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

Abstract

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. We included adult nephrotic patients with Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD) who received immunosuppressive therapy (IST) in a North American (NEPTUNE, n=89) or Japanese (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. NEPTUNE cases had more FSGS (53.9 vs. 17.0%) and family history of kidney disease (35.2 vs. 3.2%). N-KDR cases were older (median 56 vs. 43 years) and demonstrated greater levels of UPCR (7.73 vs. 6.65) and hypoalbuminemia (1.6 vs. 2.2 mg/dL). N-KDR cases showed higher proportion of CR (overall: 89.2 vs. 62.9%; FSGS: 67.3 vs. 43.7%; MCD: 93.7 vs. 85.4%). A multivariable model showed that FSGS (vs. MCD: HR=0.28, 95%CI 0.20-0.41), systolic blood pressure (per 10 mmHg: HR=0.93, 95%CI 0.86-0.99) and eGFR (per 10 mL/min/1.73m2: HR=1.16, 95%CI 1.09-1.24) were associated with time to CR. There were significant interactions in patient age (p=0.004) and eGFR (p=0.001) between the cohorts. 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 multi-national clinical trials.