Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) can be considered a set of six syndromes, including primary FSGS, adaptive FSGS, APOL1 FSGS, high-penetrance genetic FSGS, virus-associated FSGS, and medication-associated FSGS. These distinctions based on pathogenetic mechanism have therapeutic and prognostic value. In the latter four syndromes, the diagnosis is generally based upon clear-cut criteria. The distinction between primary FSGS and adaptive FSGS is more difficult for the clinician, as it involves assessing historical, laboratory, and kidney pathology data and integrating these data without an evidence-based approach to make the distinction. Nevertheless, the distinction between primary FSGS and adaptive FSGS drives the clinician's decision to choose between starting immunosuppressive therapy on the one hand and pursuing a more conservative course on the other hand, including renin-angiotensin system inhibitors, thiazide diuretics, and dietary sodium restriction. APOL1 FSGS may present with features typical of either primary FSGS or adaptive FSGS and at present is probably best treated in the ways in which those syndromes are treated. Specific forms of genetic FSGS may respond to glucocorticoids or coenzyme Q10 supplementation, suggesting that genetic testing should be pursued in particular clinical settings. Virus-associated FSGS and medication FSGS are addressed by removing the responsive agent, when possible. With regard to primary FSGS and APOL1 FSGS, current therapies are often ineffective, and therapies that address molecular mechanisms are very much needed.