A representative clinical presentation:

The patient is a 45 year old man with worsening proteinuria that is now ~2g. His past medical history is significant for long-standing hypertension, pre-diabetes, obstructive sleep apnea, and obesity (BMI 36). Serologic workup including ANA, ANCA, SPEP/UPEP, RF, cryocrit, HIV, and hepatitis serologies are negative. His complement levels are normal. His serum creatinine is mildly elevated. A renal biopsy was performed and was significant for the following findings.

Diagnosis:

Obesity-related glomerulopathy

Key points:

• • Defined as glomerulomegaly (glomerular hypertrophy) with or without secondary adaptive segmental glomerulosclerosis arising in obese patients with body mass index >30 kg/m2
  • Obesity-associated glomerular hyperfiltration results in prolonged podocyte shear stress with loss of adhesions and detachment ultimately with segmental sclerosis formation
  • Similar findings reported in “moderate obesity” (BMI 25-30) suggest some degree of an undetermined genetic component
  • Generally presents as slowly progressive proteinuria that may eventually reach nephrotic range but not a true nephrotic syndrome
  • Histologic features
    • Enlarged glomeruli (>1/2 of a 40x high powered field)
    • Thickened GBM
    • May see increased mesangial matrix
    • Segmental sclerosis, most often a perihilar variant
    • Tubular cross-sections enlarged
    • Often less interstitial fibrosis/tubular atrophy than other cause of maladaptive glomerular injury
    • IF studies are negative (non-specific IgM, C3, and C1q staining of segments of sclerosis may be present)
    • EM with patchy partial podocyte foot process effacement (usually ranges from 25-40%)
  • Differential diagnoses
    • Diabetic nephropathy may show overlapping features and may be indistinguishable. May show hyalinization of both afferent and efferent arterioles
    • Primary FSGS will show more extensive podocyte foot process effacement (>75%) and present as true nephrotic syndrome
    • Other causes of maladaptive glomerular injury (e.g, renal hypoplasia, obstructive nephropathy, arterionephrosclerosis, etc.)