BRB 8: Secondary FSGS

In this "Board Review Bonus" (BRB) episode, hosts Dr. Kenar Jhaveri and Dr. Koyal Jain break down the essential "must-knows" for Secondary Focal Segmental Glomerulosclerosis (FSGS). Geared toward board preparation and clinical practice, this bite-sized session covers everything from distinguishing secondary lesions from primary disease to navigating the modern cardiorenal toolkit.

Key Discussion Points

• Primary vs. Secondary Differentiation: Primary FSGS typically presents with full-blown nephrotic syndrome (heavy proteinuria, hypoalbuminemia, edema) and diffuse foot process effacement (>80%). Secondary FSGS usually manifests with indolent nephrotic-range proteinuria, normal serum albumin, and focal or mild foot process effacement.
• Decoding Biopsy Variants & Pathology: While Columbia classification variants (perihilar, tip, cellular, collapsing, NOS) are not strictly diagnostic on their own, specific patterns offer critical clues:
  • Perihilar & Glomerulomegaly: Point toward maladaptive, high-flow hyperfiltration states.
  • Collapsing Variant: Prompts a rigorous search for viral triggers (HIV, COVID-19) or drug-induced etiologies driven by high local interferon activity.
  • The "Global" Trap: Always distinguish true FSGS from secondary focal global glomerular sclerosis, which represents end-stage scarring rather than a primary podocytopathy.
• Pathogenesis: A mismatch between nephron mass and body mass causes glomerular hypertrophy, compensatory hyperfiltration, and increased intraglomerular pressure, leading to podocyte dropout and cytoskeletal damage.
• Comprehensive Causes: Spanning familial/genetic risk variants (APOL1), adaptive responses (reduced nephron mass, obesity, hypertension), viral triggers, and drug-induced injuries (lithium, CNIs, bisphosphonates).
• Management & The GDMT Era: Treatment focuses on reducing glomerular workload rather than immune suppression. Essential pillars include maximum RAAS blockade, SGLT2 inhibitors, GLP-1 receptor agonists, and sparsentan (backed by DUPLEX trial data for proteinuria reduction).

Recommended Literature & Resources:

• De Vriese AS, et al. Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach. J Am Soc Nephrol. 2018 Mar;29(3):759-774. PMID: 29321142
• Rheault MN, et al. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. N Engl J Med. 2023 Dec 28;389(26):2436-2445. PMID: 37921461
• Concept Map: Focal Segmental  Glomerulosclerosis(FSGS): http://www.nephronpower.com/2011/12/concept-map-focal-segmental.html