Clinical manifestations of focal segmental glomerulosclerosis in Japan from the Japan Renal Biopsy Registry: age stratification and comparison with minimal change disease

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


Supplementary
. Overview of the histologically diagnosed "focal segmental glomerulosclerosis" in the J-RBR Supplementary Table S1. Details of the distribution of histopathologically diagnosed "focal segmental glomerulosclerosis" in the J-RBR Supplementary Figure S2. Overview of the histologically diagnosed "minor glomerular abnormalities" in the J-RBR Supplementary Table S2 Figure S1. Overview of the histologically diagnosed "focal segmental glomerulosclerosis" in the J-RBR Registration in the J-RBR system has 3 diagnostic components: (ⅰ) clinical diagnosis, (ⅱ) histological diagnosis by pathogenesis, and (ⅲ) histological diagnosis by histopathology. The details of diagnostic system in the J-RBR should be referred to Sugiyama H et al., Clin Exp Nephrol 2011;15493-503. From 30,949 patients who were registered to the J-RBR, 1,409 patients whose histological diagnosis by histopathology was "focal segmental glomerulosclerosis" were extracted for the analyses of FSGS. They included four types of patients as below.
Primary FSGS; Patients who were registered as "primary glomerular disease" in histological diagnosis (pathogenesis) without any information explaining the etiology of secondary cases. Secondary FSGS; Patients who were registered with any information regarding the etiology of FSGS. Patients in this group could be identified only when the case has been registered with optional information about etiology. FSGS lesion in other diseases; Patients with other type of systemic or glomerular diseases who had nonspecific segmental scarring, i.e. diabetic nephropathy, lupus nephritis and so on. Patients with any type of histological diagnosis (pathogenesis) except for "primary glomerular disease" were categorized to this group unless there were any information regarding secondary cases. Renal graft: Patients whose clinical diagnosis was "renal transplantation" or whose histological diagnosis (pathogenesis) was "transplanted kidney". *Patients whose histological diagnosis (pathogenesis) was "primary glomerular disease" were categorized to "Primary FSGS" in main analyses unless they had any information about the etiology of FSGS.

Supplementary
Patients who were registered with any information regarding the etiology of FSGS were categorized to "Secondary FSGS" in main analyses. †Patients whose histological diagnosis (pathogenesis) was "hypertensive nephrosclerosis" were categorized to "Secondary FSGS" as hypertension related FSGS in main analyses. ‡Patients whose histological diagnosis (pathogenesis) was "transplant kidney" were categorized to "Renal graft" and excluded from main analyses.
Patients who had any histological diagnosis (pathogenesis) except above were categorized to "FSGS in other diseases" and excluded from main analyses unless they had any information about the etiology of FSGS.
Abbreviations: J-RBR, Japan Renal Biopsy Registry; FSGS, focal segmental glomerulosclerosis Patients in the "Secondary FSGS" could be identified when the case has been registered with optional information about etiology.
Abbreviations: FSGS, focal segmental glomerulosclerosis; HIV, human immunodeficiency virus Supplementary Figure S2. Overview of the histologically diagnosed "minor glomerular abnormalities" in the J-RBR Registration in the J-RBR system has 3 diagnostic components: (ⅰ) clinical diagnosis, (ⅱ) histological diagnosis by pathogenesis, and (ⅲ) histological diagnosis by histopathology. The details of diagnostic system in the J-RBR should be referred to Sugiyama H et al., Clin Exp Nephrol 2011;15493-503. From 30,949 patients who were registered to the J-RBR, 3,637 patients whose histological diagnosis by histopathology was "minor glomerular abnormalities" were extracted for the analyses of MCD. They included four types of patients as below.
Primary MCD; Patients who were registered as "primary glomerular disease" in histological diagnosis (pathogenesis) without any information about the etiology. In this category, the patients whose clinical diagnosis was NS and who fulfilled the laboratory criteria for NS, were included to Analysis 2. Secondary MCD; Patients who were registered with any information regarding the etiology of MCD. Patients in this group could be identified when the case has been registered with optional information about etiology. MGA in other diseases; Patients with other type of systemic or glomerular diseases who had no specific glomerular findings on light microscopy i.e. thin basement membrane disease, lupus nephritis (class I) and so on. Patients with any type of histological diagnosis (pathogenesis) except for "primary glomerular disease" were categorized to this group unless there were any information regarding secondary cases.
Renal graft: Patients whose clinical diagnosis was "renal transplantation" or whose histological diagnosis (pathogenesis) was "transplanted kidney".
Abbreviations: MCD, minimal change disease; J-RBR, Japan Renal Biopsy Registry; NS, nephrotic syndrome; MGA, minor glomerular abnormalities *Patients whose histological diagnosis (pathogenesis) was "primary glomerular disease" were categorized to "Primary MCD" in main analysis unless they had any information about the etiology of MCD.
Patients who were registered with any information regarding the etiology of MCD were categorized to "Secondary MCD" in main analysis.
Patients who had any histological diagnosis (pathogenesis) except for "primary glomerular disease" were categorized to "MGA in other diseases" and excluded from main analysis unless they had any information about the etiology of MCD. †Patients whose histological diagnosis (pathogenesis) was "transplant kidney" were categorized to "Renal graft" and excluded from main analysis.