Kidney nontumor
Glomerular disease
Obesity related glomerulopathy
Obesity related glomerulopathy


Minor changes: 12 October 2020

Copyright: 2020, PathologyOutlines.com, Inc.

PubMed Search: Obesity related glomerulopathy "free full text"[SB]

Alireza Samiei, M.D.
Jonathan E. Zuckerman, M.D., Ph.D.
Page views in 2020 to date: 64
Cite this page: Samiei A, Zuckerman JE. Obesity related glomerulopathy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyobesity.html. Accessed October 21st, 2020.
Definition / general
  • Glomerulomegaly with or without accompanying focal segmental glomerulosclerosis occurring in the setting of obesity with or without the metabolic syndrome
Essential features
  • Glomerulomegaly is the pathological hallmark (Kidney Int 2001;59:1498)
  • Hypertrophied glomeruli that fill the microscopic visual field at 40x objective lens
  • Often secondary / maladaptive focal segmental glomerulosclerosis present (Nephron 2017;136:273)
  • Segmental patchy podocyte foot process effacement (Nephron 2017;136:273)
  • Proteinuric presentation, most often subnephrotic
Terminology
  • Obesity related glomerulopathy
  • Metabolic syndrome related glomerulopathy
ICD coding
  • ICD-10: N08 - glomerular disorders in diseases classified elsewhere
Epidemiology
Sites
  • Kidney
Pathophysiology
  • Congenital or functional low nephron endowment (Kidney Int 2000;58:770)
  • Glomerular filtration rate (GFR) is increased in order to maintain adequate natriuresis in obesity
  • Leads to adaptive hemodynamic modulations and glomerular hypertension
  • Chronic glomerular hypertension causes nephron injury, which manifests as glomerular hypertrophy, basement membrane thickening and podocyte damage
  • Subsequent podocyte loss from continued mechanical injury eventually leads to podocyte loss and segmental sclerosis (Kidney Int 1992;42:148, Am J Hypertens 1988;1:335)
  • May also be contributions from endocrinopathies of metabolic syndrome
  • Obstructive sleep apnea may also be a contributing factor
Etiology
Clinical features
  • Middle aged adults (35 - 45 years) (Am J Kidney Dis 2008;52:58)
  • Slowly progressive proteinuria (Kidney Int 2001;59:1498)
  • Proteinuria often subnephrotic but may reach nephrotic range
  • Nephrotic syndrome is rare
  • Slow decline in renal function
  • Sometimes present without overt clinical disease
Diagnosis
  • Diagnosis is made on renal biopsy (Kidney Int 2008;73:947)
  • Can be suspected clinically in obese patients with proteinuria
Laboratory
  • Patients commonly present with proteinuria, sometimes in nephrotic range
  • Median estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m² (Kidney Int 2019;95:647)
Prognostic factors
  • Body mass index (BMI) is directly proportional to risk of end stage renal disease
Case reports
  • 37 year old Caucasian man with a BMI of 38 kg/m² presented to general nephrology clinic with a 3+ proteinuria on urinalysis (Oxf Med Case Reports 2020;2020:omz148)
  • 49 year old morbidly obese Caucasian man was found to have obstructive sleep apnea, proteinuria and renal insufficiency (Am J Kidney Dis 1987;10:470)
  • 69 year old Caucasian man, with previous normal renal function, suffering from diabetes mellitus, obesity (BMI = 38 kg/m²), hypercholesterolemia, hypertension and coronary artery disease started hemodialysis because of severe acute renal failure (Bioimpacts 2015;5:155)
Treatment
  • Weight loss
  • Renin angiotensin system blockade
  • Bariatric surgery
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Jonathan E. Zuckerman, M.D., Ph.D.
Glomerulomegaly

Glomerulomegaly

Perihilar FSGS

Perihilar focal segmental glomerulosclerosis

Glomerulomegaly

Glomerulomegaly

Glomerulomegaly, tubular hypertrophy

Glomerulomegaly, tubular hypertrophy

Perihilar FSGS

Perihilar focal segmental glomerulosclerosis

Normal glomerulus

Immunofluorescence description
  • Glomeruli negative for immune complex deposits
  • Nonspecific accumulation of IgM and complement C3 in sclerotic and hyalinized lesion (Kidney Int 2001;59:1498)
  • Podocytes may contain intracytoplasmic protein resorption droplets that stain for IgG, IgA and albumin
Immunofluorescence images

Contributed by Jonathan E. Zuckerman, M.D., Ph.D.
FSGS

Focal segmental glomerulosclerosis

Electron microscopy description
  • Podocytes exhibit segmental foot process effacement (25 - 40%)
  • Mild thickening of glomerular basement membrane
  • Mild mesangial sclerosis
  • Podocytes and mesangial cells will contain lipid droplets (Lancet Diabetes Endocrinol 2014;2:417)
  • Lipid vacuoles can be seen in the tubular epithelial cells of the proximal tubule
  • No immune complex deposits
Electron microscopy images

Contributed by Jonathan E. Zuckerman, M.D., Ph.D.
Mild GBM thickening

Mild GBM thickening

Segmental foot process effacement

Segmental foot process effacement

Genetics
  • Unknown at this time
Sample pathology report
  • Left kidney, native, needle core biopsy:
    • Glomerulomegaly with secondary focal segmental glomerulosclerosis (FSGS), perihilar variant consistent with obesity related glomerulopathy (see comment)
    • Comment: In addition to obesity, other clinical risk factors for these biopsy findings may include obstructive sleep apnea, chronic hypertension and diabetes. These findings may also reflect situations of congenital or acquired states of low nephron number (e.g. low birth weight) or congenital susceptibility to maladaptive glomerular injury.
Differential diagnosis
Board review style question #1

A morbidly obese patient has a renal biopsy for subnephrotic range proteinuria that has been gradually worsening. Her serologic workup is negative. A renal biopsy is performed and is significant for the histologic finding shown above. Immunofluorescence is negative and there are no electron dense deposits or glomerular basement membrane abnormalities by light microscopy. What is the most likely diagnosis?

  1. IgA nephropathy
  2. Lupus nephritis
  3. Minimal change disease
  4. Obesity related glomerulopathy
Board review answer #1
D. Obesity related glomerulopathy

Comment Here

Reference: Obesity related glomerulopathy
Board review style question #2

A 50 year old Caucasian woman is found to have mild proteinuria during routine urinary screening. Her serologic workup is negative. A renal biopsy is performed and is significant for the finding shown above. Immunofluorescence is negative and there are no electron dense deposits or glomerular basement membrane abnormalities by light microscopy. In which clinical settings is this biopsy finding typically seen?

  1. Advanced diabetic disease
  2. Elevated BMI
  3. Lupus
  4. Mild essential hypertension
Board review answer #2
B. Elevated BMI

Comment Here

Reference: Obesity related glomerulopathy
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