Focal Segmental Glomerulosclerosis Differential Diagnoses

Updated: Oct 03, 2022
  • Author: Sreepada TK Rao, MD, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Diagnostic Considerations

In patients presenting with nephrotic syndrome, distinguishing focal segmental glomerulosclerosis (FSGS) from other glomerular diseases (eg, minimal-change disease, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis, membranous glomerulonephritis) is clinically difficult. Age and race may help guide diagnostic considerations:

  • In young Black men, FSGS is the commonest cause of nephrotic syndrome.
  • In young women, nephrotic syndrome may rarely be the initial manifestation of systemic lupus erythematosus (SLE). [27]
  • In young patients, amyloidosis of the kidneys (except in rare familial forms) is very uncommon as a cause of nephrotic syndrome.
  • Although hematuria is the most common presentation in Whites with IgA nephropathy, nephrotic syndrome and renal insufficiency may also be present.

Serologic studies such as complement C3 and antinuclear antibody (ANA) are helpful to exclude SLE.  In patients with FSGS, red blood cell casts are usually not present on urinalysis. 

Zhang et al reported that the urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and retinol-binding protein (RBP) may be useful biomarkers for FSGS. In their study, levels of urinary NGAL, NAG, and RBP were higher in patients with FSGS (n=32) than in patients with minimal change nephrotic syndrome with comparable proteinuria (n=22). A cutoff value of 15.87ng/mL NGAL demonstrated 87.1% sensitivity and 59.1% specificity for the diagnosis of FSGS. Response to immunosuppressive therapy was significantly different in patients with KIM-1, NAG, and RBP levels below and above the cutoff values. [40]

Other causes of nephrotic syndrome in adults include the following:

  • Minimal change disease
  • Membranous glomerulonephritis
  • IgA nephropathy
  • Diabetes mellitus
  • Amyloidosis