Table of Contents
Definition / general | Pathophysiology | Diagrams / tables | Clinical features | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Immunofluorescence | Immunofluorescence images | Electron microscopy description | Electron microscopy images | Differential diagnosisCite this page: Sangle, N. Minimal change glomerulopathy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyminchange.html. Accessed April 22nd, 2018.
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
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
- Intravascular B cell lymphoma of kidney associated with minimal change disease (Hum Pathol 1989;20:263)
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
Immunofluorescence
- Generally negative
- May show weak nonspecific IgM in mesangial distribution, but no deposits in GBM
- Albumin in proximal tubular epithelial cells
Immunofluorescence images
Electron microscopy description
- Extensive foot process effacement (foot processes retract into cell bodies, not actually fusion)
- Microvillous transformation of epithelial cells, cyst formation
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