Collapsing Focal Segmental Glomerulosclerosis: A Morphological Lesion in Search of Nosologic Identity

Collapsing focal segmental glomerulosclerosis (cFSGS) is a distinct clinicopathological variant of focal segmental glomerulosclerosis (FSGS) characterized pathologically by the segmental and/or global collapse of the glomerular capillaries, marked hypertrophy and hyperplasia of visceral epithelial cells (VECs), and severe tubulointerstitial disease. The etiology of this lesion is still elusive, but a growing list of diseases/conditions is associated with this morphologic expression of renal parenchymal injury. The pathogenesis of cFSGS involves VEC injury leading to cell cycle dysregulation and a proliferative podocyte phenotype. Clinically, collapsing glomerulopathy is characterized by black racial predisposition, a high incidence and severity of nephrotic syndrome (NS), poor response to empirical therapy, and rapid progression to end-stage renal disease (ESRD). The lesion has also been reported in transplanted kidneys either as recurrent or de novo disease, often leading to loss of the allograft. Most of the cases have been reported from the western countries, but the lesion is being increasingly recognized in the tropics as well. The optimal treatment for cFSGS is still not known. Empirical therapies include steroids or cyclosporine in addition to aggressive blood pressure control, angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor blockers (ARBs), and lipid lowering agents. The role of other immunosuppressive agents such as mycophenolate mofetil in the treatment of cFSGS awaits further studies. Newer insights into the pathogenesis may change this ominous outlook for this therapeutically resistant form of FSGS. There is still lack of awareness among the pathologists and nephrologists in the developing countries about this lesion. There is an urgent need to educate the pathologists and nephrologists from developing countries on this topic. This review describes the historical background, epidemiology, etiology, pathogenesis, pathology, treatment, and prognosis of this disorder, with an emphasis on the pathologic features on renal biopsies to facilitate its accurate diagnosis in developing countries.