Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective

Abstract

Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular injury, rather than a single disease, that is caused by diverse clinicopathological entities with different mechanisms of injury with the podocyte as the principal target of lesion, leading to the characteristic sclerotic lesions in parts (i.e., focal) of some (i.e., segmental) glomeruli. The lesion of FSGS has shown an increasing prevalence over the past few decades and is considered the most common glomerular cause leading to ESKD. Primary FSGS, which usually presents with nephrotic syndrome, is thought to be caused by circulating permeability factors that have a main role in podocyte foot process effacement. Secondary forms of FSGS include maladaptive FSGS secondary to glomerular hyperfiltration such as in obesity or in cases of loss in nephron mass, virus-associated FSGS, and drugassociated FSGS that can result in direct podocyte injury. Genetic FSGS is increasingly been recognized and a careful evaluation of patients with atypical primary or secondary FSGS should be performed to exclude genetic causes. Unlike primary FSGS, secondary and genetic forms of FSGS do not respond to immunosuppression and tend not to recur after kidney transplantation. Distinguishing primary FSGS from secondary and genetic causes has a prognostic significance and is crucial for an appropriate management. In this review, we examine the pathogenesis, clinical approach to distinguish between the different causes, and current recommendations in the management of FSGS.

Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study

“…AS can mimic focal segmental glomerulosclerosis (FSGS) and accounts for almost 3% of cases of chronic kidney disease (CKD) [ 2 ]. Variants in the slit-diaphragm genes NPHS1 and NPHS2, as well as INF2, are other classical hereditary causes of FSGS in adolescents and young adults [ 2 , 3 ]. In these hereditary diseases of the glomerular filtration barrier, angiotensin-converting-enzyme inhibitors (ACEis) have evolved as the cornerstone of treatment, starting pre-emptively in oligo-symptomatic toddlers with isolated micro-hematuria [ 4 , 5 ].…”

Identification of Genetic Causes of Focal Segmental Glomerulosclerosis Increases With Proper Patient Selection

“…4,5 Currently, FSGS is divided into primary, secondary, and genetic forms. [6][7][8][9] Such distinction is important because it has both prognostic and therapeutic implications. 7,8 Genetic forms of FSGS may happen sporadically or be familial and are caused by variants in genes that encode proteins that are expressed in either podocytes or the glomerular basement membrane (GBM).…”

The Transition From Minimal Change Disease to Focal and Segmental Glomerulosclerosis in a Patient With Nephrotic Syndrome: a Case Report

“…Irreversible glomerular damage caused in the context of FSGS can be explained by podocyte depletion. Compensatory hypertrophy of the remaining podocytes, cell-to-cell propagation of podocyte injury, and segmental solidi cation of the glomerular tuft can lead to progressive focal and segmental sclerosis [5,9].…”

“…Active treatment can achieve complete remission, rarely progression to end-stage renal disease(ESRD). Nephrotic syndrome due to FSGS can appear at any age, taking place in approximately 7-10% of children and 20-30% of adults [5]. Unlike MCD, more FSGS patients are resistant to corticosteroids.…”