Clinicopathological Characteristics of Obesity-associated Focal Segmental Glomerulosclerosis

Obesity-related glomerulopathy (ORG) is a secondary form of focal segmental glomerulosclerosis (FSGS) occurring in obese patients with a body-mass index higher than 30 kg/m(2). It is typically manifested by nephrotic-range proteinuria without full nephrotic syndrome, and progressive renal insufficiency. Characteristic morphologic features include the consistent presence of glomerulomegaly, predominance of perihilar variant of FSGS, and the relatively mild fusion of visceral epithelial cell foot processes. The concept of podocyte depletion as a driver of the glomerular scarring in obesity-associated FSGS is well documented. The underlying mechanisms are likely to be related in part to the oxidative stress and the impairment of the integrity of the slit diaphragm and cell adhesion resulting mainly from angiotensin II and transforming growth factor-beta. These proapoptotic cytokines are upregulated in obesity in response to insulin resistance, compensatory hyperinsulinemia and glomerular hyperfiltration-hypertension mediated mechanical stress. This review is designed to discuss the clinicopathologic features of obesity-associated FSGS, with a focus on the podocyte injury, which is involved in the onset and progression of the glomerulosclerotic process. Ultrastructural glomerular lesions are documented.