Clinical Course of Adult FSGS and Minimal Change Disease in North American and Japanese Cohorts

KEY POINTS: Data from different geographical regions highlighted the differences in clinical manifestations and treatment response of adult FSGS/minimal change disease. There were shared factors that were associated with treatment response across the cohorts: FSGS, higher BP, and lower eGFR. Recognizing geographical difference allows us better understanding of disease biology, risk prediction, and design of future clinical trials. BACKGROUND: Regional differences in presentation and clinical course of nephrotic syndrome (NS) have not been studied well because few studies directly compared the data from different intercontinental regions. METHODS: We included adult nephrotic patients with FSGS and minimal change disease (MCD) who received immunosuppressive therapy (IST) in a North American (Nephrotic Syndrome Study Network [NEPTUNE], N=89) or Japanese (Nagoya Kidney Disease Registry [N-KDR], N=288) cohort. Baseline characteristics and rates of complete remission (CR) were compared. Factors associated with time to CR were evaluated by Cox regression models. RESULTS: NEPTUNE participants had more FSGS (53.9 versus 17.0%) and family history of kidney disease (35.2 versus 3.2%). N-KDR participants were older (median 56 versus 43 years) and demonstrated greater levels of urine protein creatinine ratio (7.73 versus 6.65) and hypoalbuminemia (1.6 versus 2.2 mg/dl). N-KDR participants showed higher proportion of CR (overall: 89.2 versus 62.9%; FSGS: 67.3 versus 43.7%; MCD: 93.7 versus 85.4%). A multivariable model showed that FSGS (versus MCD: hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.20 to 0.41), systolic BP (per 10 mm Hg: HR, 0.93; 95% CI, 0.86 to 0.99), and eGFR (per 10 ml/min per 1.73 m(2): HR, 1.16; 95% CI, 1.09 to 1.24) were associated with time to CR. There were significant interactions in patient age (P = 0.004) and eGFR (P = 0.001) between the cohorts. CONCLUSIONS: The North American cohort had more FSGS and more frequent family history. Japanese patients showed more severe NS with better response to IST. FSGS, hypertension, and lower eGFR were shared predictors of poor treatment response. Identifying shared and unique features across geographically diverse populations may help uncover biologically relevant subgroups, improve prediction of disease course, and better design future multinational clinical trials.