Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants

Abstract

Histologic variants of idiopathic focal segmental glomerulosclerosis (FSGS) may have prognostic value. A recent working classification system has distinguished five FSGS variants. We evaluated a cohort of adult patients with biopsy-proven FSGS diagnosed between March 1982 and July 2001 to determine if subtypes were associated with renal outcome. Renal biopsies were reviewed by two pathologists. Demographic and clinical data were obtained from charts. Outcomes were partial and complete remission of the nephrotic syndrome, and renal failure. The frequency of FSGS variants was: 3% cellular (N=6), 11% collapsing (N=22), 17% tip lesion (N=34), 26% perihilar (N=52), and 42% not otherwise specified (NOS) (N=83). Collapsing FSGS affected younger and more often black patients. Black race was uncommon in tip variant. Collapsing and tip variants had higher proteinuria and lower serum albumin than perihilar and NOS variants. Better renal function and less severe tubulointerstitial injury were observed in patients with tip variant. These patients were more likely to receive steroids and more often achieved complete remission (50%). After a median follow-up of 1.8 years, 23% of patients were on dialysis and 28% had renal failure. Collapsing FSGS had worse 1-year (74%) and 3-year (33%) renal survival compared to other variants (overall cohort renal survival at 1 and 3 years: 86 and 67%). Different histologic variants of FSGS have substantial differences in clinical features at the time of biopsy diagnosis and substantial differences in renal outcomes.

Association of Histologic Variants in FSGS Clinical Trial with Presenting Features and Outcomes

“…This study identified NOS as the most common subtype, comprising 68% of this cohort, followed by collapsing (12%), tip (10%), perihilar (7%), and cellular variants (3%) (4,5). In comparison, FSGS subtyping at Columbia University showed 62.3% NOS or perihilar variants, 23.7% collapsing, 9.4% tip, and 4.5% cellular variants (4).…”

“…The FSGS-CT findings support significant differences in demographic features between histologic subtypes. Tip and collapsing variants were more common in teenagers and adults than children (5,6,12,(14)(15)(16)(17)(18)(19). Only 29% of tip patients were children aged 2-12 years at onset of FSGS, whereas 43% were over 18 years.…”

“…Often referred to as the Columbia classification, this schema was chosen for renal biopsy analysis within the FSGS-CT (3). This histologic approach has been shown to differentiate presenting clinical features and outcomes in several nonrandomized retrospective studies (4,5). Some investigators have argued that achievement of complete or partial remission of nephrotic syndrome is a better predictor of outcome in FSGS than the histologic variant (6).…”

Focal Segmental Glomerulosclerosis

“…The latter might be considered to include familial/genetic forms, virus-associated forms, drug-induced forms, and forms mediated by adaptive structural-functional responses (i.e., in the setting of congenital or acquired reduction of renal mass/nephron complement). Clinical response and prognosis may relate to the histologic variant, most notably the glucocorticioid responsiveness of the tip lesion and the aggressive, unrelenting nature of the collapsing variants (21,22). It is with this in mind that the variants are included in standard pathology reports.…”

Cellular Focal Segmental Glomerulosclerosis: A Controversial Pathological Entity. Its Pathogenesis and Therapeutic Basis

“…In other studies the cellular lesion is more frequent in African Americans when nephrotic and nonnephrotic patients with FSGS are included, but in patients with nephrotic range proteinuria, the difference is no longer significant. When we consider the Columbia classification cellular variant is the least frequent, representing 3% of the case [6]. If the criteria of the Columbia classification are applied to a pediatric population with a high prevalence of African Americans, the ratio between the different variants changes, increasing the percentage of cellular type (32%).…”