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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