Fig 1.
Flow diagram of patient selection in the present study.
Among 172 patients who were diagnosed with FSGS or minor glomerular abnormality with segmental glomerular lesions, adult cases with first episode of nephrotic syndrome who received immunosuppressive treatment were eligible for pathological review. The pathological review classified the patients into two groups: Typical FSGS, with typical segmental lesions according to the Columbia classification, and unclassified group, without such lesions. Patients in the typical FSGS group were categorized into five subgroups of histopathological variants of the Columbia classification. Patients in the unclassified group were categorized into three subgroups: “endothelial damage”, “simple attachment”, and “minor cellular lesion”. * Non-nephrotic cases included 26 patients whose etiologies were recorded: obesity (n = 15), hypertension (n = 7), unilateral kidney (n = 2), low birth weight (n = 1) and vesicoureteral reflux (n = 1). † Secondary cases: HIV infection (n = 1), genetic mutation (n = 1). ‡ Other glomerular diseases in pathological review: Nephrosclerosis (n = 1) and mesangial proliferative glomerulonephritis (n = 1). § Definitions of unclassified group are shown in Fig 2. Abbreviations: FSGS, Focal segmental glomerulosclerosis; NS, Nephrotic syndrome; COL, Collapsing variant; TIP, Tip variant; CEL, Cellular variant; PH, Perihilar variant; NOS, Not otherwise specified.
Fig 2.
Pathological findings in patients who did not fit any of the FSGS variants in the Columbia classification: The unclassified group.
(A and B) Typical finding of “endothelial damage” by PAM staining. The patients had findings suggesting endothelial damage, i.e., mesangiolysis and/or double contour of the glomerular basement membrane without endocapillary occlusion or matrix accumulation. (C and D) The finding of “simple attachment” by PAM staining. The image indicates small fibrous synechia to the Bowman capsule without any endocapillary or extracapillary interactions. The patients had no other findings on FSGS. (E and F) The finding of “minor cellular lesion” by PAM staining. The image indicates cellular occlusion of the glomerular capillaries by foam cell(s), but with a distribution of less than 25% of the tuft. The patients had no other findings on FSGS. A, C, and E are at ×400 magnification with PAM staining, and B, D, and F are at ×1000 magnification with PAM staining. Abbreviations: FSGS, Focal segmental glomerulosclerosis; PAM, Periodic acid methenamine silver stain.
Table 1.
Baseline characteristics of the subgroups.
Table 2.
Pathological findings of the subgroups.
Fig 3.
Outcome evaluation among typical variants of FSGS vs. unclassified group and their subgroups.
(A and B) Kaplan-Meier analysis for cumulative probability of complete remission. There were no significant differences between the typical FSGS group and the unclassified group (A). Among the subgroups, TIP and “simple attachment” had the best therapeutic reactivity. CEL and “endothelial damage” showed moderate response to immunosuppressive treatment (B). (C) Kaplan-Meier curve for 30% decline of eGFR. No significant differences were observed in comparison between the typical FSGS group and the unclassified group and comparison among the subgroups (S2 Fig). Abbreviations: FSGS, Focal segmental glomerulosclerosis; CEL, Cellular variant; TIP, Tip variant; NOS, Not otherwise specified; eGFR, Estimated glomerular filtration ratio.
Table 3.
Details of immunosuppressive treatment and outcomes of the subgroups.