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FSGS: A Clinicopathological Correlation and Case-Based Approach Toward the Correct Diagnosis

Updated: Jun 7, 2023


FSGS: A Clinicopathological Correlation and Case-Based Approach Toward the Correct Diagnosis

In this session of Nephropathology Essentials, Dr. Rennke presented a case-based approach to FSGS. Our Moderator’s Notes are derived from his live presentation

By Dr. Pravir Baxi

Key points:

  • Podocyte (visceral epithelial cell) injury is the hallmark of proteinuria

    • Diffuse podocytopathy typically manifests as nephrotic syndrome with edema, hypoalbuminemia, and nephrotic range proteinuria

    • Focal podocytopathy typically results in modest amount of proteinuria without overt nephrotic syndrome features

    • Important to further differentiate from acquired and genetic causes

  • Dr. Rennke shared his approach to the differential diagnosis of FSGS pattern of injury:

    • Idiopathic or Primary FSGS

      • Etiology –“Permeability Factor”

      • Sudden onset of nephrotic syndrome

      • Pathological Characteristics

        • Normal-sized glomeruli, diffuse effacement of foot process, no significant chronicity

    • Familial and Genetic FSGS

      • Genetic Podocytopathies with focal Injury

        • Include ACTN4 (alpha-actinin-4), TRPC6 (canonical transient receptor potential 6), INF2 (formin family of actin-regulating proteins), APOL1 mutations

      • Genetic Podocytopathies with Diffuse Injury

        • Include NPHS2 (podocin), NPHS1 (nephrin), PLC31 (phospholipase C epsilon), WT1 (Wilms tumor gene) mutations

    • Secondary or Adaptive FSGS

      • The initial loss of functioning nephrons followed by adaptations

        • Examples: Unilateral renal agenesis, segmental hypoplasia, and oligomeganephronie, reflux nephropathy, primary glomerulopathies, partial cortical necrosis, sickle cell disease, atheroembolic disease, cystic disease

      • Without an initial loss of nephrons but with functional maladaptation

        • Diabetic Nephropathy, Obesity-associated, Glycogen storage disease

      • Slowly progressive proteinuria without edema, typically hx of prior kidney disease

      • Pathological Features

        • Glomerular hypertrophy

        • Focal foot process effacement (primarily preserved)

    • Segmental Glomerular Scarring

Selected References:

Rosenberg AZ, Kopp JB. Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol. 2017’Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med. 2011 Fogo AB. Causes and pathogenesis of focal segmental glomerulosclerosis. Nat Rev Nephrol. 2015


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