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

GLOMERULAR DISEASE DIAGNOSIS

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 https://www.ncbi.nlm.nih.gov/pubmed/28242845D’Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med. 2011 https://www.ncbi.nlm.nih.gov/pubmed/22187987 Fogo AB. Causes and pathogenesis of focal segmental glomerulosclerosis. Nat Rev Nephrol. 2015 https://www.ncbi.nlm.nih.gov/pubmed/25447132

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