Kidney nontumor
Primary glomerular diseases
Minimal change glomerulopathy

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 30 October 2017, last major update March 2014

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Minimal change glomerulopathy [title]
Cite this page: Sangle, N. Minimal change glomerulopathy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyminchange.html. Accessed December 14th, 2017.
Definition / general
  • Also called minimal change disease, nil disease, lipoid nephrosis and foot process disease
  • Causes 80% of cases of nephrotic syndrome in children (usually ages 2 - 6), 20% in adults
Pathophysiology
  • Extensive foot process "fusion" appears to be due to epithelial injury with loss of glomerular anionic charge
  • Overproduction of angiopoietin-like 4 (ANGPTL4) in podocytes causes it to bind to glomerular basement membrane, leading to selective proteinuria, diffuse effacement of foot processes and loss of glomerular basement membrane charge (Am J Kidney Dis 2012;59:284, Nat Med 2011;17:117); due in part to sialic acid residue deficency in ANGPTL4 (oral supplementation with sialic acid precursor N-acetyl-d-mannosamine improves sialylation of podocyte-secreted ANGPTL4 and significantly decreases proteinuria)
  • "Fusion" is actually simplification of epithelial architecture with flattening, retraction and swelling of foot processes; also seen in membranous glomerulopathy and diabetes; reverts to normal with remission
Diagrams / tables

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Lipoid nephrosis

Clinical features
  • Nephrotic syndrome, proteinuria selective for albumin, causing hypoalbuminemia leading to severe edema
  • Elevated serum cholesterol, but with minimal microscopic glomerular alterations and usually no hypertension, no hematuria and no azotemia
  • Note: minimal change disease, diffuse mesangial hypercellularity and focal and segmental glomerulosclerosis may be a continuum of the same disease
  • Associated with respiratory infections, immunizations, lead or mercury ingestion, allergies, acute interstitial nephritis and Hodgkin’s lymphoma; in elderly, associated with NSAIDs
Case reports
Treatment
  • 90% of children respond to steroids initially (foot processes return to normal), may require immunosuppression, < 5% develop renal failure after 25 years
  • Some children become steroid dependent / resistant, but this usually resolves at puberty
  • Older adults with hypertension and severe proteinuria have a higher risk of reversible renal failure
  • Rituximab may be effective in adults (Clin Nephrol 2011;76:151)
  • May develop nephrocalcinosis due to hypercalciuria from chronic furosemide use (Hum Pathol 2000;31:1363)
Microscopic (histologic) description
  • Normal glomeruli, tubules have lipid droplets due to reabsorption of lipoproteins that leak from glomeruli ("lipoid nephrosis")
Microscopic (histologic) images

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Relatively normal appearing glomeruli and lipoid nephrosis

Immunofluorescence
  • Generally negative
  • May show weak nonspecific IgM in mesangial distribution, but no deposits in GBM
  • Albumin in proximal tubular epithelial cells
Immunofluorescence images

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Only background staining by immunofluorescence

Electron microscopy description
  • Extensive foot process effacement (foot processes retract into cell bodies, not actually fusion)
  • Microvillous transformation of epithelial cells, cyst formation
Electron microscopy images

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Foot process effacement

Differential diagnosis
  • Focal and segmental glomerulosclerosis: tubular atrophy and interstitial scarring; global glomerular sclerosis may be present in minimal change disease if there is underlying arterionephrosclerosis; minimal change disease may also be associated / superimposed on other conditions such as IgA nephropathy