Overview of The Pathogenesis and Causes of Glomerulonephritis in Children

Overview of the pathogenesis and causes of glomerulonephritis in children - UpToDate 08/12/17 06.
37
Official reprint from UpToDate

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Overview of the pathogenesis and causes of glomerulonephritis in children
Author: Patrick Niaudet, MD

Section Editor: F Bruder Stapleton, MD
Deputy Editor: Melanie S Kim, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2017. | This topic last updated: Nov 18, 2016.
INTRODUCTION Glomerulonephritis (GN) generally presents as a constellation of findings that include

hematuria, proteinuria, edema, and often hypertension. GN is caused by a number of disorders that are all
characterized by glomerular injury accompanied by inflammation. In some cases, GN may progress to renal
failure.
The pathogenesis and etiology of glomerulonephritis in children will be reviewed here. The approach to
evaluating a child with glomerulonephritis is discussed separately. (See "Evaluation of a child with glomerular
disease".)
PATHOGENESIS Although the pathogenesis is not fully understood, current evidence suggests that most
cases of glomerulonephritis (GN) are due to an immunologic response to a variety of different etiologic
agents. The immunologic response, in turn, activates a number of biological processes (eg, complement
activation, leukocyte recruitment, and release of growth factors and cytokines) that result in glomerular
inflammation and injury [1,2]. GN may be isolated to the kidney (primary glomerulonephritis) or be a
component of a systemic disorder (secondary glomerulonephritis) (table 1).
The immunologic mechanisms involved in the pathogenesis of GN are briefly reviewed here and are
discussed in greater detail separately. (See "Mechanisms of immune injury of the glomerulus".)
Immunologic damage Humoral (also referred to T helper cell 2-regulated) immune response to a variety
of inciting agents results in immunoglobulin deposition and complement activation within the glomeruli. In
most of these disorders, immune complex deposition is an active process caused by in situ binding of
antibodies to antigens localized within the glomeruli. The antigens may be structural glomeruli components,
such as the Goodpasture antigen in the non-collagenous domain of the alpha-3 chain of type IV collagen in
the glomerular basement membrane (GBM) [3].
Alternatively, the antigens may be trapped or deposited within the glomerulus, including self-antigens such as
DNA in the form of nucleosomes in lupus nephritis, or exogenous antigens due to infectious agents such as
bacteria (Streptococcus, Staphylococcus), viruses (hepatitis B), or tumor antigens. These in situ-formed
immune complexes may enlarge if there is further immune response consisting of polyclonal B-cell activation,
which induces the formation of different antibodies. These include rheumatic factors immunoglobulin M (IgM),
anti-immunoglobulin G (IgG), or anti-idiotypic antibodies that bind to these complexes.
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Overview of the pathogenesis and causes of glomerulonephritis in children - UpToDate 08/12/17 06.37
Another possible mechanism for immune complex deposition is the passive process of trapping circulating
immune complexes within the glomeruli. Although this process has been studied in animal models (serum
sickness disease), it appears to be less commonly seen in human GN than in situ glomerular immune
complex formation.
Glomerulonephritis that is due to antibody formation requires the presence of T lymphocytes. However, T
lymphocytes may also cause glomerulonephritis in the absence of antibodies, as demonstrated in an
experimental rat model [4]. Although the mechanism for this cellular-mediated immunity is less well-defined in
humans, it appears to involve activation of both T cell lymphocytes and macrophages, particularly in rapidly
progressive (crescentic) GN. (See "Mechanisms of glomerular crescent formation", section on 'Macrophages'
and "Mechanisms of glomerular crescent formation", section on 'T cells'.)
Secondary processes The primary immunologic pathologic process activates the following systems that
contribute to the inflammatory response and glomerular damage. (See "Mechanisms of immune injury of the
glomerulus", section on 'Inflammatory mechanisms of glomerular injury'.)
Complement system The humoral immunologic response activates the classic complement pathway
[5]. In some renal disorders (eg, membranoproliferative type II and poststreptococcal glomerulonephritis)
the alternative pathway is activated. Complement activation results in generation of chemotactic and
chemokinetic peptides (C3a, C5a, and C3b) that attract white cells to the site of injury, and formation of
the membrane attack complex (C5b-C9), which may cause direct injury to glomerular cells [6] and results
in the release of cytokines, reactive oxygen species, and prostaglandins, and cell apoptosis [7]. (See
"Overview and clinical assessment of the complement system", section on 'Introduction'.)
Coagulation system In patients with rapidly progressive GN, direct injury to the endothelial cells
activates the coagulation cascade. This results in thrombi formation and fibrin deposition that are
important components in the formation of crescents. (See "Mechanisms of glomerular crescent
formation", section on 'Initiating events' and "Mechanisms of glomerular crescent formation".)
Leukocyte recruitment A constant feature of GN is the glomerular infiltration of leukocytes (neutrophils,

monocytes, and macrophages), which are sequentially recruited to the glomeruli by the coordinated
release of chemoattractants (eg, C3a, C5a, and CXC chemokines). When activated, these cells generate
reactive oxygen species (ROS, such as hydrogen peroxide) and lysosomal enzymes (which damage
endothelial cells, the GBM, and the mesangium), and growth factors (which induce fibrin deposition, cell
proliferation, and crescent formation). As in patients with granulomatosis with polyangiitis (previously
referred to as Wegner's granulomatosis), who have renal involvement, pathogenesis is due to adherence
to renal endothelial cells and release proteases, ROS, and inflammatory cytokines resulting in glomerular
injury. (See "Role of cytokines in the immune system" and "Pathogenesis of granulomatosis with
polyangiitis and related vasculitides", section on 'Neutrophil activation and ANCA'.)
Glomerular cells Injury to the glomerular endothelial and mesangial cells result in cell proliferation,
adhesion molecule expression, and the production and release of vasoactive molecules (endothelin and
nitric oxide), cytokines, ROS, growth factors, and prostaglandins.
Growth factors and cytokines Many growth factors and cytokines (eg, interleukins) are produced by
glomerular cells and by inflammatory cells. These small peptides bind to specific cell surface receptors
and may either promote or prevent renal injury.
Growth factors such as platelet-derived growth factor (PDGF), transforming growth factor (TGF)-
beta, and vascular endothelial growth factor (VEGF) have important roles in glomerular injury
involving glomerular cell proliferation, extra-cellular matrix deposition, and sclerosis.
Interleukins (IL) are known to play an important role in the inflammatory response. IL-1, IL-8, and IL-
18 have a proinflammatory action in glomerulonephritis [8]. IL-1 induces mesangial cell proliferation
and promotes the synthesis of several substances. IL-8 is produced by mesangial cells and is a
chemoattractant for granulocytes.
ETIOLOGIC CLASSIFICATION Because the differential diagnosis for glomerulonephritis (GN) is broad,
using a classification schema is helpful to narrow the causes of childhood GN in a systematic manner. The
etiology of GN can be classified by the following methods:
Clinical presentation
Histopathology
The preferred etiologic approach is to use the clinical presentation schema because the histopathologic
method requires a biopsy sample.
Clinical presentation The different clinical presentations include:
Acute glomerulonephritis
Rapidly progressive glomerulonephritis
Recurrent macroscopic hematuria
Chronic glomerulonephritis
Each clinical presentation includes several different renal diseases. A presumptive clinical diagnosis is made
based upon the presentation, the presence of extra-renal findings, family history, and laboratory testing,
including urinalysis. Histologic confirmation is made by renal biopsy (figure 1). (See "Evaluation of a child with
glomerular disease".)
Acute GN Acute GN typically presents as the sudden onset of hematuria (either gross or microscopic)
with proteinuria, decreased glomerular filtration rate, and retention of sodium and water, which usually results
in an elevated blood pressure and edema.
In children, the most common cause of acute GN is poststreptococcal GN [9-11]. Acute nephritis also has
been associated with other infectious agents (table 2). Other causes of acute GN include secondary GN (eg,
immunoglobulin A vasculitis [IgAV; Henoch-Schnlein purpura (HSP)], nephritis associated with subacute
bacterial endocarditis, and shunt nephritis). (See "Poststreptococcal glomerulonephritis" and "IgA vasculitis
(Henoch-Schnlein purpura): Clinical manifestations and diagnosis", section on 'Renal disease' and "Renal
disease in the setting of infective endocarditis or an infected ventriculoatrial shunt", section on 'Clinical
features and renal biopsy findings'.)
In addition, several causes of chronic GN may present as acute nephritic syndrome and may be initially
indistinguishable clinically from acute disorders. These chronic conditions include primary GN (eg, IgA
nephropathy and membranoproliferative GN [MPGN]) and secondary GN (eg, lupus nephritis). (See "Clinical
presentation and diagnosis of IgA nephropathy" and "Clinical presentation, classification, and causes of
membranoproliferative glomerulonephritis" and "Diagnosis and classification of renal disease in systemic
lupus erythematosus".)
Rapidly progressive GN Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome

manifested by features of acute GN and by progressive loss of renal function over a comparatively short
period of time (days, weeks, or months). It is characterized morphologically by extensive crescent formation
(picture 1A-E).
RPGN occurs rarely in children. Causes of pediatric RPGN include:
Primary GN IgA nephropathy, MPGN, and anti-glomerular basement membrane (GBM) disease
Secondary GN Granulomatosis with polyangiitis, lupus nephritis, poststreptococcal GN, IgAV (HSP)
nephritis, and microscopic polyangiitis
Early diagnosis with renal biopsy and serologic testing, and early initiation of appropriate therapy are
essential to minimize the degree of irreversible renal injury. Empiric therapy may be started in patients with
severe disease, particularly if either renal biopsy or interpretation of the biopsy will be delayed. However,
despite aggressive treatment, approximately half of the affected children will develop end-stage renal disease
(ESRD).
The clinical manifestations, diagnosis, and treatment of RPGN are discussed separately. (See "Overview of
the classification and treatment of rapidly progressive (crescentic) glomerulonephritis".)
Recurrent macroscopic hematuria In children, common presentations of IgA nephropathy are

transient episodes of macroscopic hematuria. These often occur one or two days after an upper respiratory
infection. Recurrent macroscopic hematuria may also be seen in children with Alport syndrome. (See "Clinical
presentation and diagnosis of IgA nephropathy", section on 'Clinical features' and "Clinical manifestations,
diagnosis, and treatment of Alport syndrome (hereditary nephritis)", section on 'Renal manifestations'.)
Chronic GN Patients who present with chronic GN may have few overt symptoms, and asymptomatic
hematuria or proteinuria discovered on routine urinalysis may be the only presenting sign. In addition, causes
of chronic GN may present as acute nephritic syndrome and may be initially indistinguishable clinically from
acute disorders.
In some cases, patients are diagnosed in a late stage of disease and present with hypertension, renal
impairment, and proteinuria with or without hematuria. The renal biopsy at this stage may only demonstrate
nonspecific and nondiagnostic findings of fibrosis, glomerular sclerosis, and tubular atrophy on light
microscopy. Immunofluorescence microscopy may be more helpful in making a diagnosis.
Chronic GN that presents in childhood includes both primary GN (eg, MPGN, IgA nephropathy, and anti-GBM
disease) and secondary GN (eg, lupus nephritis and granulomatosis with polyangiitis).
Histopathology A renal biopsy sample is often needed to determine the underlying histologic etiology of
glomerulonephritis. However, in some cases (eg, poststreptococcal GN) the diagnosis is made clinically, and
a biopsy is not required. In other cases, the renal biopsy is needed to make or confirm the diagnosis.
The histopathologic evaluation consists of the following:
Light microscopy
Immunofluorescence examination
Electron microscopy
Light microscopy The light microscopic findings generally are not specific, as the same morphological
pattern may be produced by a number of different diseases. As an example, MPGN can be caused by a
variety of systemic immune complex diseases, including infective endocarditis, systemic lupus erythematous,
or hepatitis C viruses, or can be a primary idiopathic disorder. (See "Clinical presentation, classification, and
causes of membranoproliferative glomerulonephritis".)
In addition, a specific disease may present with several different renal histologic patterns. As an example,
lupus nephritis can present as six different histologic patterns on renal biopsy. (See "Diagnosis and
classification of renal disease in systemic lupus erythematosus".)
Minimal mesangial lupus nephritis (class I)

Mesangial proliferative lupus nephritis (class II)
Focal lupus nephritis (class III)
Diffuse lupus nephritis (class IV)
Membranous lupus nephropathy (class V)
Advanced sclerosing lupus nephritis (class VI)
Despite the diagnostic limitation of light microscopy, it is a generally useful tool because histologic findings
often correlate with the clinical status and prognosis of the patient. (See "Glomerular disease: Evaluation and
differential diagnosis in adults".)
Diffuse proliferative glomerulonephritis is associated with inflammatory lesions in most or all of the
glomeruli. Patients may have significant and serious clinical findings, including nephrotic range
proteinuria, edema, hypertension, and renal insufficiency.
Focal glomerulonephritis is associated with inflammatory lesions in less than one-half of the glomeruli. In
contrast to diffuse nephritis, patients with focal involvement generally do not have serious clinical findings
and have a better prognosis.
Immunofluorescence microscopy Immunofluorescence microscopy demonstrates the pattern of

immunoglobulin and complement glomerular deposition, which is helpful in identifying specific renal disorders
among the different causes of GN (algorithm 1).
Linear deposition of IgG along the GBM is diagnostic for anti-GBM GN.
Granular deposits are characteristic of immune complex diseases. The pattern of deposition is based
upon the immunosera used (eg, anti-IgG, anti-IgA, anti-C3), and is used to diagnose specific GN, as
demonstrated by the following examples:
IgA deposition greater than IgG deposition in the mesangium is characteristic for either IgA
nephropathy or IgAV (HSP) nephritis (picture 2).
IgG and C3 deposition that is on the external side of the GBM is characteristic of poststreptococcal
GN (picture 3), whereas IgG and C3 deposition found along the GBM and mesangium is seen in
MPGN types I and III (picture 4).
IgG, mainly IgG1 and IgG3, together with IgA, IgM, C3, C4, and C1q, also called full house, is highly
suggestive of lupus nephritis.
Deposits that only contain C3 without IgG along the glomerular, tubular, and Bowman's capsule
basement membranes, and the mesangium is characteristic of dense deposit disease (MPGN type
II) and C3 glomerulopathy. (See "C3 glomerulopathies: Dense deposit disease and C3
glomerulonephritis".)
Absence of immunoglobulins is characteristic of pauci-immune glomerulonephritis that is seen in patients

with systemic vasculitis, such as granulomatosis with polyangiitis and microscopic polyangiitis. (See
"Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis",
section on 'Renal histology'.)
Electron microscopy Electron microscopy may be useful in confirming or making a specific diagnosis
of an underlying renal disorder. As an example, electron microscopy demonstrates the characteristic
subepithelial "humps" seen in patients with poststreptococcal GN (picture 5). (See "Poststreptococcal
glomerulonephritis".)
SPECIFIC DISORDERS Specific glomerulonephritides in children are divided into primary GN (disease
process isolated to the kidney) or secondary GN (renal disease is a component of a systemic disorder), and
many are discussed individually elsewhere in the program (table 1).
Primary GN
Membranoproliferative glomerulonephritis (see "Clinical presentation, classification, and causes of

membranoproliferative glomerulonephritis")
Immunoglobulin A (IgA) nephropathy (see "Clinical presentation and diagnosis of IgA nephropathy")
Anti-glomerular basement membrane (GBM) disease (see "Pathogenesis and diagnosis of anti-GBM
antibody (Goodpasture's) disease")
Idiopathic crescentic GN (see "Overview of the classification and treatment of rapidly progressive
(crescentic) glomerulonephritis")
Secondary GN
Poststreptococcal GN (see "Poststreptococcal glomerulonephritis")
IgA vasculitis (Henoch-Schnlein purpura) (see "IgA vasculitis (Henoch-Schnlein purpura): Clinical
manifestations and diagnosis" and "Renal manifestations of Henoch-Schnlein purpura (IgA vasculitis)")
Systemic lupus erythematosus nephritis (see "Diagnosis and classification of renal disease in systemic
lupus erythematosus")
Granulomatosis with polyangiitis (formerly called Wegeners granulomatosis) and microscopic

polyangiitis (see "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and
microscopic polyangiitis")
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics"
and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient education: Glomerular disease (The Basics)")
SUMMARY AND RECOMMENDATIONS Glomerulonephritis (GN) generally presents as a constellation of

findings that include hematuria, proteinuria, edema, and often hypertension. It is caused by a number of
disorders that are all characterized by glomerular injury accompanied by inflammation.
The pathogenesis of GN is not fully understood. Currently available data suggest that most cases of GN
are due to an immunologic response to a variety of different etiologic agents. The immunologic response,
in turn, activates a number of biological processes (eg, complement activation, leukocyte recruitment,
and release of growth factors and cytokines), which result in glomerular inflammation and injury. (See
'Pathogenesis' above.)
Because the differential diagnosis for GN is broad, using a classification schema is helpful to narrow the
causes of GN in a systematic manner. The etiology of glomerulonephritis in children can be classified by
its clinical presentation (acute GN, rapidly progressive GN, recurrent macroscopic hematuria, and
chronic GN) or by histopathology. The histologic findings are based upon light, immunofluorescence, and
electron microscopy. (See 'Etiologic classification' above.)
GN may be isolated to the kidney (primary glomerulonephritis) or be a component of a systemic disorder

(secondary glomerulonephritis) (table 1). Specific causes of GN in children are discussed in separate
reviews found elsewhere in the program. (See 'Specific disorders' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. Chadban SJ, Atkins RC. Glomerulonephritis. Lancet 2005; 365:1797.

2. Couser WG. Pathogenesis of glomerulonephritis. Kidney Int Suppl 1993; 42:S19.
3. Hellmark T, Burkhardt H, Wieslander J. Goodpasture disease. Characterization of a single
conformational epitope as the target of pathogenic autoantibodies. J Biol Chem 1999; 274:25862.
4. Wu J, Hicks J, Borillo J, et al. CD4(+) T cells specific to a glomerular basement membrane antigen
mediate glomerulonephritis. J Clin Invest 2002; 109:517.
5. Nangaku M. Complement regulatory proteins in glomerular diseases. Kidney Int 1998; 54:1419.
6. Kilgore KS, Schmid E, Shanley TP, et al. Sublytic concentrations of the membrane attack complex of
complement induce endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear
factor-kappa B activation. Am J Pathol 1997; 150:2019.
7. Hughes J, Nangaku M, Alpers CE, et al. C5b-9 membrane attack complex mediates endothelial cell
apoptosis in experimental glomerulonephritis. Am J Physiol Renal Physiol 2000; 278:F747.
8. Atkins RC, Nikolic-Paterson DJ, Song Q, Lan HY. Modulators of crescentic glomerulonephritis. J Am
Soc Nephrol 1996; 7:2271.
9. Rodriguez-Iturbe B. Postinfectious glomerulonephritis. Am J Kidney Dis 2000; 35:XLVI.
10. Zhang Y, Shen Y, Feld LG, Stapleton FB. Changing pattern of glomerular disease at Beijing Children's
Hospital. Clin Pediatr (Phila) 1994; 33:542.
11. Sanjad S, Tolaymat A, Whitworth J, Levin S. Acute glomerulonephritis in children: a review of 153
cases. South Med J 1977; 70:1202.
Topic 6117 Version 19.0
GRAPHICS
Causes of glomerulonephritis in children
Primary glomerulonephritis
Membranous glomerulonephritis
Membranoproliferative glomerulonephritis type I
Membranoproliferative glomerulonephritis type II (dense deposit disease)
IgA nephropathy
Anti-glomerular basement membrane disease
Idiopathic crescentic glomerulonephritis
Secondary glomerulonephritis
Post-streptococcal glomerulonephritis
Other post-infectious glomerulonephritis
Henoch-Schnlein purpura nephritis
Systemic lupus erythematosus nephritis
Microscopic polyangiitis
Wegener granulomatosus
Original figure modified for this publication. Reproduced with permission from: Niaudet P. Nephritic Syndrome. In:
Comprehensive Pediatric Nephrology, Geary DF, Schaefer F (Eds), Mosby, Philadelphia 2008. Illustration used with
the permission of Elsevier Inc. All rights reserved.
Graphic 52094 Version 2.0
Mechanisms of glomerular damage
Schematic depiction of the major mechanisms by which immune events lead

to capillary wall damage and proteinuria.
GEC: glomerular epithelial cells; GEN: glomerular endothelial cells; MC: mesangial
cells; PMNs: polymorphonuclear cells.
https://www.uptodate.com/contents/overview-of-the-pathogenesis-arce=search_result&search=glomerulonephritis&selectedTitle=1~150 Page 10 of 23
Bacterial and viral agents associated with post-infectious glomerulonephritis
Bacterial infections
Skin or throat (Streptococcus group A)
Endocarditis (Staphylococcus aureus, Streptococcus viridans)
Visceral abcess (Staphylococcus aureus, E. coli, Pseudomonas, Proteus mirabilis)
Shunt nephritis (Staphylococcus aureus, Staphylococcus albus, Streptococcus viridans)
Pneumonia (Diplococcus pneumoniae, Mycoplasma)
Typhoid fever (Salmonella typhi)
Viral infections
Epstein Barr virus
Parvovirus B19
Varicella
Cytomegalovirus infection
Coxsackie
Rubella
Mumps
Hepatitis B
Parasitic infections
Schistosoma mansoni
Plasmodium falciparum
Toxoplasma gondii
Filaria
Original figure modified for this publication. Reproduced with permission from: Niaudet P. Nephritic Syndrome. In:
Comprehensive Pediatric Nephrology, Geary DF, Schaefer F (Eds), Mosby, Philadelphia 2008. Illustration used with
the permission of Elsevier Inc. All rights reserved.
Light micrograph showing crescentic glomerulonephritis
High-power light micrograph in crescentic glomerulonephritis. The

hypercellular circumferential crescent (arrows) is compressing the glomerular
tuft in the center of the glomerulus and closing the capillary lumens.
Courtesy of Helmut Rennke, MD.
Normal glomerulus
Light micrograph of a normal glomerulus. There are only 1 or 2 cells per

capillary tuft, the capillary lumens are open, the thickness of the
glomerular capillary wall (long arrow) is similar to that of the tubular
basement membranes (short arrow), and the mesangial cells and
mesangial matrix are located in the central or stalk regions of the tuft
(arrows).
Courtesy of Helmut G Rennke, MD.
Light micrograph showing crescentic glomerulonephritis

II
High-power light micrograph showing an active hypercellular crescent

containing fibrin, which has a bright red appearance (long arrow). Note that
the severe inflammatory injury has led to fragmentation of the glomerular
tuft (short arrow) and to creation of a rent in the capsule (double arrow).
Normal glomerulus
Light micrograph of a normal glomerulus. There are only 1 or 2 cells per

capillary tuft, the capillary lumens are open, the thickness of the
glomerular capillary wall (long arrow) is similar to that of the tubular
basement membranes (short arrow), and the mesangial cells and
mesangial matrix are located in the central or stalk regions of the tuft
(arrows).
Immunofluorescence microscopy showing linear IgG
Immunofluorescence microscopy showing characteristic linear deposition of

IgG in anti-GBM antibody disease.
IgG: immunoglobulin G; GBM: glomerular basement membrane.
Immunofluorescence microscopy showing fibrin

deposition
Immunofluorescence microscopy showing intense deposition (bright areas in

the upper right portion of the glomerulus) of fibrin within a circumferential
crescent surrounding the glomerular tuft in any form of crescentic or rapidly
progressive glomerulonephritis, including that due to anti-GBM antibody
disease.
GBM: glomerular basement membrane.
Electron micrograph in crescentic glomerulonephritis
Electron micrograph in rapidly progressive glomerulonephritis (RPGN)

showing characteristic breaks in the glomerular basement membrane (GBM)
(arrows). These rents allow fibrin and cellular elements to enter Bowman's
space and initiate crescent formation.
Electron micrograph of a normal glomerulus
Electron micrograph of a normal glomerular capillary loop showing the

fenestrated endothelial cell (Endo), the glomerular basement membrane
(GBM), and the epithelial cells with its interdigitating foot processes
(arrow). The GBM is thin, and no electron-dense deposits are present.
Two normal platelets are seen in the capillary lumen.
Use of serologic testing and immunofluoresence microscopy in the diagnosis

of glomerulonephritis in children
GN: glomerulonephritis; GBM: glomerular basement membrane; ANCA: antineutrophil cytoplasmic antibodies;
IFM: immunofluorescent microscopy; Ig: immunoglobulin; MPGN: membranoproliferative glomerulonephritis;
SLE: systemic lupus erythematous; HSP: Henoch-Schnlein purpura.
Reproduced with permission from: Niaudet P. Nephritic Syndrome. In: Comprehensive Pediatric Nephrology,
Geary DF, Schaefer F (Eds), Mosby, Philadelphia 2008. Illustration used with the permission of Elsevier Inc. All
rights reserved.
Immunofluorescence microscopy showing mesangial

immunoglobulin A (IgA) deposits
Immunofluorescence microscopy demonstrating large, globular mesangial

IgA deposits that are diagnostic of IgA nephropathy or Henoch-Schnlein
purpura (IgA vasculitis). Note that the capillary walls are not outlined since
the deposits are primarily limited to the mesangium.
Postinfectious glomerulonephritis
Immunofluorescence microscopy shows granular deposition of complement in

the glomerular tuft in postinfectious glomerulonephritis. Immunoglobulin G
(IgG) can also be seen in the same distribution.
Rim immunofluorescent pattern in membranoproliferative

glomerulonephritis
Immunofluorescence microscopy in membranoproliferative

glomerulonephritis reveals complement deposition in a rim pattern outlining
the glomerular capillary wall.
Electron micrograph of postinfectious glomerulonephritis
Electron micrograph shows subepithelial deposits (D) with a semilunar,

hump-shaped appearance in postinfectious glomerulonephritis. The humps
sit on top of the glomerular basement membrane (GBM). A neutrophil is
attached to the denuded GBM, contributing to the glomerular inflammation.
Neutrophil attraction requires the initial presence of subepithelial immune
deposits so that complement chemoattractants have access to the systemic
circulation.
Electron micrograph of a normal glomerulus
Electron micrograph of a normal glomerular capillary loop showing the

fenestrated endothelial cell (Endo), the glomerular basement membrane
(GBM), and the epithelial cells with its interdigitating foot processes
(arrow). The GBM is thin, and no electron-dense deposits are present.
Two normal platelets are seen in the capillary lumen.
Contributor Disclosures
Patrick Niaudet, MD Nothing to disclose F Bruder Stapleton, MD Nothing to disclose Melanie S Kim,
MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
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Overview of the pathogenesis and causes of glomerulonephritis in children - UpToDate 08/12/17 06.

Official reprint from UpToDate

Author: Patrick Niaudet, MD

INTRODUCTION Glomerulonephritis (GN) generally presents as a constellation of findings that include

Leukocyte recruitment A constant feature of GN is the glomerular infiltration of leukocytes (neutrophils,

Clinical presentation The different clinical presentations include:

Rapidly progressive GN Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome

RPGN occurs rarely in children. Causes of pediatric RPGN include:

Recurrent macroscopic hematuria In children, common presentations of IgA nephropathy are

The histopathologic evaluation consists of the following:

Minimal mesangial lupus nephritis (class I)

Immunofluorescence microscopy Immunofluorescence microscopy demonstrates the pattern of

Absence of immunoglobulins is characteristic of pauci-immune glomerulonephritis that is seen in patients

Membranoproliferative glomerulonephritis (see "Clinical presentation, classification, and causes of

Poststreptococcal GN (see "Poststreptococcal glomerulonephritis")

Granulomatosis with polyangiitis (formerly called Wegeners granulomatosis) and microscopic

Basics topics (see "Patient education: Glomerular disease (The Basics)")

SUMMARY AND RECOMMENDATIONS Glomerulonephritis (GN) generally presents as a constellation of

GN may be isolated to the kidney (primary glomerulonephritis) or be a component of a systemic disorder

Use of UpToDate is subject to the Subscription and License Agreement.

1. Chadban SJ, Atkins RC. Glomerulonephritis. Lancet 2005; 365:1797.

Topic 6117 Version 19.0

Causes of glomerulonephritis in children

Membranoproliferative glomerulonephritis type I

Membranoproliferative glomerulonephritis type II (dense deposit disease)

Anti-glomerular basement membrane disease

Idiopathic crescentic glomerulonephritis

Other post-infectious glomerulonephritis

Henoch-Schnlein purpura nephritis

Systemic lupus erythematosus nephritis

Graphic 52094 Version 2.0

Mechanisms of glomerular damage

Schematic depiction of the major mechanisms by which immune events lead

Graphic 52652 Version 3.0

Bacterial and viral agents associated with post-infectious glomerulonephritis

Endocarditis (Staphylococcus aureus, Streptococcus viridans)

Visceral abcess (Staphylococcus aureus, E. coli, Pseudomonas, Proteus mirabilis)

Shunt nephritis (Staphylococcus aureus, Staphylococcus albus, Streptococcus viridans)

Pneumonia (Diplococcus pneumoniae, Mycoplasma)

Typhoid fever (Salmonella typhi)

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Light micrograph showing crescentic glomerulonephritis

High-power light micrograph in crescentic glomerulonephritis. The

Courtesy of Helmut Rennke, MD.

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Light micrograph of a normal glomerulus. There are only 1 or 2 cells per

Courtesy of Helmut G Rennke, MD.

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Light micrograph showing crescentic glomerulonephritis

High-power light micrograph showing an active hypercellular crescent

Courtesy of Helmut Rennke, MD.

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Light micrograph of a normal glomerulus. There are only 1 or 2 cells per

Courtesy of Helmut G Rennke, MD.

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Immunofluorescence microscopy showing linear IgG

Immunofluorescence microscopy showing characteristic linear deposition of

IgG: immunoglobulin G; GBM: glomerular basement membrane.

Courtesy of Helmut Rennke, MD.

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Immunofluorescence microscopy showing fibrin

Immunofluorescence microscopy showing intense deposition (bright areas in