Collapsing Glomerulopathy: The Expanding Etiologic Spectrum of a Shrinking Glomerular Lesion

Abstract

Collapsing glomerulopathy (CG) is a relatively recently described pattern of renal parenchymal injury that is being increasingly recognized as a common cause of end-stage renal disease (ESRD) throughout the world (Albaqumi et al., 2006). Although, it is currently classified officially as one of the pathological variants of focal segmental glomerulosclerosis (FSGS), its defining morphological alterations are in marked contrast to those observed in other variants of FSGS. During the initial stages of the disease, the lesion is characterized morphologically by an implosive, segmental and/or global wrinkling and retraction of the glomerular capillary tufts, pronounced hypertrophy and proliferation of the visceral epithelial cells (VECs) or podocytes, and severe tubulointerstitial damage. With disease progression, segmental and/or global glomerulosclerosis is also observed in addition to the pathognomonic collapsing lesions. Often, both the active and chronic lesions (collapsing and sclerotic) co-exist at the time of pathologic diagnosis, hence its classification as a variant of FSGS (Albaqumi et al., 2006; Albaqumi & Barisoni, 2006). The exact cause of this mysterious lesion is still not known, but a growing list of both genetic and acquired diseases/conditions is being reported in association with this morphologic pattern of renal parenchymal injury (Albaqumi et al., 2006). The pathogenesis of CG is also still incompletely understood, but many advances have been made during the past two to three decades, especially in the development and study of animal models of the disease and the discovery of genetic abnormalities leading to CG. Various triggering agents typically cause discreet epithelial cell injury in different anatomical compartments of the renal parenchyma leading to cell cycle dysregulation and a proliferative cellular phenotype (Albaqumi et al., 2006; Albaqumi & Barisoni, 2006; Schwimmer et al., 2003). Clinically, CG is characterized by its black racial predilection, a high incidence and severity of nephrotic syndrome (NS), a poor response to the currently used empirical therapy, and a rapid downhill course to ESRD (Albaqumi & Barisoni, 2006; Schwimmer et al., 2003). Although most of the early studies were reported in the native kidneys, the disease has also been found more recently to afflict the transplanted kidneys, either as a recurrent or de novo disease, frequently leading to loss of the allograft (Schwimmer et al., 2003; Canaud et al., 2010; Gupta et al., 2011; Nadasday et al., 2002; Stokes et al., 1996; Swaminathan et al., 2006). Most of the cases have been reported from the western countries, but the lesion is also being increasingly recognized in the tropical regions