant between-group difference). Changes in the serum MZR concentration could be estimated for 22 of the 25 MZR-treated patients: 2 of the 11 patients who reached a Cmax of 3 μg/mL relapsed, whereas 4 of the 11 patients who did not reach this Cmax relapsed. The treatment of one patient with C0 > 1 μg/mL was discontinued due to adverse events. No serious adverse events occurred., Conclusion: There was no significant difference in the recurrence rate of MPO-AAV between treatment with versus without MZR., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: A recent cost-effectiveness analysis (CEA) study evaluated the widespread diffusion of behaviour modification intervention for patients with chronic kidney disease (CKD). Incorporating this behaviour modification intervention, comprising educational sessions on nutrition/lifestyle and support for regular patient visits, to the current CKD guideline-based practice was found to be cost-effective. This study aimed to examine the affordability of this efficient new practice under the hypothesis that the behaviour modification intervention would be initiated by general physicians (GPs)., Methods: A budget impact analysis was conducted by defining the target population as patients aged 40-74 years with stage-3-5 CKD based on the prevalence of definitive CKD in the Japanese general population. Costs expended by social insurers without discount were counted as budgets. We estimated the annual budget impact for 15 years by running our CEA model, assuming that it would be good for the span., Results: We estimated the number of patients with end-stage kidney disease (ESKD) to decrease by 4,496 in the fifteenth year of the new practice using our CEA model. Compared to that in the current practice, the budget impact as total additional expenditure of the new practice was estimated to be negative by the tenth year in the base case., Conclusions: The widespread diffusion of behaviour modification intervention would contain public health care expenditure over the mid-to-long term, resulting from a reduction in progression to ESKD. We suggest that providing sufficient economic incentives to GPs and strengthening recommendations in CKD guidelines would realise effective GP-initiated interventions., (© 2022. Japanese Society of Nephrology.)

Background: Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin (Hb) concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression., Methods: Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR)  ≥60 mL/min/1.73 m2 at renal biopsy were identified: age 56 (45-63) years; 62.6% men; Hb 13.3 (12.0-14.5) g/dL; eGFR 76.2 (66.6-88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio 534 (100-1480) mg/g Crea. Serum Hb concentration was divided into quartiles: ≤12, 12.1-13.3, 13.4-14.5 and ≥14.6 g/dL. The association between serum Hb concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum Hb concentration to the known risk factors of DKD was assessed., Results: Serum Hb levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ = -0.52; P < 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second and third quartile (the fourth quartile was reference) were 2.74 [95% confidence interval (CI) 1.26-5.97], 2.33 (95% CI 1.07-5.75) and 1.46 (95% CI 0.71-3.64), respectively. Addition of the serum Hb concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global Chi-statistics increased from 55.1 to 60.8; P < 0.001)., Conclusions: Serum Hb concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Introduction: Recent studies have suggested a higher incidence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) in the USA than in Japan. Hyperphosphatemia, a possible risk for CVD, may explain this difference; however, international differences in phosphate parameters in CKD have not been well elaborated., Methods: By using the baseline data from the USA and the Japanese nation-wide, multicenter, CKD cohort studies; the Chronic Renal Insufficiency Cohort Study (CRIC, N = 3,870) and the Chronic Kidney Disease-Japan Cohort Study (CKD-JAC, N = 2,632), we harmonized the measures and compared clinical parameters regarding phosphate metabolism or serum phosphate, fibroblast growth factor-23 (FGF23), and parathyroid hormone (PTH), in the cross-sectional model., Results: Multivariable linear regression analyses revealed that serum phosphate levels were significantly higher in CRIC across all levels of estimated glomerular filtration rate (eGFR) with the greatest difference being observed at lower levels of eGFR. Serum FGF23 and 25-hydroxy vitamin D (25OHD) levels were higher in CRIC, while PTH levels were higher in CKD-JAC at all levels of eGFR. Adjustments for demographics, 25OHD, medications, dietary intake or urinary excretion of phosphate, PTH, and FGF23 did not eliminate the difference in serum phosphate levels between the cohorts (0.43, 0.46, 0.54, 0.64, and 0.78 mg/dL higher in CRIC within eGFR strata of >50, 41-50, 31-40, 21-30, and ≤20 mL/min/1.73 m2, respectively). These findings were consistent when only Asian CRIC participants (N = 105) were included in the analysis., Conclusion: Serum phosphate levels in CRIC were significantly higher than those of CKD-JAC across all stages of CKD, which may shed light on the international variations in phosphate parameters and thus in cardiovascular risk among CKD patients. The key mechanisms for the substantial differences in phosphate parameters need to be elucidated., (© 2022 S. Karger AG, Basel.)

This study developed low-cost and highly sensitive immunoassay devices possessing the ability to rapidly analyze urine samples. Further, they can quantitatively detect three biomarkers indicating renal injury: monocyte chemotactic protein 1 (MCP-1), angiotensinogen (AGT), and liver-type fatty acid binding protein (L-FABP). The devices were used to successfully estimate the concentrations of the three biomarkers in urine samples within 2 min; the results were consistent with those obtained via conventional enzyme-linked immunosorbent assay (ELISA), which requires several hours. In addition, the estimated detection limits for the three biomarkers were comparable to those of commercially available ELISA kits. Thus, the proposed and fabricated devices facilitate high-precision and frequent monitoring of renal function.

Objectives: Chronic kidney disease (CKD) is a significant public health problem. An advanced, or innovative, CKD care system of clinical practice collaboration among general physicians (GPs), nephrologists, and other healthcare workers achieved behavior modification in patients with Stage 3 CKD in the Frontier of Renal Outcome Modifications in Japan (FROM-J) study. This behavior modification intervention consisted of educational sessions on nutrition and lifestyle, as well as encouragement of patients' regular visits. The intervention contributed to slowing CKD progression. This study aimed to evaluate the cost-effectiveness of the widespread diffusion of the behavior modification intervention proven effective by the FROM-J study., Methods: A cost-effectiveness analysis was carried out to compare the behavior modification intervention with the current practice recommended by the latest CKD clinical guidelines for GPs. A Markov model with a societal perspective under Japan's health system was constructed. We assumed that the behavior modification intervention proven effective by the FROM-J study would be initiated by GPs for targeted patient cohorts-patients aged 40-74 years with Stage 3 CKD-as a part of the innovative CKD care system., Results: The incremental cost-effectiveness ratio for the behavior modification intervention compared with current guideline-based practice was calculated as 145,593 Japanese yen (¥; $1,324 United States dollars [$]) per quality-adjusted life year (QALY)., Conclusions: Using the suggested value of social willingness to pay for a one-QALY gain in Japan of ¥5 million (US$45,455) as the threshold to judge cost-effectiveness, the behavior modification intervention is cost-effective. Our results suggest that diffusing the behavior modification intervention proven effective by the FROM-J study could be justifiable as an efficient use of finite healthcare resources. GPs could be encouraged to initiate this intervention by revising the National Health Insurance fee schedule and strengthening clinical guidelines regarding behavior modification interventions., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Data on the association between longitudinal trajectory patterns of albuminuria and subsequent end-stage kidney disease (ESKD) and all-cause mortality in diabetic kidney disease (DKD) are sparse., Research Design and Methods: Drawing on nationally representative data of 329 patients with biopsy-proven DKD and an estimated glomerular filtration rate above 30 mL/min/1.73 m 2 at the time of biopsy, we used joint latent class mixed models to identify different 2-year trajectory patterns of urine albumin to creatinine ratio (UACR) and assessed subsequent rates of competing events: ESKD and all-cause death., Results: A total of three trajectory groups of UACR were identified: 'high-increasing' group (n=254; 77.2%), 'high-decreasing' group (n=24; 7.3%), and 'low-stable' group (n=51; 15.5%). The 'low-stable' group had the most favorable risk profile, including the baseline UACR (median (IQR) UACR (mg/g creatinine): 'low-stable', 109 (50-138); 'high-decreasing', 906 (468-1740); 'high-increasing', 1380 (654-2502)), and had the least subsequent risk of ESKD and all-cause death among the groups. Although there were no differences in baseline characteristics between the 'high-decreasing' group and the 'high-increasing' group, the 'high-decreasing' group had better control over blood pressure, blood glucose, and total cholesterol levels during the first 2 years of follow-up, and the incidence rates of subsequent ESKD and all-cause death were lower in the 'high-decreasing' group compared with the 'high-increasing' group (incidence rate of ESKD (per 1000 person-years): 32.7 vs 77.4, p=0.014; incidence rate of all-cause death (per 1000 person-years): 0.0 vs 25.4, p=0.007)., Conclusions: Dynamic changes in albuminuria are associated with subsequent ESKD and all-cause mortality in DKD. Reduction in albuminuria by improving risk profile may decrease the risk of ESKD and all-cause death., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

It is well-known that hypertension exacerbates chronic kidney disease (CKD) progression, however, the optimal target blood pressure (BP) level in patients with CKD remains unclear. This study aimed to assess the optimal BP level for preventing CKD progression. The risk of renal outcome among different BP categories at baseline as well as 1 year after, were evaluated using individual CKD patient data aged between 40 and 74 years from FROM-J [Frontier of Renal Outcome Modifications in Japan] study. The renal outcome was defined as ≥ 40% reduction in estimated glomerular filtration rate to < 60 mL/min/1.73 m 2 , or a diagnosis of end stage renal disease. Regarding baseline BP, the group of systolic BP (SBP) 120-129 mmHg had the lowest risk of the renal outcome, which increased more than 60% in SBP ≥ 130 mmHg group. A significant increase in the renal outcome was found only in the group of diastolic BP ≥ 90 mmHg. The group of BP < 130/80 mmHg had a benefit for lowering the risk regardless of the presence of proteinuria, and it significantly reduced the risk in patients with proteinuria. Achieving SBP level < 130 mmHg after one year resulted in a 42% risk reduction in patients with SBP level ≥ 130 mmHg at baseline. Targeting SBP level < 130 mmHg would be associated with the preferable renal outcome.Clinical Trial Registration-URL: https://www.umin.ac.jp/ctr/ . Unique identifier: UMIN000001159 (16/05/2008)., (© 2021. The Author(s).)

Background: Effective prognostic markers are needed for antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study evaluated the clinical associations of serum vascular endothelial growth factor-A (sVEGF-A) and sVEGF-A 165 b (an antiangiogenic isoform of VEGF-A) concentrations with time to remission of AAV in a nationwide Japanese prospective follow-up cohort., Methods: We collected samples from patients with AAV who were enrolled in the nationwide Japanese cohort study (RemIT-JAV-RPGN). We measured sVEGF-A and sVEGF-A 165 b concentrations using enzyme-linked immunosorbent assays in 57 serum samples collected 6 months before and after initiation of AAV treatment. Patients were classified based on AAV disease subtypes: microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA)., Results: Results revealed significant reductions in sVEGF-A and sVEGF-A 165 b concentrations in patients with microscopic polyangiitis and EGPA, respectively. However, despite the comparable concentrations of sVEGF-A and sVEGF-A 165 b during the 6 months of treatment in granulomatosis with polyangiitis patients, correlation analysis revealed that the differences in log 2 -transformed concentrations of sVEGF-A and sVEGF-A 165 b were inversely correlated with time to remission in granulomatosis with polyangiitis patients., Conclusion: These results suggest that sVEGF-A and -A 165 b can serve as potential markers of time to remission in patients with granulomatosis with polyangiitis.

Background: Steroid pulse therapy with tonsillectomy is known as a major treatment for IgA nephropathy (IgAN). However, its protocol was different among institutions and the effects of varying the number of steroid pulses remain unclear., Methods: From a total of 1,174 IgAN patients in a multicenter retrospective cohort analysis in Japan, 195 patients were treated by tonsillectomy combined with corticosteroid. They were divided into four groups based on the number of administered steroid pulses from 0 to three (TSP0-3), and remission of urinary abnormalities and renal survival until 1.5-fold increase in serum creatinine level from baseline were analyzed among the four groups and between TSP1 and TSP3., Results: Among the four groups, renal function was relatively good when the estimated glomerular filtration rate was approximately 80-90 mL/min/1.73m 2 and proteinuria was relatively mild (< 1.0 g/gCre). The ratio of patients who developed renal dysfunction was < 5% in all groups, and the cumulative renal survival rate by Kaplan-Meier analysis was similar among groups (log-rank test, p = 0.37), despite varying clinical backgrounds and treatments. After adjustment of the background variables between TSP1 and TSP3, the remission rates of urinary abnormalities were similar and the renal survival rate also remained similar (66.8 vs. 85.4%, p = 0.45)., Conclusions: In patients with mild proteinuria and good renal function, the number of steroid pulses did not affect the renal outcome in steroid pulse therapy with tonsillectomy. The adaptation and protocols, such as the number of steroid pulses, should be determined for each IgAN patient's background.

Background: The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan., Patients and Methods: Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified., Results: Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593-4.745, p = 0.000) in the multivariate Cox's model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0., Conclusion: Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.

Background: Rapidly progressive glomerulonephritis (RPGN) has been known to have a poor prognosis. Although evidence across adult RPGN cases has accumulated over many years, the number of case series in adolescents and young adults has been limited, requiring further studies., Methods: A total of 1,766 cases from 1989 to 2007 were included in this nationwide questionnaire survey, led by Intractable (former name, Progressive) Renal Diseases Research, Research on intractable disease, from the Ministry of Health, Labour and Welfare of Japan. To elucidate age-related differences in 2-year patient and renal survival rates, the cases were divided into the following four groups: children (0-18 years), young adults (19-39 years), the middle-aged (40-64 years), and the elderly (over 65 years)., Results: Of the 1,766 total RPGN cases, antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis comprised 1,128 cases (63.9% of all RPGN cases), showing a tendency to increase with age. Two-year patient survival for RPGN was 93.9% among children, 92.6% in young adults, 83.2% in the middle-aged, and 68.8% in the elderly. The younger group (children plus young adults) showed a clearly higher survival rate compared to the older group (middle-aged plus elderly) (p<0.05). ANCA-associated glomerulonephritis also showed similar age-related results with all RPGN cases. The comparison of renal prognosis showed no statistically significant differences both in RPGN and in ANCA-associated GN., Conclusion: The present study described the age-dependent characteristics of the classification of RPGN, especially focusing on a better prognosis of the younger group in patient survival both in RPGN and in ANCA-associated GN., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The speed of declining kidney function differs among patients with diabetic nephropathy. This study was undertaken to clarify clinical and pathological features that affect the speed of declining kidney function in patients with diabetic nephropathy., Research Design and Methods: This study was design as multicenter retrospective study. The subjects (377 patients with diabetic nephropathy diagnosed by kidney biopsy at 13 centers in Japan) were classified into three groups based on the estimated glomerular filtration rate (eGFR) declining speed. The eGFR increasing group, the control group, and the eGFR declining group were divided at 0 and 5 mL/min/1.73 m 2 /year, respectively. Characteristics of clinicopathological findings of declining kidney function were evaluated., Results: The mean observation period of this study was 6.9 years. The control group, the eGFR increasing group, and the eGFR declining group included 81, 66, and 230 patients, respectively. The incidences of composite kidney events represented by 100 persons/year were 25.8 in the eGFR declining group and 2.0 in the eGFR increasing group. After adjustment for age, sex, systolic blood pressure, hemoglobin, and urinary albumin levels, three clinicopathological findings (urinary albumin levels, presence of nodular lesion, and mesangiolysis) were risk factors for inclusion in the eGFR declining group (the ORs were 1.49, 2.18, and 2.08, respectively). In contrast, the presence of subendothelial space widening and polar vasculosis were characteristic findings for inclusion in the eGFR increasing group (the ORs were 0.53 and 0.41, respectively)., Conclusions: As well as urinary albumin elevation, nodular lesion and mesangiolysis were characteristic pathological features of patients with fast declining kidney function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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: Chronic kidney disease is a known risk factor for end-stage renal and cardiovascular diseases. However, data are limited on the causes of hospitalization in patients with chronic kidney disease of maintenance period. This study aimed to aggregate hospitalization data of CKD patients and to determine the high-risk population. In addition, we compared CKD population to general population., Methods: We conducted a post hoc analysis of the chronic kidney disease-Japan cohort study, a multicenter prospective cohort study of 2966 patients with chronic kidney disease with a median 3.9 years of follow-up. We examined the hospitalization reasons and analyzed the risk factors., Results: We found 2897 all-cause hospitalization events (252.3 events/1000 person-years), a hospitalization incidence 17.1-fold higher than that in an age- and sex-matched cohort from the general Japanese population. Kidney, eye and adnexa, and heart-related hospital admissions were the most common. All-cause hospitalization increased with chronic kidney disease stage and with the presence of diabetes. Patients with diabetes at enrollment had 345.7 hospitalization events/1000 person-years, which is considerably higher than 196.8 events/1000 person-years for those without diabetes. Survival analysis, using hospitalization as an event, showed earlier all-cause hospitalization with the progression of chronic kidney disease stage and diabetes. Cardiovascular disease hospitalizations were more strongly influenced by diabetes than chronic kidney disease stage., Conclusions: Patients with chronic kidney disease and diabetes are highly vulnerable to hospitalization for a variety of diseases. These descriptive data can be valuable in predicting the prognosis of patients with chronic kidney disease.

Importance: Immunoglobulin A nephropathy is a major cause of end-stage renal disease worldwide; previous methods of medical management, including use of renin-angiotensin system inhibitors and corticosteroids, remain unproven in clinical trials., Objective: To investigate the possible association between tonsillectomy and outcomes in patients with IgA nephropathy., Design, Setting, and Participants: This cohort study included 1065 patients with IgA nephropathy enrolled between 2002 and 2004 and divided into 2 groups, those who underwent tonsillectomy and those who did not. Initial treatments (renin-angiotensin system inhibitors or corticosteroids) within 1 year after renal biopsy were also evaluated. A 1:1 propensity score matching was performed to account for between-group differences and 153 matched pairs were obtained. Follow-up concluded January 31, 2014. Analysis was conducted between September 11, 2017, and July 31, 2018., Exposure: Tonsillectomy., Main Outcomes and Measures: The primary outcome was the first occurrence of a 1.5-fold increase in serum creatinine level from baseline or dialysis initiation. Secondary outcomes included additional therapy with renin-angiotensin system inhibitors or corticosteroids initiated 1 year after renal biopsy and adverse events., Results: In 1065 patients (49.8% women; median [interquartile range] age, 35 [25-52] years), the mean (SD) estimated glomerular filtration rate was 76.6 (28.9) mL/min/1.73 m2 and the median (interquartile range) proteinuria was 0.68 (0.29-1.30) g per day. In all, 252 patients (23.7%) underwent tonsillectomy within 1 year after renal biopsy and 813 patients (76.3%) did not undergo tonsillectomy. The primary outcome was reached by 129 patients (12.1%) during a median (interquartile range) follow-up of 5.8 (1.9-8.5) years. In matching analysis, tonsillectomy was associated with primary outcome reduction (hazard ratio, 0.34; 95% CI, 0.13-0.77; P = .009). In subgroup analyses, benefit associated with tonsillectomy was not modified by baseline characteristic differences. Those undergoing tonsillectomy required fewer additional therapies 1 year following renal biopsy (adjusted hazard ratio, 0.37; 95% CI, 0.20-0.63; P < .001) without increased risks for adverse events, except transient tonsillectomy-related complications., Conclusions and Relevance: This study found that tonsillectomy was associated with a lower risk of renal outcomes in patients with IgA nephropathy. The potential role of tonsillectomy should be considered for preventing end-stage renal disease in patients with IgA nephropathy.

Objective: Clinicopathological characteristics, renal prognosis, and mortality in patients with type 2 diabetes and reduced renal function without overt proteinuria are scarce., Research Design and Methods: We retrospectively assessed 526 patients with type 2 diabetes and reduced renal function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m 2 ), who underwent clinical renal biopsy and had follow-up data, from Japan's nationwide multicenter renal biopsy registry. For comparative analyses, we derived one-to-two cohorts of those without proteinuria versus those with proteinuria using propensity score-matching methods addressing the imbalances of age, sex, diabetes duration, and baseline eGFR. The primary end point was progression of chronic kidney disease (CKD) defined as new-onset end-stage renal disease, decrease of eGFR by ≥50%, or doubling of serum creatinine. The secondary end point was all-cause mortality., Results: Eighty-two patients with nonproteinuria (urine albumin-to-creatinine ratio [UACR] <300 mg/g) had lower systolic blood pressure and less severe pathological lesions compared with 164 propensity score-matched patients with proteinuria (UACR ≥300 mg/g). After a median follow-up of 1.9 years (interquartile range 0.9-5.0 years) from the date of renal biopsy, the 5-year CKD progression-free survival was 86.6% (95% CI 72.5-93.8) for the nonproteinuric group and 30.3% (95% CI 22.4-38.6) for the proteinuric group (log-rank test P < 0.001). The lower renal risk was consistent across all subgroup analyses. The all-cause mortality was also lower in the nonproteinuric group (log-rank test P = 0.005)., Conclusions: Patients with nonproteinuric diabetic kidney disease had better-controlled blood pressure and fewer typical morphological changes and were at lower risk of CKD progression and all-cause mortality., (© 2019 by the American Diabetes Association.)

Background: An overweight person is at high risk for hypertensive renal damage. The effect of weight on the association between systolic blood pressure (SBP) and albuminuria remains unknown in patients with histologically diagnosed hypertensive nephrosclerosis., Methods: A total of 97 patients with biopsy-confirmed hypertensive nephrosclerosis were recruited from 13 centers throughout Japan. We examined the relationship between SBP and proteinuria among those who were overweight, which is defined as a body mass index ≥25 kg/m2, and those who were not. We examined the interaction of weight and SBP with albuminuria at baseline and with the changes in estimated glomerular filtration rate (eGFR) during the observational period., Results: Our results included mean age (54 years old), blood pressure (138/80), eGFR (53 ml/min/1.73 m2), and urine albumin levels (0.2 g/day). SBP was significantly correlated with log-transformed urine albumin levels (r = 0.4, P = 0.01) in patients who were overweight (n = 38) compared with patients who were not overweight (n = 59). Multiple regression analysis revealed that the interaction between being overweight and SBP with respect to albuminuria was significantly correlated with the log-transformed urine albumin level (β = 0.39, P = 0.047) and was independent of age, sex, and potential confounding factors. The interaction between weight and SBP ≥140 mm Hg was significantly associated with a greater decrease in eGFR in the following 3 years., Conclusions: Being overweight may enhance susceptibility to hypertensive glomerular damage and may eventually lead to renal progression in patients with hypertensive nephrosclerosis., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The prognostic value of the EUVAS-proposed histopathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis has been evaluated throughout the world. Here, we performed a Japanese nationwide biopsy survey to assess the association between this histopathological classification and renal prognosis after 2-year follow-up in ANCA-associated glomerulonephritis., Methods: We collected 67 renal biopsy materials of the 321 entries in the RemIT-JAV-RPGN cohort study, and assessed their histologies. Based on the EUVAS-proposed histopathological classification and some histological parameters, we statistically evaluated renal survival and the comparison of renal function for 2 years., Results: Based on the histopathological classification, the largest number of biopsy samples belonged to the Focal class, followed by the Mixed, Crescentic, and Sclerotic classes (n = 30, 19, 10, 8, respectively). Although the number of events might be too low (four patients with renal death) to make this conclusion, the Focal and Mixed classes had higher renal-survival rates compared to the others in the renal-survival curve. Comparing renal function among all classes, the estimated glomerular filtration rate (eGFR) throughout 2-year follow-up period was significantly higher in the Focal class compared to the other 3 classes. The eGFR-values in the Crescentic, Mixed, and Sclerotic classes increased with time. Based on both combined results, the Focal class could be the best prognosis., Conclusion: This histopathological classification was valuable for both the stratification of renal function and the estimation of partial renal survival during 2-year follow-up in ANCA-associated glomerulonephritis.

Histological classification is essential in the clinical management of immunoglobulin A nephropathy (IgAN). However, there are limitations in predicting the prognosis of IgAN based on histological information alone, which suggests the need for better prognostic models. Therefore, we defined a prognostic model by combining the grade of clinical severity with the histological grading system by the following processes. We included 270 patients and explored the clinical variables associated with progression to end-stage renal disease (ESRD). Then, we created a predictive clinical grading system and defined the risk grades for dialysis induction by a combination of the clinical grade (CG) and the histological grade (HG). A logistic regression analysis revealed that the 24-h urinary protein excretion (UPE) and the estimated glomerular filtration rate (eGFR) were significant independent variables. We selected UPE of 0.5 g/day and eGFR of 60 ml/min/1.73 m 2 as the threshold values for the classification of CG. The risk of progression to ESRD of patients with CG II and III was significantly higher than that of patients with CG I. The patients were then re-classified into nine compartments based on the combination of CG and HG. Furthermore, the nine compartments were grouped into four risk groups. The risk of ESRD in the moderate, high, and super-high-risk groups was significantly higher than that in the low-risk group. Herein, we are giving a detailed description of our grading system for IgA nephropathy that predicted the risk of dialysis based on the combination of CG and HG.

In the original publication, there were several errors identified after online publication.

Background: Although left ventricular hypertrophy (LVH) has been established as a predictor of cardiovascular events in chronic kidney disease (CKD), the relationship between the prevalence of LVH and CKD stage during the pre-dialysis period has not been fully examined., Methods: We measured left ventricular mass index (LVMI) in a cross-sectional cohort of participants in the Chronic Kidney Disease Japan Cohort (CKD-JAC) study to identify factors that are associated with increased LVMI in patients with stage 3-5 CKD., Results: We analyzed the baseline characteristics in 1088 participants (male 63.8%, female 36.2%). Diabetes mellitus was the underlying disease in 41.7% of the patients, and mean age was 61.8 ± 11.1 years. LVH was detected in 23.4% of the patients at baseline. By multivariate logistic analysis, independent risk factors for LVH were past history of cardiovascular disease [odds ratio (OR) 2.364; 95% confidence interval ([CI) 1.463-3.822; P = 0.0004], body mass index (OR 1.108; 95% CI 1.046-1.173; P = 0.0005), systolic blood pressure (OR 1.173; 95% CI 1.005-1.369; P = 0.0433), urinary albumin (OR 1.425; 95% CI 1.028-1.974; P = 0.0333), and serum total cholesterol level (OR 0.994; 95% CI 0.989-0.999; P = 0.0174)., Conclusion: The cross-sectional baseline data from the CKD-JAC study shed light on the association between LVH and risk factors in patients with decreased renal function. Further longitudinal analyses of the CKD-JAC cohort are needed to evaluate the prognostic value of LVH in CKD patients.

Background: 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., Methods: 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., Results: 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., Conclusion: Use of intravenous methylprednisolone for MCD and MN differed geographically in Japan. Its efficacy should be further evaluated in a well-designed trial.

Background: The purpose of this study is to determine the association of dipstick-determined trace proteinuria with metabolic syndrome (MetS) and its components in each age, gender, and eGFR category among a large general population., Methods: A total of 270,190 people (102,223 men and 167,967 women) aged 40-74 years were included. Subjects were categorized as having negative, trace, and positive proteinuria by the dipstick method., Results: The prevalence of MetS increased with increasing levels of proteinuria in any estimated glomerular filtration rate (eGFR) category (odds ratios for MetS relative to negative proteinuria: 1.22, 1.23, and 1.25 for trace proteinuria, and 2.19, 1.81, and 1.80 for positive proteinuria among subjects with eGFR of ≥ 90, 60-89, and 45-59 ml/min/1.73 m 2 , respectively). These associations were statistically significant in each age and sex category. Among MetS components, the prevalence of hypertension and diabetes increased with increasing levels of proteinuria (odds ratios for hypertension: 1.23 and 1.87, and odds ratios for diabetes: 1.28 and 2.18 for trace and positive proteinuria, respectively), which were similarly observed in any eGFR category. There were little or no differences in the prevalence of abdominal obesity and dyslipidemia (reduced HDL-cholesterol and/or elevated triglycerides) between the levels of proteinuria., Conclusion: Subjects with dipstick-determined trace proteinuria showed intermediate risk of having MetS, hypertension, and diabetes between negative and positive proteinuria in any eGFR category in a large general population. Thus, MetS components should be checked for subjects with trace proteinuria even in those with normal eGFR for the early prevention of cardiovascular diseases.

Objective: To evaluate clinical links between levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and relapse in patients with ANCA-associated vasculitis (AAV) using a data set from 2 nationwide prospective cohort studies., Methods: From the cohort studies, MPO-ANCA-positive patients who achieved remission during the 6 months after remission induction therapy were enrolled. We measured MPO-ANCA levels at months 0, 3, 6, 12, 18, 24, and at the time of relapse. The primary outcome measure was relapse. A nested case-control analysis and multivariable analysis were performed to investigate the relationship between ANCA reappearance and relapse., Results: Of 271 patients, 183 were classified as having microscopic polyangiitis, 34 as having granulomatosis with polyangiitis, 15 as having eosinophilic granulomatosis with polyangiitis, and 39 were unclassifiable. The median age was 73 years, and 165 (61%) were female. In 195 patients (72%), MPO-ANCA levels decreased to normal levels within 6 months after commencement of treatment, and MPO-ANCA reappeared in 73 of 181 patients (40%) with complete follow-up data. Reappearance of MPO-ANCA was more frequent in patients with relapse than in 75 age- and sex-matched control patients without relapse (odds ratio 26.2 [95% confidence interval 8.2-101], P < 0.0001) after adjustment for confounding factors., Conclusion: Reappearance of MPO-ANCA could be a clinically useful biomarker for predicting relapse in patients with MPO-ANCA-positive AAV in remission. This suggests that routine MPO-ANCA monitoring should be implemented in this patient population., (© 2018, American College of Rheumatology.)

Background: The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis., Methods: The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy., Results: The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m 2 /year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%., Conclusions: This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

Background: Nephrosclerosis is an increasingly reason for dialysis in Japan. However, kidney biopsy specimens for hypertensive nephrosclerosis are very limited; thus, the pathologic evaluation of hypertensive nephrosclerosis currently remains unclear., Methods: Clinical and pathologic data of a total of 184 biopsy-confirmed hypertensive nephrosclerosis patients were collected from 13 centers throughout Japan. Seven pathological findings were assessed in this study. The outcomes of interest for this study were dialysis, composite kidney events, cardiovascular events, and all-cause mortality., Results: The Green and Yellow (G&Y), Orange, and Red groups of the chronic kidney diseases (CKD) heat map contained 36, 57, and 91 cases, respectively. The mean observation period was 7.3 ± 5.2 (median, IQR; 6.1, 2.6-9.7) years. Global glomerulosclerosis (GScle), interstitial fibrosis and tubular atrophy (IFTA), arteriolar hyalinosis in Red exhibited higher scores than those in G&Y and Orange. The incidence rates of the composite kidney end points in 100 person-years for the G&Y, Orange, and Red groups were 1.42, 2.16, and 3.98, respectively. In the univariate Cox analysis for the composite kidney end points, GScle, IFTA and interstitial cell infiltration exhibited statistically significant high hazard ratios (1.18, 1.84, 1.69, respectively). However, after adjustment for clinical and medication data, the Red group in the CKD heat map category was risk factor for the composite kidney end points (HR 9.51)., Conclusions: In summary, although pathologic findings had minor impacts on the prediction of composite outcomes in this study, the clinical stage of the CKD heat map is a good predictor of composite kidney events.

Background: Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians., Methods: GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations., Results: A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m 2 . All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPI Cys was not significantly different from mGFR (p = 0.38). The CKD-EPI Cys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m 2 (95% CI: -0.608 to -0.98)] and highest accuracy (P 30 : 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m 2 ., Conclusion: Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

ETS proto-oncogene 1, transcription factor (ETS1) is involved in various immune responses. Genome-wide association studies on systemic lupus erythematosus in Chinese populations identified the association of ETS1 polymorphism in 3' untranslated region, rs1128334A, which was associated with lower ETS1 expression. In view of substantial sharing of susceptibility genes across multiple autoimmune diseases, we examined whether ETS1 is associated with a rare autoimmune rheumatic disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Association of rs1128334 was tested in 466 Japanese patients with AAV and 1099 healthy controls by logistic regression analysis under the additive model. AAV patients were classified into 285 microscopic polyangiitis (MPA), 92 granulomatosis with polyangiitis (GPA), 56 eosinophilic GPA, and 33 unclassifiable AAV, according to the European Medicines Agency (EMEA) algorithm. Among the patients, 376 were positive for MPO-ANCA and 62 for PR3-ANCA. When the patients were classified according to the EMEA classification, rs1128334A allele was significantly increased in GPA (P = 0.0060, P c  = 0.030, odds ratio (OR), 1.54; 95% confidence interval (CI), 1.13-2.10). With respect to the ANCA specificity, significant association was observed in PR3-ANCA positive AAV (P = 0.0042, P c  = 0.021, OR, 1.72; 95% CI, 1.19-2.49). In conclusion, ETS1 polymorphism was suggested to be associated with GPA and PR3-ANCA positive AAV in a Japanese population.

Background: The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-term observations are limited., Methods: Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored., Results: During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors., Conclusions: This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: We designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS)., Methods: Patients with IMN were divided into 2 groups, and MZR combined with PSL was administered for 2 years. PSL was initially prescribed at 40 mg/day and tapered. MZR was given once-a-day at 150 mg and 3-times-a-day at 50 mg each to groups 1 and 2. Serum MZR concentrations from 0 to 4 h after administration were examined within one month of treatment. The concentration curve and peak serum level (C max ) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR., Results: At 2 years, 10 of 19 patients (52.6 %) in group 1 and 7 of 18 patients (38.9 %) in group 2 achieved complete remission (CR). The time-to-remission curve using the Kaplan-Meier technique revealed an increase in the cumulative CR rate in group 1, but no significant difference between the groups. Meanwhile, there was a significant difference in C max between groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 μg/mL, p = 0.04), and C max levels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that C max more than 1.1 µg/mL was necessary for CR in once-a-day administration., Conclusion: Administration of MZR once a day is useful when combined with PSL for treatment of IMN with SRNS. In addition, it is important to assay the serum concentration of MZR and to determine C max , and more than 1.1 µg/mL of C max is necessary for CR.

Background: Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites., Methods: NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed., Results: NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed mesangial proliferative glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection., Conclusion: The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.

Background: The mortality and morbidity associated with acute kidney injury (AKI) remains high, despite advances in interventions. A multifunctional heparin-binding growth factor, midkine (MK), is involved in the pathogenesis of ischemic kidney injury. However, the clinical relevance of MK has not yet been elucidated. The present study investigated whether urinary MK can serve as a novel biomarker of AKI., Methods: We initially compared the predictive value of MK with other urinary biomarkers, including N-acetyl-β-D-glucosaminidase (NAG), interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL), for the detection and differential diagnosis of established AKI (549 patients). Subsequently, the reliability of MK for the early detection of AKI was prospectively evaluated in 40 patients undergoing elective abdominal aortic aneurysm surgery. Urine samples were obtained at baseline, the period of aortic cross-clamping and declamping, the end of the surgery, and on post-operative day 1., Results: The areas under the receiver operating characteristic curves for the diagnosis of AKI in various kidney diseases were 0.88, 0.70, 0.72, and 0.84 for MK, NAG, IL-18, and NGAL, respectively. When the optimal cutoff value of urinary MK was set at 11.5 pg/mL, the sensitivity and specificity were 0.87 and 0.85, respectively. In the second study, urinary MK peaked at the period of aortic declamping, about 1 h after cross-clamping in patients with AKI. Interestingly, the rise of MK in AKI patients was very precipitous compared with other biomarker candidates., Conclusion: Urinary MK was prominent in its ability to detect AKI and may allow the start of preemptive medication.

Fungal peritonitis in a patient on peritoneal dialysis (PD) is a refractory injury accompanied by severe inflammation, predisposing patients to a poor prognosis. Defective clearance of necrotic tissue interferes with amelioration of tissue injury and induces abnormal tissue remodeling. In the recent reports, apoptosis inhibitor of macrophage (AIM, also called CD5L) prevents obesity, hepatocellular carcinoma and acute kidney injury. Here, we investigated potential roles of AIM in prevention of progression of fungal peritonitis models. AIM -/- mice subjected to zymosan-induced peritonitis exhibited progressive inflammation and sustained peritoneal necrosis tissue on day 28 after the disease induction, whereas there was an improvement in AIM +/+ mice. This appeared to be caused by deposition of AIM at the necrotic peritoneum in AIM +/+ mice. In vitro, AIM enhanced the engulfment of necrotic debris by macrophages derived from zymosan-induced peritonitis, M1- and M2a-like bone marrow derived macrophages, as well as by mesothelial cells. In addition, administration of recombinant AIM dramatically ameliorated severe inflammation associated with necrosis in zymosan-induced peritonitis of AIM -/- mice. Our observations suggest that AIM appears to be involved in the repair process of zymosan-induced peritonitis, and thus, could be the basis of development of new therapeutic strategies for PD-related fungal peritonitis.

There are two different Japanese serum creatinine-based equations for estimated glomerular filtration rate (eGFR), for adults and paediatric patients, with both equations deemed applicable to 18-year-old subjects. This study assessed the relative accuracy of the two equations in assessing eGFR in patients aged 18 years with chronic kidney disease. A total of 3042 patients (1679 males and 1363 females), aged 2-20 years, who were registered in the Japan Renal Biopsy Registry or the Japan Kidney Disease Registry between 2007 and 2013 were evaluated. eGFR values derived from formulas for children (Uemura's formula) and adults (the 3-variable Japanese formula) were calculated and compared, especially in patients aged 18 years. At all ages, but especially at younger ages, eGFR was significantly higher when calculated with the adult than the paediatric formula. This finding was also observed in 18-year-old adolescents with eGFR <90 mL/min per 1.73 m 2 (P = 0.026). However, the mean difference between the two calculated eGFRs was only 2.79 mL/min per 1.73 m 2 . These findings indicate that both creatinine-based equations used to calculate eGFR rate in Japanese children and adults with chronic kidney disease could be used to determine eGFR in 18-year-old subjects, with the difference between the two within permissible levels for clinical use., (© 2017 Asian Pacific Society of Nephrology.)

Background: Chronic kidney disease (CKD) eventually progresses to end-stage renal disease (ESRD). However, risk factors associated with CKD progression have not been well characterized in Japanese patients with CKD who are less affected with coronary disease than Westerners., Methods: A large-scale, multicenter, prospective, cohort study was conducted in patients with CKD and under nephrology care, who met the eligibility criteria [Japanese; age 20-75 years; and estimated glomerular filtration rate (eGFR): 10-59 mL/min/1.73 m 2 ]. The primary endpoint was a composite of time to a 50 % decline in eGFR from baseline or time to the initiation of renal replacement therapy (RRT). The secondary endpoints were the rate of decline in eGFR from baseline, time to a 50 % decline in eGFR from baseline, time to the initiation of RRT, and time to doubling of serum creatinine (Cre) concentration., Results: 2966 patients (female, 38.9 %; age, 60. 3 ± 11.6 years) were enrolled. The incidence of the primary endpoint increased significantly (P < 0.0001) in concert with CKD stage at baseline. The multivariate Cox proportional hazards models revealed that elevated systolic blood pressure (SBP) [hazard ratio (HR) 1.203, 95 % confidence interval (CI) 1.099-1.318)] and increased albumin-to-creatinine ratio (UACR ≥ 1000 mg/g Cre; HR: 4.523; 95 % CI 3.098-6.604) at baseline were significantly associated (P < 0.0001, respectively) with the primary endpoint., Conclusions: Elevated SBP and increased UACR were risk factors that were significantly associated with CKD progression to ESRD in Japanese patients under nephrology care. UMIN clinical trial registry number: UMIN000020038.

Background: Blood pressure is influenced by hereditary factors and dietary habits. The objective of this study was to examine the effect of dietary salt consumption and single-nucleotide polymorphisms (SNPs) on blood pressure (BP)., Methods: This was a cross-sectional analysis of 2728 male participants who participated in a health examination in 2009. Average dietary salt consumption was estimated using electronically collected meal purchase data from cafeteria. A multivariate analysis, adjusting for clinically relevant factors, was conducted to examine whether the effect on BP of salt consumption, SNPs, and interaction between salt consumption and each SNP. This study examined the SNPs AGT rs699 (Met235Thr), ADD1 rs4961 (Gly460Trp), NPPA rs5063 (Val32Met), GPX1 rs1050450 (Pro198Leu), and AGTR1 rs5186 (A1166C) in relation to hypertension and salt sensitivity., Results: BP was not significantly associated with SNPs or salt consumption. The interaction between salt consumption and SNPs with systolic BP showed a significant association in NPPA rs5063 (Val32Met) (P = 0.023) and a marginal trend toward significance in rs4961 and rs1050450 (P = 0.060 and 0.067, respectively)., Conclusion: The effect of salt consumption on BP differed by genotype. Dietary salt consumption and genetic variation can predict a high risk of hypertension.

Background: Microscopic polyangiitis (MPA), which is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis, is one of the most frequent primary vasculitides in Japan. We earlier nominated 16 genes (IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2) as predictors of response to remission induction therapy against MPA. The aim of this study is to determine the accuracy of prediction using these 16 predictors., Methods: Thirty-nine MPA patients were selected randomly and retrospectively from the Japanese nationwide RemIT-JAV-RPGN cohort and enrolled in this study. Remission induction therapy was conducted according to the Guidelines of Treatment for ANCA-Associated Vasculitis published by the Ministry of Health, Labour, and Welfare of Japan. Response to remission induction therapy was predicted by profiling the altered expressions of the 16 predictors between the period before and 1 week after the beginning of treatment. Remission is defined as the absence of clinical manifestations of active vasculitis (Birmingham Vasculitis Activity Score 2003: 0 or 1 point). Persistent remission for 18 months is regarded as a "good response," whereas no remission or relapse after remission is regarded as a "poor response.", Results: "Poor" and "good" responses were predicted in 7 and 32 patients, respectively. Five out of 7 patients with "poor" prediction and 1 out of 32 patients with "good" prediction experienced relapse after remission. One out of 7 patients with "poor" prediction was not conducted to remission. Accordingly, the sensitivity and specificity to predict poor response was 85.7% (6/7) and 96.9% (31/32), respectively., Conclusions: Response to remission induction therapy can be predicted by monitoring the altered expressions of the 16 predictors in the peripheral blood at an early point of treatment in MPA patients.

Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells. Macrophage infiltration in the peritoneal wall (P<0.001), heart (P<0.05) and para-aortic tissues (P<0.001) was significantly higher in 5/6Nx with salt loading (5/6Nx/NaCl) than in 5/6Nx without salt loading (5/6Nx/Water); however, there were no significant differences in blood pressure and renal function between the groups. Tissue interleukin-6, monocyte chemotactic protein-1 (MCP-1), serum- and glucocorticoid-inducible kinase 1 (Sgk1) and tonicity-responsive enhancer binding protein (TonEBP) mRNA were significantly elevated in the peritoneal wall and heart with 5/6Nx/NaCl when compared with 5/6Nx/Water. Sodium was stored in the abdominal wall, exerting high-osmotic conditions. Reversal of salt loading reduced macrophage infiltration associated with decreased TonEBP in 5/6Nx/NaCl. Macrophage infiltration associated with fibrosis induced by salt loading was decreased in the 5/6Nx/NaCl/CC chemokine receptor 2 (CCR2, receptor of MCP-1)-deficient mice when compared with 5/6Nx/NaCl/Wild mice, suggesting that CCR2 is required for macrophage infiltration in 5/6Nx with NaCl loading. In cultured mesothelial cells and cardiomyocytes, culture media with high NaCl concentration induced MCP-1, Sgk1 and TonEBP mRNA, all of which were suppressed by TonEBP siRNA, indicating that both MCP-1 and Sgk1 are downstream of TonEBP. Our study indicates that high NaCl intake induces MCP-1 expression leading to macrophage infiltration via the TonEBP-MCP-1 pathway in 5/6Nx/NaCl mice, and that TonEBP has a central role in inflammation in patients with renal failure taking high salt.

Background/aims: The Oxford classification of IgA nephropathy (IgAN) was proposed by international working group in 2009. Interobserver reproducibility of each pathological definition was already evaluated, but that of four pathological prognostic parameters score has not yet been assessed. We first assess the reproducibility of each pathological definition in Japanese patients. Our study is aimed to assess that of four pathological prognostic parameters score among the five Japanese pathologists., Methods: The renal specimens from 411 Japanese patients, aged 3-85 years, with biopsied proven primary IgAN were collected from 50 facilities between 2006 and 2012. The reproducibility of pathological definitions was assessed by the intraclass correlation coefficient (ICC) and that of four pathological prognostic parameters score (mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T)) was assessed by kappa statistics., Results: The ICC of M, E, S, T, global sclerosis and cellular crescents and/or fibrocellular crescents were good or moderate agreement among the five pathologists and were well agreed with results of the Oxford study. Kappa statistics was moderate agreement for M and T score assessed with the semi-quantitative method by the Oxford group, but that was poor agreement for S and E score based on a simple "present" or "absent" assessment., Conclusion: This is the first report to assess the reproducibility of pathological prognostic parameters score in the Oxford classification. Our study supports the utilization of the pathological lesions in routine diagnosis. The methodological assessment of pathological prognostic parameters score should be reconsidered.

Background: We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis., Methods: We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF., Results: When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms., Conclusion: Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis., Competing Interests: The authors have declared that no competing interests exist.