Steroids, cyclophosphamide, cyclosporine, tacrolimus, and mycophenolate mofetil are options.
Focal segmental glomerulosclerosis (FSGS) is not a single disease but a histologic pattern of renal damage that initially affects the glomerulus and its tubulointerstitium (Nat Clin Pract Nephrol. 2005;1:44-54). FSGS is a leading cause of nephrotic syndrome worldwide and may be found in up to 35% of nephrotic individuals.
The pathogenesis remains uncertain, and the identification of distinct variants of FSGS, including collapsing glomerulonephropathy and the glomerular tip lesion, illustrates the importance of classification of these glomerular lesions.
The diagnosis of FSGS is based on histopathologic findings, although the glomerular pathology may result from multiple different molecular or cellular processes and be unrelated to a particular disease. Histopathology alone is unlikely to predict the natural history of FSGS.
Important factors to consider in the treatment of FSGS include the identification of patients who are suitable candidates for therapy, establishing the goals of treatment (e.g., decreasing proteinuria, slowing disease progression, preventing ESRD), selecting an appropriate first-line therapy, and identifying suitable adjuvant treatments and salvage therapies.
Etiology and outcomes
The etiology of FSGS can have a major influence on therapeutic decision-making. The etiologic hallmark of primary idiopathic FSGS is podocyte injury while secondary types of FSGS (e.g., familial-genetic types, virus-associated FSGS, unilateral renal agenesis, and FSGS associated with renal dysplasia, surgical renal ablation, hypertension, and obesity) develop as a maladaptive response to glomerular “overwork.” The characteristic features of primary idiopathic FSGS include extensive foot process effacement, variable glomerulomegaly, and a clinical presentation consistent with full-blown nephrotic syndrome.
In contrast, secondary FSGS is characterized by limited foot process effacement, glomerulomegaly, and proteinuria without hypoalbuminemia. For example, obesity-related glomerulopathy (ORG) is an emerging epidemic (Kidney Int. 2001;59:1498-1509) and should be distinguished from idiopathic FSGS. Compared with patients with idiopathic FSGS, those with ORG are significantly older, more often Caucasian, and have lower incidences of nephrotic syndrome and nephrotic range proteinuria, higher serum albumin, and lower serum cholesterol levels. On renal biopsy, patients with ORG have more glomerulomegaly, fewer lesions of segmental sclerosis, and less extensive foot process effacement.
Corticosteroids and immunomodulatory agents are the mainstays of treatment in patients with primary idiopathic FSGS while ACE inhibitors and angiotensin receptor-blockers are more commonly used in patients with secondary FSGS.
The outcomes of patients with FSGS can be predicted by a variety of clinical and histologic variables. Favorable outcomes in patients with FSGS are associated with lower levels of proteinuria and serum crea-tinine and glomerular tip lesions on histologic examination. Unfavor-able outcomes may be predicted by African-American race, interstitial fibrosis, and collapsing FSGS histopathology. Remission of proteinuria, either complete or partial, is a strong predictor of increased survival rate in patients with FSGS (Kidney Int. 2004;66:1199-1205).