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Obesity Related Glomerulopathy

Updated: Jun 7, 2023


NEPHROPATHOLOGY






















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.




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.)




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