Collapsing Glomerulopathy: A Review by the Collapsing Brazilian Consortium

Abstract

Collapsing glomerulopathy (CG) is a clinicopathologic entity characterized by segmentar or global collapse of the glomerulus and hypertrophy and hyperplasia of podocytes. The Columbia classification of 2004 classified CG as a histological subtype of focal segmental glomerulosclerosis (FSGS). A growing number of studies have demonstrated a high prevalence of CG in many countries, especially among populations with a higher proportion of people with African descent. The present study is a narrative review of articles extracted from PubMed, Medline, and Scielo databases from September 1, 2020 to December 31, 2021. We have focused on populational studies (specially cross-sectional and cohort articles). CG is defined as a podocytopathy with a distinct pathogenesis characterized by strong podocyte proliferative activity. The most significant risk factors for CG include APOL1 gene mutations and infections with human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. CG typically presents with more severe symptoms and greater renal damage. The prognosis is notably worse than that of other FSGS subtypes.

Keywords: glomerulopathy; nephrotic syndrome (NS); podocytes; renal biopsy; segmental and focal glomerulosclerosis.

FIGURE 1

Glomerular pattern and podocytes morphological changes in human podocytopathies (bar = 10 μm).

FIGURE 2

Collapsing glomerulopathy etiologies.

FIGURE 3

Kidney biopsies of collapsing glomerulopathy. (A,B) Periodic Acid Schiff (PAS) and Jones Methenamine Silver (JMS) (40×), respectively show intense podocyte hyperplasia and glomerular tuft collapse. (C) JMS (20×) exhibits microcytic transformation of distal convoluted tubules with accumulations of hyaline material inside of those. (D,E) Fluorescence microscopy (40×) shows, respectively, IgM and C3 trapping in areas of collapse/sclerosis. (F) Semi-fine stained in Toluidine Blue (63×) with collapse of the entire glomerular tuft and hyperplasia of podocytes and dilated Bowman’s space. (G,H) Transmission electron microscopy contrasted with Osmium Tetroxide, Lead Citrate and Uranyl in block shows capillary loop collapse with hyalinosis in addition to diffuse fusion and flattening of the pedicels associated with microvillous transformation. (I) Electron microscopy tubes contrasted with osmium tetroxide, lead citrate, and uranyl in block with detail of disorganization of the cytoskeleton in the podocyte cytoplasm, with extensive effacement of the pedicels.