Minimal change glomerulopathy

Kidney nontumor
Primary glomerular diseases
Minimal change glomerulopathy

Author: Ana Belén Larqué, M.D., Ph.D.

Editor-in-Chief: Debra Zynger, M.D.

Topic Completed: 8 January 2019

Revised: 6 February 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: Minimal change glomerulopathy[TIAB]

Page views in 2019: 4,017

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Table of Contents

Cite this page: Larqué AB. Minimal change glomerulopathy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyminchange.html. Accessed March 29th, 2020.

Definition / general

Idiopathic glomerular disease that causes nephrotic syndrome
Little or no light or immunofluorescent microscopic abnormalities
Diffuse 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 Caucasians and Asians than African Americans (Clin J Am Soc Nephrol 2007;2:445)

Sites

Glomerular disease

Pathophysiology

Extensive foot process "fusion" appears to be due to epithelial injury with loss of glomerular anionic charge (Kidney Int 1984;25:696)
Unknown circulating factor that triggers podocyte dysfunction postulated (Pediatr Nephrol 2018;33:1101)
Minimal change disease, diffuse mesangial hypercellularity and focal segmental glomerulosclerosis may be a continuum of the same disease (Kidney Int 2004;65:1690)

Etiology

Usually idiopathic, especially in children (Clin J Am Soc Nephrol 2017;12:332)
Secondary forms due to virus, drugs, allergic reactions, immunologic diseases and neoplasia at all ages (BMC Nephrol 2018;19:162, Intern Med 2014;53:1131, Case Rep Nephrol 2015;2015:987212, J Surg Oncol 2010;102:704)
Rarely familial (gene mutations: NPHS2, dysferlin) (Semin Nephrol 2003;23:141)

Diagrams / tables

Images hosted on other servers:

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)

Diagnosis

Nephrotic syndrome with little or no light or immunofluorescent microscopic abnormalities
Diffuse foot process effacement on electron microscopy

Laboratory

CD80 in urine may be a marker (Pediatr Nephrol 2015;30:309)

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

2 and 15 year old boys with steroid responsive nephrotic syndrome complicated by cerebral venous sinus thrombosis (Nefrologia 2015;35:497)
29 year old woman with type I neurofibromatosis and complete remission after neurofibroma resection (Korean J Intern Med 2017;32:186)
33 year old man with severe chronic sinusitis (Intern Med 2015;54:2373)
50 year old woman with minimal change disease after a type B influenza infection (BMC Nephrol 2018;19:162)
68 year old man with marginal zone MALT lymphoma manifesting as nephrotic range proteinuria (Clin Nephrol 2016;85:184)

Treatment

Corticosteroids
Immunosuppressive agents in steroid resistant cases (cyclophosphamide, rituximab, abatacept) (Kidney Int 2013;83:511, Pediatr Nephrol 2015;30:469)

Gross description

Enlarged, waxy yellow cortex due to lipid accumulation in proximal tubules

Microscopic (histologic) description

Glomerulus normal by light microscopy except for variable podocyte hypertrophy
Protein reabsorption droplets in tubules (Zhou: Silva's Diagnostic Renal Pathology, 2nd Edition, 2017)

Microscopic (histologic) images

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

Aggregates of lipid laden macrophages

Images hosted on other servers:

Relatively normal
appearing glomeruli
and lipoid nephrosis

Immunofluorescence description

Negative except for variable focal IgM ± C3

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

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

Hypertrophic podocytes

Images hosted on other servers:

Foot process effacement

Molecular / cytogenetics description

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

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
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

Additional references

Colvin: Diagnostic Pathology - Kidney Diseases, 2nd Edition, 2015

Board review style question #1

Which of the following is true about minimal change glomerulopathy?

Interstitial inflammation and fibrosis are usually absent
It is the most common type of nephrotic syndrome in adults
Monoclonal antibody therapy should be the first line therapy
Pretreatment biopsy is always done

Board review answer #1

A. Interstitial inflammation and fibrosis are usually absent

Comment Here

Reference: Minimal change glomerulopathy

Board review style question #2

Which of the following signs and symptoms is common in minimal change disease?

Azotemia
Hypertension
Macrohematuria
Selective proteinuria

Board review answer #2

D. Selective proteinuria

Comment Here

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?

Acute tubular necrosis
Glomerular crescent formation
Mesangial immune complex deposition
Podocyte foot process effacement

Board review answer #3

D. Podocyte foot process effacement

Comment Here

Reference: Minimal change glomerulopathy