Collapsing focal segmental glomerulosclerosis: Current concepts

Abstract

Collapsing focal segmental glomerulosclerosis (cFSGS), also known as collapsing glomerulopathy is currently classified under the rubric of FSGS. However, its defining morphological features are in stark contrast to those observed in most other variants of FSGS. During the early stage of the disease, the lesion is characterized pathologically by an implosive segmental and/or global collapse of the glomerular capillary tufts, marked hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial disease. With advancement of the disease, segmental and/or global glomerulosclerosis is also observed in association with the collapsing lesions. The etiology of this enigmatic disorder is still elusive, but a growing list of diseases/conditions is being reported in association with this morphological pattern of renal parenchymal injury. The pathogenesis of cFSGS involves discreet epithelial cell injury leading to cell cycle dysregulation and a proliferative cellular phenotype. From the clinical perspective, cFSGS is notorious for its propensity to affect black people, a high incidence and severity of nephrotic syndrome, marked resistance to empirical therapy, and rapid progression to end-stage renal disease. The lesion has also been reported in transplanted kidneys either as recurrent or de novo disease, frequently leading to graft loss. Most cases have been reported in western countries, but the lesion is also being increasingly recognized in the tropical regions. The recent increase in reporting of cFSGS partly reflects a true increase in the incidence and partly a detection bias. There is no specific treatment for the disorder at present. Newer insights into the pathogenesis may lead to the development of targeted and specific therapy in near future. There is an urgent need to increase awareness of the lesion among pathologists and nephrologists, especially those from developing countries, to ensure accurate diagnosis and appropriate managment. With the accumulation of more and more data, it is hoped that the prevailing confusion about the nosological identity of the lesion will also be resolved in a more logical way.

Keywords: Collapsing focal segmental glomerulosclerosis; End-stage renal disease; Etiology; Pathology; Prognosis; Renal biopsy.

Figure 1

High magnification view showing global collapse of capillary tufts associated with marked hypertrophy and hyperplasia of podocytes (arrow), forming a pseudo-crescent. Marked cytoplasmic vacuolization and protein resorption droplets (arrowhead) are seen in podocytes. Jones’ methenamine silver, × 400.

Figure 2

Medium-power view showing marked tubular atrophy associated with interstitial fibrosis and mononuclear inflammatory cell infiltrate in the interstitium. Many dilated tubules contain eosinophilic casts. One glomerulus shows ischemic solidification and another one, global collapse with podocyter hypertrophy but little podocyte proliferation (arrow). Jones’ methenamine silver, × 200.