Obesity-related Glomerulopathy

By Jonathan E. Zuckerman, M.D. Ph.D.
HS Assistant Clinical Professor
Service Chief, Renal Pathology
Director, Surgical Pathology Fellowship
UCLA Department of Pathology and Laboratory Medicine

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.


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.)

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