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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.)