Kidney nontumor / medical renal

Glomerular disease

Minimal change disease

Minimal change glomerulopathy


Editor-in-Chief: Debra L. Zynger, M.D.
Ana Belén Larqué, M.D., Ph.D.

Last author update: 17 August 2023
Last staff update: 17 August 2023

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PubMed Search: Minimal change glomerulopathy

Ana Belén Larqué, M.D., Ph.D.
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Cite this page: Larqué AB. Minimal change glomerulopathy. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneyminchange.html. Accessed April 14th, 2024.
Definition / general
  • Idiopathic glomerular disease that causes nephrotic syndrome
  • Little or no light or immunofluorescent microscopic abnormalities
  • Diffuse podocyte foot process effacement on electron microscopy (BMC Nephrol 2018;19:207)
Essential features
  • Renal glomeruli appear normal by light and immunofluorescence microscopy
  • Extensive effacement of podocyte foot processes by electron microscopy (hallmark)
  • Highly selective proteinuria, mainly albuminuria
  • Responds well to treatment with corticosteroids (90 - 95%)
Terminology
  • Also called minimal change disease, idiopathic nephrotic syndrome, nil disease, lipoid nephrosis and foot process disease
ICD coding
  • ICD-10: N00 - N08 - glomerular diseases
  • ICD-10: N04.9 - nephrotic syndrome with unspecified morphologic changes
Epidemiology
  • Most common type of nephrotic syndrome in children: 70 - 90%; in adults: 11 - 16%
  • Peak incidence in children: 2 - 3 years; in adults: 80 - 91 years
  • In children, M:F = 2:1; in adults, M = F
  • More common in white than in black and Asian patients (Clin J Am Soc Nephrol 2007;2:445)
Sites
  • Glomerular disease
Pathophysiology
Etiology
Diagrams / tables

Images hosted on other servers:
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Lipoid nephrosis

Clinical features
  • Nephrotic syndrome
  • Proteinuria selective for albumin, causing hypoalbuminemia leading to severe edema
  • Lipiduria, hypercholesterolemia but usually no hypertension, no hematuria and no azotemia
  • Microhematuria (10 - 30%)
  • Can present as acute renal insufficiency in adults (Clin J Am Soc Nephrol 2017;12:332)
  • Can present with IgA nephropathy (Clin J Am Soc Nephrol 2014;9:1033)
Diagnosis
  • Nephrotic syndrome with little or no light or immunofluorescent microscopic abnormalities
  • Diffuse foot process effacement on electron microscopy
Laboratory
Prognostic factors
  • Rarely, if ever, leads to end stage renal disease without development of focal segmental glomerulosclerosis
  • Adults with minimal change disease and acute renal failure also usually fully recover (Medicine (Baltimore) 2014;93:e300)
  • Relapses common and often lead to steroid dependence
Case reports
Treatment
Gross description
  • Enlarged, waxy, yellow cortex due to lipid accumulation in proximal tubules
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Ana Belén Larqué, M.D., Ph.D.
Normal glomerulus

Normal glomerulus

Normal glomerulus and interstitium

Normal glomerulus and interstitium

Tubules with hyaline droplets

Tubules with hyaline droplets

Aggregates of lipid laden macrophages

Immunofluorescence description
  • Negative except for variable focal IgM with or without C3
  • Punctate IgG podocyte staining in a subset of cases associated with antinephrin antibodies (J Am Soc Nephrol 2022;33:238)
Electron microscopy description
  • Extensive foot process effacement (foot processes retract into cell bodies, not actually fusion) (Nephrology (Carlton) 2014;19:392)
  • Microvillous transformation of epithelial cells, cyst formation
Electron microscopy images

Contributed by Ana Belén Larqué, M.D., Ph.D. and Nicole K. Andeen, M.D.
Foot process effacement

Foot process effacement

Hypertrophic podocytes

diffuse podocyte foot process effacement diffuse podocyte foot process effacement

Diffuse podocyte foot process effacement



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Foot process effacement

Genetics
  • Rarely familial (Semin Nephrol 2003;23:141, Hum Mol Genet 1995;4:2155, J Am Soc Nephrol 2002;13:388)
    • Histologic findings of focal segmental glomerulosclerosis or more rarely minimal change glomerulopathy are a part of the autosomal recessive steroid resistant nephrotic syndrome
    • Mutations in NPHS2 have been detected in both familial and sporadic steroid resistant nephrotic syndrome
    • NPHS2 gene, formerly SRN1, encodes podocin, a protein that is almost exclusively expressed in glomerular podocytes
  • More than 24 genes are currently known to be pathogenic in steroid resistant nephrotic syndrome (Clin J Am Soc Nephrol 2013;8:637)
Sample pathology report
  • Left kidney, biopsy:
    • Minimal change glomerulopathy
    • Adequacy: adequate (cortex 85%, medulla 15%)
    • Microscopic description: 19 glomeruli showed normal size and cellularity. There is no interstitial inflammation and no significant interstitial fibrosis or tubular atrophy. Tubules are preserved, without significant evidence of injury. Small arteries and arterioles show minimal interstitial fibrosis. There is no vasculitis.
    • Immunofluorescence microscopy:
      • Number of glomeruli: 4
      • There were no deposits of IgA, IgM, IgG, C3, C1q or fibrin
    • Electron microscopy: Extensive effacement of the foot processes covering over 80% of the glomerular capillary surface. The glomerular basement membrane showed normal thickness and a generally smooth contour. No electron dense deposits were noted on the glomerular capillary basement membranes or mesangial areas. The mesangial area contained normal amounts of matrix and cells.
Differential diagnosis
  • Focal segmental glomerulosclerosis:
    • Segmental hyalinosis or synechiae to Bowman capsule, interstitial fibrosis or tubular atrophy
    • Cases with unsampled glomerulosclerosis may be misdiagnosed as minimal change disease
  • Secondary causes of minimal change disease (Nephrol Dial Transplant 2003;18:vi52):
    • Secondary to drugs, especially nonsteroidal anti-inflammatory drugs
    • Features of acute interstitial nephritis support the diagnosis
    • May precede or occur simultaneously with the diagnosis of Hodgkin disease or other diseases (hematologic malignancies, thymoma, food allergies, infectious, etc.)
  • Genetic disease (Front Med (Lausanne) 2021;8:761600):
    • Should be considered in patients with family history of nephrotic syndrome, disease onset within the first 6 months of life or steroid resistant nephrotic syndrome
  • Mesangial glomerulonephritis:
    • Early mesangial glomerulonephritis can be indistinguishable on light microscopy
    • Positive immunofluorescence and electron dense subepithelial deposits on electron microscopy
  • Chyluria:
    • Normal podocytes with heavy proteinuria
  • IgA nephropathy:
    • Minimal change disease could be superimposed on IgA nephropathy
  • IgM nephropathy:
    • Possibly a variant of minimal change disease / focal segmental glomerulosclerosis
    • Diffuse, global mesangial staining for IgM (≥ 2+) in cases that otherwise resemble minimal change disease; codeposits of C3 in 30+%
  • C1q nephropathy:
    • Dominant or codominant mesangial staining for C1q (≥ 2+) by immunofluorescence; other deposits are C3, IgG and IgM
    • Light microscopic findings range from normal appearing glomeruli to mesangial proliferation to focal or diffuse endocapillary proliferation and frequently reveal focal segmental glomerulosclerosis
Board review style question #1
Which of the following is true about minimal change glomerulopathy?

  1. Interstitial inflammation and fibrosis are usually absent
  2. It is the most common type of nephrotic syndrome in adults
  3. Monoclonal antibody therapy should be the first line therapy
  4. Pretreatment biopsy is always done
Board review style answer #1
A. Interstitial inflammation and fibrosis are usually absent. Answer B is incorrect because membranous nephropathy is the most frequent cause of nephrotic syndrome in adults. Answer C is incorrect because corticosteroids are the first line therapy. Answer D is incorrect because in the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses.

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Reference: Minimal change glomerulopathy
Board review style question #2
Which of the following signs and symptoms is common in minimal change disease?

  1. Azotemia
  2. Hypertension
  3. Macrohematuria
  4. Selective proteinuria
Board review style answer #2
D. Selective proteinuria. Minimal change disease usually presents with proteinuria selective for albumin, causing hypoalbuminemia leading to severe edema. Answers A - C are incorrect because minimal change disease is associated with lipiduria and hypercholesterolemia but usually no hypertension, no hematuria and no azotemia.

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Reference: Minimal change glomerulopathy
Board review style question #3

Which of the following renal lesions is most likely to be present in minimal change disease?

  1. Acute tubular necrosis
  2. Glomerular crescent formation
  3. Mesangial immune complex deposition
  4. Podocyte foot process effacement
Board review style answer #3
D. Podocyte foot process effacement. Minimal change disease is an idiopathic glomerular disease that causes nephrotic syndrome with little or no immunofluorescent microscopic abnormalities. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy.

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Reference: Minimal change glomerulopathy
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