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Introduction: Disease subtyping and monitoring are essential for the management of nephrotic syndrome (NS). Although various biomarkers for NS have been reported, their clinical efficacy has not been comprehensively validated in adult Japanese patients. Methods: The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN). Baseline clinical information and plasma and urine samples will be collected at the time of immunosuppressive therapy initiation or biopsy. Follow-up data and plasma and urine samples will be collected longitudinally based on the designated protocols. Candidate biomarkers will be measured: CD80, cytotoxic T-lymphocyte antigen 4, and soluble urokinase plasminogen activator receptor for MCD and FSGS; anti-phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A antibodies for MN; fragment Ba, C3a, factor I, and properdin for MPGN/C3G; and CD11b, CD16b, and CD163 for LN. Outcomes include complete and partial remission, relapse of proteinuria, a 30% reduction in estimated glomerular filtration rate (eGFR), eGFR decline, and initiation of renal replacement therapy. The diagnostic accuracy and predictive ability for clinical outcomes will be assessed for each biomarker. Results: From April 2019 to April 2023, 365 patients were enrolled: 145, 21, 138, 10, and 51 cases of MCD, FSGS, MN, MPGN/C3G, and LN, respectively. Conclusion: This study will provide valuable insights into biomarkers for NS and serve as a biorepository for future studies. [ABSTRACT FROM AUTHOR]

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse. [ABSTRACT FROM AUTHOR]

Introduction: Albeit uncommon, hydrothorax is an important complication of peritoneal dialysis (PD). Due to paucity of evidence for optimal treatment, this study aimed to evaluate the effectiveness and safety of computed tomographic (CT) peritoneography and surgical intervention involving video-assisted thoracic surgery (VATS) for hydrothorax in a retrospective cohort of patients who underwent PD in Japan. Methods: Of the 982 patients who underwent PD from six centers in Japan between 2007 and 2019, 25 (2.5%) with diagnosed hydrothorax were enrolled in this study. PD withdrawal rates were compared between patients who underwent VATS for diaphragm repair (surgical group) and those who did not (non-surgical group) using the Kaplan-Meier method and log-rank test. Results: The surgical and non-surgical groups comprised a total of 11 (44%) and 14 (56%) patients, respectively. Following hydrothorax diagnosis by thoracentesis and detection of penetrated sites on the diaphragm using CT peritoneography, VATS was performed at a median time of 31 days (interquartile range [IQR], 20–96 days). During follow-up (median, 26 months; IQR, 10–51 months), 9 (64.3%) and 2 (18.2%) patients in the non-surgical and surgical groups, respectively, withdrew from PD (P = 0.021). There were no surgery-related complications or hydrothorax relapse in the surgical group. Conclusions: This study demonstrated the effectiveness and safety of CT peritoneography and VATS for hydrothorax. This approach may be useful in hydrothorax cases to avoid early drop out of PD and continue PD in the long term. Further studies are warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Over 300,000 patients receive maintenance dialysis in Japan; managing these patients is extremely important. This study aimed to report on prior management of chronic kidney diseases and prognostication after dialysis initiation. Patients and methods: Seventeen institutions participated in the Aichi cohort study of prognosis in patients newly initiated into dialysis and recruited patients over a period of 2 years. Exclusion criteria were (1) patients under 20 years; (2) patients who died before hospital discharge; and (3) patients who could not provide consent. Result: Here, we showed data on dialysis initiation time. Of 1524 patients with mean age of 67.5 ± 13.0 years, 659 patients were put on dialysis following diabetic nephropathy diagnosis. At dialysis initiation time, creatinine and estimated glomerular filtration rate levels were 8.97 ± 3.21 mg/dl and 5.45 ± 2.22 ml/min/1.73 m, respectively. Medications taken were angiotensin II receptor blockers in 866; angiotensin-converting enzyme inhibitors in 135; calcium antagonist in 1202; and diuretics, alone or in combination, in 1059. Among patients with diabetic nephropathy, many had increased body weight and systolic blood pressure and were taking loop and thiazide diuretics at dialysis initiation time. Many patients with diabetic nephropathy had coronary artery disease and percutaneous coronary intervention. Conclusion: Many patients with diabetic nephropathy who registered for this study had coronary artery disease and problems with excess body fluid. Further analyses may clarify how underlying conditions and disease management before and after dialysis initiation affect prognosis. [ABSTRACT FROM AUTHOR]

Background: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items., Methods: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood., Results: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort., Conclusions: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome., (© 2022. The Author(s).)

Background: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse., Methods: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors., Results: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively)., Conclusion: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: A Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown a one-to-one male-to-female mortality ratio, notwithstanding the statistically longer life expectancy of women in the general population. This finding contrasts with the recent report that Japanese women on dialysis treatment have a more favorable longevity. Accordingly, we further investigated the clinical procedures and outcomes to clarify the sex differences in Japanese patients undergoing dialysis treatment., Methods: Subjects were incident dialysis patients who participated in a multicenter prospective cohort study from October 2011 to September 2013. The all-cause mortality was analyzed by a Cox proportional hazard regression model and studied separately in women and men with or without cardiovascular disease (CVD) at baseline., Results: Overall, 492 (32.3%) of the 1520 test subjects were women. All-cause mortality was higher in men (28.6%) than in women (19.9%, p < 0.001). Female sex (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.54-0.90) and history of CVD (HR: 1.51, 95% CI: 1.18-1.95) were independent predictors of all-cause mortality. In patients without CVD, female gender was strong independent contributor (HR = 0.46, 95% CI: 0.30-0.70, p < 0.001). In contrast, patients with CVD showed no difference in survival between the sexes (HR: 0.92, 95% CI: 0.67-1.24, p = 0.597)., Conclusion: Our study demonstrated that women undergoing chronic dialysis therapy had a lower mortality risk than men. However, complication with CVD canceled out the survival advantage in Japanese women on chronic dialysis. We should reevaluate the risk of women with CVD undergoing dialysis and apply the optimal care for CVD., (© 2021. Japanese Society of Nephrology.)

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: 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.