Autoimmunity in Focal Segmental Glomerulosclerosis: A Long-Standing Yet Elusive Association

Abstract

Focal segmental glomerulosclerosis (FSGS) is a histological term that describes a pathologic renal entity affecting both adults and children, with a wide array of possible underlying etiologies. Podocyte damage with scarring, the hallmark of this condition, leads to altered permeability of the glomerular barrier, which may result in massive proteinuria and relentless renal function deterioration. A definite cause of focal segmental glomerulosclerosis can be confirmed in a minority of cases, while most forms have been traditionally labeled as primary or idiopathic. Despite this definition, increasing evidence indicates that primary forms are a heterogenous group rather than a single disease entity: several circulating factors that may affect glomerular permeability have been proposed as potential culprits, and both humoral and cellular immunity have been implicated in the pathogenesis of the disease. Consistently, immunosuppressive drugs are considered as the cornerstone of treatment for primary focal segmental glomerulosclerosis, but response to these agents and long-term outcomes are highly variable. In this review we provide a summary of historical and recent advances on the pathogenesis of primary focal segmental glomerulosclerosis, focusing on implications for its differential diagnosis and treatment.

Hemizygous nonsense variant in the moesin gene (MSN) leads to a new autoimmune phenotype of Immunodeficiency 50

“…Secondary FSGS in P1 was ruled out by histology and clinical features, suggesting primary, immune-mediated FSGS ( 30 ). The effectiveness of glucocorticoids in our case and in many podocytopathies (kidney diseases in which direct or indirect podocyte injury drives proteinuria or nephrotic syndrome) suggests immune system-related pathogenesis of the kidney symptoms ( 31 ).…”

Pro-Inflammatory Profile of Adipokines in Obesity Contributes to Pathogenesis, Nutritional Disorders, and Cardiovascular Risk in Chronic Kidney Disease

“…Excessive production of these cells can lead to glomerulosclerosis through mesangial hypertrophy in the glomeruli, thickening of the glomerular basement membrane, and increased extracellular matrix [ 11 ]. In turn, glomerulosclerosis, by increasing the permeability of the glomerular barrier, contributes to proteinuria and impaired renal function [ 56 ].…”

Decay-Accelerating Factor Expression Modulates the Severity of Experimental Focal Segmental Glomerulosclerosis

“…Despite significant advances in the field, the molecular mechanisms that govern the disease pathophysiology are still incompletely understood, which severely limits therapeutic options. Current therapies based on generalized immunosuppression are effective in less than half of the patients, and persistence of nephrotic syndrome is associated with a relentless progression to kidney failure (2,3). These features make the treatment of primary FSGS a largely unmet medical need.…”