Paediatrics and International Child Health

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Post-infectious glomerulonephritis

Ramnath Balasubramanian & Stephen D. Marks

To cite this article: Ramnath Balasubramanian & Stephen D. Marks (2017) Post-infectious
glomerulonephritis, Paediatrics and International Child Health, 37:4, 240-247, DOI:
10.1080/20469047.2017.1369642

To link to this article: https://doi.org/10.1080/20469047.2017.1369642

Published online: 11 Sep 2017.

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Paediatrics and International Child Health, 2017
VOL. 37, NO. 4, 240–247
https://doi.org/10.1080/20469047.2017.1369642

Post-infectious glomerulonephritis
Ramnath Balasubramaniana and Stephen D. Marksa,b
a
Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; bUniversity College
London Great Ormond Street Institute of Child Health, London, UK

ABSTRACT ARTICLE HISTORY

Post-infectious glomerulonephritis (PIGN) is one of the most common causes of acute Received 20 March 2017
glomerulonephritis in children. Although post-streptococcal glomerulonephritis (PSGN) is still Accepted 16 August 2017
common, there is a wide spectrum of causative agents of PIGN. Non-streptococcal organisms KEYWORDS
are emerging as the main aetiological agents in high-income countries. Nephritis-associated Glomerulonephritis; post-
plasmin receptor (NAPlr) and streptococcal pyrogenic exotoxin B (SPeB) are the two common infectious; paediatrics; acute
antigens implicated in the pathogenesis of PSGN. Both NAPlr and SPeB activate the alternative kidney injury; chronic kidney
complement pathway, resulting in low serum complement levels, and have an affinity to plasmin disease
and glomerular proteins. The clinical presentation of PIGN varies from a benign asymptomatic
condition to rapidly progressive glomerulonephritis requiring dialysis. In most cases, PIGN
is self-limiting and the evidence base for the treatments used is quite weak. Renal biopsy is
indicated when there are atypical features, rapid progression or inadequate recovery, or where
an alternative diagnosis has to be considered. IgA-dominant nephritis, endocarditis-associated
nephritis and shunt nephritis are special sub-subtypes of PIGN. The prognosis is generally
excellent, although long-term follow-up may be needed.

Introduction epidemiological and molecular characteristics of Group A

streptococcal infection in Africa which may provide more
Post-infectious glomerulonephritis (PIGN) is an
valuable data in the future [7]. In high-income countries,
immune-mediated glomerular injury that occurs as
PIGN is now predominantly caused by non-streptococcal
a result of host response to an extra-renal infection
infections [8]. Acute PIGN in high-income countries is pre-
[1]. Several other terms such as acute nephritis, acute
dominantly a disease of the adults with risk factors such
nephritic syndrome and acute glomerulonephritis have
as diabetes, malignancy, alcoholism, human immunode-
also been used to describe the clinical entity but do not
ficiency viral (HIV) infection and intravenous drug use [6].
include the infectious aetiology of the renal injury. PIGN
Despite reduction in the worldwide incidence of PIGN,
is one of the most common causes of acute glomerulone-
epidemics and clusters continue to appear. In LMIC, acute
phritis in children. The epidemiology of PIGN, especially
PIGN frequently causes severe acute kidney injury (AKI),
in high-income countries, has been constantly changing.
requiring dialysis and/or admission for paediatric intensive
Post-streptococcal glomerulonephritis (PSGN) is the clas-
care. The proportion of cases of AKI related to PIGN varies
sic example of this condition and even its epidemiology
from 5.2% in Lima, Peru to 51.6% in Casablanca, Morocco
has changed in the last few decades [2]. The estimated
[9]. Large epidemics of PSGN have been reported in coun-
global incidence is 472,000 cases per year, 77% of which
tries in the middle range of the Human Development Index
are in low- and middle-income countries (LMIC) [3]. It is
(HDI), between 48 and 87 of 177 [9] and clusters of cases
also acknowledged that the incidence has decreased over
in countries in the upper 10% of the HDI. The countries
the last few decades [4,5]. PSGN is less common now in
where PSGN has not been reported in the past 30 years are
high-income countries owing to improved socio-eco-
in the so-called ‘low’ range of the HDI (0.449–0.336), and
nomic status, improved hygiene and possibly the wide-
overwhelming social and health problems in combination
spread use of antibiotics. The burden of disease imposed
with poor documentation resources are likely reasons for
by PSGN remains significant in LMIC with an estimated
the apparent absence of PSGN. In the past 30 yr, most of
incidence of >200 cases/million population/year [6]. Large
the smaller epidemics and clusters of cases are reported
population studies in LMIC are scarce and the true dis-
from poor communities, rural and/or Aboriginal, within
ease burden is unknown. The AFROStrep study is a collab-
countries in the upper 10% range of the HDI.
orative, multicentre study of the clinical, microbiological,

CONTACT  Stephen D. Marks  stephen.marks@gosh.nhs.uk

© 2017 Informa UK Limited, trading as Taylor & Francis Group
 PAEDIATRICS AND INTERNATIONAL CHILD HEALTH   241

Aetiology from rheumatogenic strains which are implicated in

rheumatic fever, although both are immunological com-
PIGN was thought to be almost exclusively post-strep-
plications of streptococcal disease. Certain M types cause
tococcal but there are now reports of a much wider
PSGN, initially inducing an upper respiratory tract infec-
spectrum of infections associated with it (Table 1). The
tion, namely types 1, 2, 4, 12, 18 and 25, while other types
bacterial agents implicated include staphylococcus,
cause pyoderma (types 49, 55, 57 and 60). Evidence now
pneumococcus, a variety of Gram-negative bacteria
indicates that M protein itself is not nephritogenic and a
and intracellular bacteria (chlamydia and mycoplasma).
search for nephritigenic antigens has led to at least two
There are also case reports of viruses (herpes simplex
proteins: nephritis-associated plasmin receptor (NAPlr)
virus, cytomegalovirus, Epstein–Barr virus, mumps, res-
and streptococcal pyrogenic exotoxin B (SPeB). The
piratory syncytial virus, influenza, hepatitis B virus) and
pathogenesis of immune complex-mediated glomeru-
parasites (toxoplasma, Plasmodium malariae) as causa-
lonephritis is summarised in Figure 1.
tive agents [10,11]. However, PSGN accounts for >95%
Both NAPlr and SPeB have been implicated in the
of PIGN cases in children. Group A β-haemolytic strep-
pathogenesis of PSGN, depending on the geographic
tococcus accounts for most of these but epidemics have
location of the study cohort [9]. NAPlr, isolated from
also been caused by group C streptococci [9].
groups A and C streptococci, seems to be the putative
An extensive list of the various agents implicated in
antigen in the Japanese population with serum anti-
PIGN is given in Table 1 but the list may not be com-
bodies to NAPlr detected in 92% of convalescing PSGN
pletely exhaustive [12].
patients and in 60% of patients with uncomplicated
streptococcal infections [14]. Glomerular deposition of
Pathogenesis of post-streptococcal NAPlr occurs early in the course of the disease and is
glomerulonephritis detectable in renal biopsies with PSGN [14], localising
to mesangial cells, endothelial cells and neutrophils [15].
In the early phase of the streptococcal infection, strepto-
NAPlr is a glyceraldehyde-3-phosphate dehydrogenase
coccal antigens enter the bloodstream and localise in the
with plasmin-binding capacity, a nephritogenic prop-
glomerulus. A few days later, antibodies specific to these
erty that aids circulating immune complex deposition
antigens begin to appear in the circulation. The antigens
[16]. NAPlr seems to be less significant outside Japan
planted in the glomerulus now begin to interact with
as NAPlr antibodies or antigens were rarely detected in
the newly formed circulating antibodies to form immune
serum or renal biopsies, respectively, in non-Japanese
complexes in situ. However, the antigens entering the
patients [17].
circulation after the antibody response is fully under way
SPeB seems to be the putative antigen in Latin
have a different fate. These antigens interact with circu-
America, the United States and Europe [18]. It is a cat-
lating antibodies to form circulating immune complexes,
ionic protease with plasmin-binding properties which
some of which are deposited in the glomeruli, adding to
is secreted as an exotoxin and localises to glomeruli in
the glomerular accumulation of immune complexes [13].
PSGN [18,19]. Corresponding serum anti-SPeB antibodies
Several strains of streptococci have been identified
were found in high titres in most or all patients during
and classified as nephritogenic. These are clearly distinct

Table 1. Infectious agents associated with post-infectious glomerulonephritis [adapted from Ref. 27].
Bacterial Viral Fungal Parasites
Streptococcus groups A, C, G Coxsackie virus Coccidioides immitis Plasmodium malariae
Streptococcus viridans Echovirus Plasmodium falciparum
Schistosoma mansoni
Schistosoma haematobium
Toxoplasma gondii
Filariasis
Trichinosis
Staphylococcus (aureus, epidermidis) Cytomegalovirus Trypanosomes
Pneumococcus Epstein–Barr virus
Neisseria meningitidis Hepatitis B, C
Mycobacteria HIV
Salmonella typhi Rubella
Klebsiella pneumoniae Measles
Escherchia coli Varicella
Yersinia enterocolitica Vaccinia
Legionella Parvovirus
Brucella melitensis Influenza
Treponema pallidum Adenovirus
Corynebacterium bovis
Actinobacilli
Bartonella henselae
Orientia tsutsugamushi (scrub typus)
242   R. BALASUBRAMANIAN AND S. D. MARKS
Figure 1.  Pathogenesis of immune complex-mediated
glomerulonephritis [adapted from Ref. 1].
convalescence [20]. Furthermore, SPeB titres correlate
with the presence of nephritis better than either ASO or
anti-DNase B antibodies [21]. Percutaneous renal biop-
sies demonstrate SPeB antigen co-localising with C3 in
sub-epithelial humps.
Although more nephritogenic antigens might yet be
discovered, presently NAPlr and SPeB are the two distinct
antigens with a pathogenicity determined by genetic
background and geography [9]. Both NAPlr and SPeB
activate the alternative complement pathway, resulting
in low serum complement levels, and have affinity to
plasmin and glomerular proteins [19,22]. NAPlr and SPeB
promote formation of circulating immune complexes
which are deposited in sub-endothelium. These nephri-
togenic antigens can induce glomerular inflammation
and local antibody production [9]. SPeB is a superantigen
capable of initiating T-cell activation and proliferation
without being processed by an antigen-presenting cell.
Plasmin activation by NAPlr, SPeB and other streptococ-
cal antigens (streptokinase, enolase) results in glomerular
basement membrane and mesangial matrix degradation
by metalloproteinases and collagenases [9]. In PSGN,
there may also be a role for innate immunity through
lectin pathway activation [22]. Mannose-binding lectin
recognises streptococcal cell wall polysaccharides and
activates the complement pathway, and this mechanism
may be the first line of defence before acquired immunity
(antigen-antibody interaction) becomes effective [23].
Since there is considerable evidence for and against
most putative nephritogenic antigens, collaborative
efforts towards genomic sequencing of nephritogenic
strains of streptococci have been initiated. Discovery of
new nephritogenic antigen candidates may be achieved
by examining conserved and differing regions of the
genome. Such efforts should improve our understand-
ing of the pathogenetic mechanism(s) underlying PSGN
[9,24].
Evidence from serum complement profiles and
immunofluorescence patterns for glomerular deposits
indicates that C3 activation in PSGN is predominately via
the alternative pathway. Initially, some patients may have
classical pathway activation, as evidenced by transient
depression of serum C1q, C2 and/or C4 concentrations
and the presence of circulating C1-inhibitor-C1r-C1s com-
plexes or C4d fragments. These findings of classical com-
plement pathway activation could reflect the presence of
circulating immune complexes in the acute stage which
are distinct from the glomerular immune deposits [24].
Crescentic PSGN may have an increased associa-
tion with normal complement levels. In Memphis, USA,
50% (5 of 10) of patients with crescentic PSGN and, in
New Zealand, 36% (4 of 11) of patients had normal or
near-normal serum complement C3 levels; however,
none of the four reported by Lewy et al. had normal or
near-normal serum C3 levels. The reason for this possible
association of normal complement levels with crescent
formation in PSGN is not clear [25,26].
Clinical features of post-infectious
glomerulonephritis
There is a male preponderance in PSGN. The typical
age at presentation is 4–14  years and it rarely occurs
in children <2 years of age. The latent period between
onset of the primary infection and glomerulonephritis
is about 3–5 weeks for a skin infection and 1–2 weeks
with an upper respiratory tract infection [27,28]. The clin-
ical course has been described to follow one of the fol-
lowing patterns: subclinical, acute nephritic syndrome,
nephrotic syndrome or rapidly progressive glomerulo-
nephritis (RPGN).
The subclinical form is around four or five times more
common than overt glomerulonephritis. Yoshizawa et
al. [29] prospectively collected urine samples from 49
patients who had experienced pharyngeal infections
with Group A streptococci and found that 12 (24%) had
subclinical glomerulonephritis. Among the associated
renal biopsy specimens, 11 (92%) demonstrated histo-
logical abnormalities of the glomeruli, ranging from mild
mesangial hypercellularity to diffuse mesangial prolifer-
ation [29].
Acute nephritic syndrome is the classical presentation
of the PIGN with haematuria (macroscopic in a third of
patients), hypertension (60–80%), oedema (90%) and
oliguria in <50% of patients. It may present as nephrotic
syndrome in 2–4% of patients [27].
Atypical presentations of PSGN include patients with
sub-clinical disease and those presenting with acute
illness, usually related to hypertension or oedema in
the absence of overtly abnormal urine sediment [30].
There are numerous case reports of children who present
with extreme manifestations, usually from hypertensive
crises, and do not display the typical urinary findings at
presentation [30]. Serial examination of urine after pres-
entation may eventually confirm the suspicion of acute
glomerulonephritis.

Table 2. Consider alternative diagnosis when the following are
present [adapted from Ref. 27].
Normal complement level: rule out IgA nephropathy
Low complement level after 1–2 months: consider SLE, MPGN
Nephrotic-range proteinuria
Rising proteinuria, RPGN
Age <2 years
Extra-renal manifestations
Another atypical feature of PSGN at presentation is
the presence of a typical Henoch–Schönlein purpura
(HSP) rash of IgA vasculitis [31–33]. The diagnosis of
PSGN was confirmed by renal biopsy in those cases.
An alternative diagnosis needs to be considered seri-
ously in certain situations (Table 2).
Anti-streptolysin O titre
The serological markers most commonly used to iden-
tify streptococcal infection as the trigger of PSGN are
anti-streptolysin O (ASO) titre and depression of serum
complement C3 level. Increased levels of antibody to
anti-streptococcal antigens [ASO, anti-hyaluronidase
(A-H) and anti-DNAase] are documented less often than
low levels of complement C3. ASO titres are higher in
pharyngitis-associated PSGN than pyoderma-associ-
ated PSGN [34–36]. In an early study, the sensitivity of
an elevated ASO titre was extremely high (97%), but the
specificity was only 80%, presumably because up to 20%
of unaffected controls demonstrated evidence of strep-
tococcal exposure with a significantly elevated titre [37].
Early descriptions of the time course for increasing ASO
and A-H titres show that in a group of patients with typ-
ical PSGN (previously known as type A acute glomerulo-
nephritis), ASO was increased above normal in 72% [38].
In a series of biopsy-proven cases from Memphis, USA,
60% had elevated ASO titres defined by Todd units > 333
[26]. Cases following pyoderma are more likely to have
a raised anti-DNAase B titre than an elevated ASO titre
[38,39]. In children whose initial ASO titre is normal,
subsequent measurements may be elevated, thus sup-
porting the suspected diagnosis. This was demonstrated
by Dodge et al. who found that the ASO titre contin-
ued to increase over the 4 weeks after presentation in
some cases and the mean titre peaked at 3 weeks [39].
In addition, performance of more than one streptococcal
antibody test increased the number of individuals with
‘positive’ titres ranging from 80 to 95% [35]. Travis et al.
tested for ASO, A-H and anti-DNAse in 60 patients and
found that ASO was often negative while anti-DNAse
and/or A-H were positive [40].
Complement C3 levels
The acute reduction of serum complement C3 concen-
tration in PSGN with the typical return to normal levels
within 6 weeks of onset is of foremost diagnostic impor-
tance when renal biopsy is not performed [38,41–43].
PAEDIATRICS AND INTERNATIONAL CHILD HEALTH   243
Depression of serum C3 in PSGN has been shown to
precede the onset of haematuria [38,44].
Recovery
The recovery phase occurs after resolution of fluid over-
load with diuresis, either spontaneous and/or pharma-
cologically induced, along with normalisation of blood
pressure and resolution of proteinuria and macroscopic
haematuria. In most case series, the proteinuria disap-
pears much earlier than the microscopic haematuria
[37,45] except for a study by Travis et al. who described the
opposite [40]. During this phase, complement C3 returns
to normal in most affected children. PSGN has occurred
in patients previously diagnosed (by biopsy) with IgA
nephropathy [46,47]. IgA nephropathy is the most com-
mon type of chronic glomerulonephritis and is often undi-
agnosed; the association with PSGN is most likely a chance
occurrence of the two conditions in the same individual.
Recurrence
Second attacks of PSGN have been reported but are rare
[47–50]. In earlier reports, PSGN was pyoderma-associ-
ated in both attacks in most instances [47–49], while the
two case reports since 2000 were both associated with
pharyngitis [50,51]. A recent case series reported two
recurrences of PSGN but the route of infection was not
specified [52].
Pathology of post-streptococcal
glomerulonephritis
The glomerular hypercellularity in PSGN is typically
diffuse and global. In the early phases, glomerular
neutrophils predominate, resulting in an ‘exudative’
appearance [28]. Subsequently, the proportions of lym-
phocytes and monocytes increase along with mesangial
and endocapillary hypercellularity [27,28]. The glomeruli
are enlarged and demonstrate a lobular configuration,
but the basement membranes are of normal thickness
without reduplication. Glomerular fibrinoid necrosis and
cellular crescents are rare but can be prominent in the
setting of clinical RPGN [28]. The characteristic ‘sub-ep-
ithelial humps’ of PSGN can sometimes be visualised
with trichrome stain under oil immersion. In biopsies
performed very early or late in the course of disease,
the glomerular hypercellularity is usually only focal and
segmental [29,30]. Late biopsies representing resolv-
ing PSGN demonstrate only mesangial hypercellularity
with patent capillary loops [27,31]. The extent of acute
tubular injury and tubular protein resorption droplets
vary according to the severity of renal dysfunction and
proteinuria. Interstitial oedema and inflammation is
usually mild. However, interstitial and tubular neutro-
phil infiltrate is sometimes quite prominent, especially
in ‘exudative’ GN [31]. Chronic tubule-interstitial damage
244   R. BALASUBRAMANIAN AND S. D. MARKS
is not a typical feature of PSGN and may indicate prior
glomerular crescents, age-related changes or hyper-
tensive nephrosclerosis. Arteritis is unusual and should
prompt investigation of other types of glomerulone-
phritis or vasculitis. Indications for biopsy in the early
and recovery stages are summarised in Table 3. Timing
of biopsy is key as the pathological features are quite
different when biopsy is performed early (<2 weeks from
onset) or late (>4–6 weeks after onset). These features are
summarised in Table 4.
Treatment
Kidney disease improving global outcomes (KDIGO)
states: ‘poststreptococcal GN is the prototypical infec-
tion-related acute GN. Although classic PSGN occurs
1–3  weeks after the initial clinical manifestations of
pharyngitis or impetigo, affected individuals should
be treated with penicillin (or erythromycin, if penicil-
lin-allergic) even in the absence of persistent infection
to decrease the antigenic load. The nephritic syndrome
should be treated with fluid and supportive manage-
ment which include diuretics, anti-hypertensives and
renal replacement therapy with dialysis, if necessary’.
In most cases, PIGN caused by agents other than strep-
tococcus is self-limiting and the evidence base for the
treatments used is quite weak [53].
Antimicrobials for prophylaxis of PSGN
The effects of different antimicrobials (such as cephalo-
sporin) administered for 5 days vs penicillin V for 10 days
during streptococcal infections as a preventive measure
against onset of PSGN were evaluated in four trials. Two
Table 3. Indications for biopsya [adapted from Ref. 27].
Early stage phase
• Rapid progressive course
• Hypertension >2 weeks
• Depressed GFRb >2 weeks
• Normal complement levels
• Non-significant titres of antistreptococcal antibodies
• Extra-renal manifestations
• Nephrotic syndrome
In recovery
• Depressed GFR >4 weeks
• Hypocomplementaemia >12 weeks
• Persistent proteinuria >6 months
• Persistent microscopic haematuria >18 months
a
Vary, depending on the stage of the disease process when it is considered.
b
GFR, glomerular filtration rate.
Table 4. Timing of biopsy and pathological features [adapted from Ref. 1].
Early biopsy (<2 weeks)
Clinical features Mild albuminuria and haematuria
Light microscopy Glomerular endocapillary proliferation may
be focal and segmental
Immunofluorescence C3 and IgG, starry sky pattern
Electron microscopy Mesangial, sub-epithelial
(humps) ± deposits
randomised controlled trials assessed cefuroxime for
5 days vs penicillin V for 10 days and, after 6–7 weeks of
follow-up, found no significant difference in the risk of
developing PSGN [54,55]. However, antibiotic prophy-
laxis is not generally necessary as PSGN usually resolves
without eradication of the infectious insult, and recur-
rence is rare [9].
Anti-hypertensive agents
One trial assessed the efficacy of anti-hypertensive treat-
ment with nifedipine vs placebo and there was good
control of blood pressure with nifedipine [56]. However,
one trial that assessed hypertension and oedema during
PSGN treated with furosemide showed better results than
with reserpine [57]. Moreover, another trial assessed cap-
topril vs reserpine-furosemide for hypertension during
PSGN and showed significantly better control of supine
and standing blood pressure with ACE inhibitors [58].
Yet another trial assessed echocardiographic changes
in patients treated with enalapril or beta-blockers, vas-
odilators, diuretics and central acting agents (given if
required) for hypertension during PSGN, and results were
better after 6–8 weeks of ACE inhibitors [59].
Immunosuppressants
Corticosteroids are suggested for severe crescentic GN
based on anecdotal evidence only [60]. Only one trial has
investigated the effectiveness of immunosuppressant
drugs. Quintuple therapy comprising immunosuppres-
sion with prednisone, azathioprine and cyclophos-
phamide, also dipyridamole and heparin followed by
warfarin was compared with supportive treatment alone
for biopsy-documented crescentic PSGN and supportive
treatment alone; no clinical advantages in outcome of
the former over the latter were demonstrated [61].
Prevention
There is no global agreement on clinical management
of pharyngitis in children in high-income countries.
Guidelines on diagnosis and treatment usually include
adults as well as children and differ considerably
between countries and continents. There are roughly
two different positions: current guidelines in Belgium,
the Netherlands, Germany and the UK suggest that
Typical features Late biopsy (>4–6 weeks)
Acute nephritic syndrome Persistent haematuria and/or
proteinuria
Diffuse global proliferation (‘exuda- Mesangial proliferation
tive’ early on; lymphocytes, mono-
cytes + mesangial and endothelial
proliferation predominate later)
C3 and IgG, starry sky or garland pattern C3 ± IgG, mesangial pattern
Mesangial, sub-epithelial (humps), Mesangial ± rare sub-epithelial
and ± sub-endothelial deposits humps in the mesangial ‘notch’

diagnosis and treatment of GAS pharyngitis are not nec-
essary unless patients are ‘at risk’ of complications (e.g.
immunocompromised or with a history of acute renal
failure), severely ill or in streptococcus epidemics [62].
The authors of these guidelines assume that streptococ-
cal pharyngitis in high-income countries is nowadays
self-limiting and does not require a specific diagnosis
or antibiotic treatment, unless in high-risk patients, as
mentioned above [62]. In contrast, guidelines by the six
large North American medical societies (i.e. American
Academy of Paediatrics, American Heart Association,
Infectious Diseases Society of America, Institute for
Clinical System Improvement) and the French, Spanish,
Polish, Canadian and Finnish national guidelines do rec-
ommend treatment of (proven) GAS pharyngitis. The
rationale is primarily the prevention of acute rheumatic
fever – possibly re-emerging in high- and middle-income
countries – and other complications [62].
Special sub-types of post-infectious nephritis
Endocarditis-associated glomerulonephritis
Fortunately, endocarditis-associated nephritis is quite
rare in children, mainly because of effective antibiotic
therapy. It was previously seen in subacute infection
by relatively less virulent types of streptococci such as
Streptococcus viridans. The chronic nature of the bacte-
raemia was an ideal environment to produce an anti-
body response and formation of circulating immune
complexes. Endocarditis-associated GN is now usually
restricted to high-risk populations such as adult IV drug
abusers. Data on children are limited and mainly consist
of case reports of severe acute kidney injury and cres-
centic nephritis treated with immunosuppressants [1].
IgA-dominant post-infectious nephritis
In adult studies, IgA-dominant PIGN is accepted as a
variant of PIGN with sole or dominant glomerular IgA
staining along with C3. The most infectious organism
isolated is staphylococcus.
In children, the important considerations are IgA
nephropathy and HSP or IgA vasculitis. IgA nephropa-
thy can be triggered by gastro-intestinal or respiratory
infections. In both IgA nephropathy and vasculitis (HSP
nephritis), the onset of nephritis is ‘synpharyngitic’ with
no interval between the onset of infection and the
nephritis. The correlation of the clinical picture and the
biopsy findings are paramount in identifying this sub-
type of acute nephritis [1].
Shunt nephritis
Shunt nephritis was much more common when ventricu-
lo-atrial shunts were inserted for hydrocephalus. The inci-
dence of shunt infection was as high as 27% with a 2%
PAEDIATRICS AND INTERNATIONAL CHILD HEALTH   245
incidence of glomerulonephritis. The incidence is much
lower with ventriculo-peritoneal shunts. It is thought
to be an immunological reaction with activation of the
classical complement pathway. Staphylococcus aureus
and Staphylococcus epidermidis are commonly found in
these children. Treatment involves appropriate antibiotic
therapy and sometimes removal of the infected shunt [1].
Prognosis
In a 7-year follow-up study of children with acute glo-
merulonephritis in Iran, none had hypertension or renal
impairment. Proteinuria was present in 3.1% of patients
and microscopic haematuria in 6.3% [63]. In a 10-year
follow-up study of Brazilian children with PSGN, hyper-
tension was twice more prevalent in those with PSGN
than in controls. There was no significant difference in
renal function, haematuria or proteinuria [64]. Isolated
microscopic haematuria might, however, continue for
some months [65]. In the 2000s, about 20% of children
followed for 15–18 years showed persisting urine abnor-
malities; however, renal failure was very rare (<1%) [9].
On the other hand, children in LMIC usually have more
severe disease and therefore a poorer prognosis: at pres-
entation, about 30% have acute kidney injury requiring
dialysis and <30% of these children recover fully [9,14,65].
Longer-term studies of outcome in children with PIGN
are scarce but the overall long-term prognosis is excel-
lent. We recommend yearly follow-up after complete
recovery to look for evidence of hypertension, protein-
uria or renal impairment.
Conclusions
Post-infectious glomerulonephritis remains a major
cause of acute glomerulonephritis in children. The epi-
demiology is changing, and non-streptococcal agents
are increasingly implicated in high-income countries.
Multiple streptococcal antigens have been identified
and immune complex deposition is the most accepted
pathological mechanism of the condition. The spectrum
of presentation is varied and the evidence base for some
of the drugs used to treat the condition remains poor,
including antibiotics, antihypertensives and immuno-
suppressants. The outcome of PIGN is usually excellent,
as is the prognosis for renal recovery.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
The project was supported by the National Institute for Health
Research, Biomedical Research Centre at Great Ormond Street
Hospital for Children NHS Foundation Trust and University
College London.
246   R. BALASUBRAMANIAN AND S. D. MARKS
Notes on contributors
Ramnath Balasubramanian is a specialist registrar in
Paediatric Nephrology at Great Ormond Street Hospital for
Children NHS Foundation Trust completing his training to
become a paediatric nephrologist.
Stephen D. Marks is a reader and consultant in Paediatric
Nephrology at University College London Great Ormond
Street Institute of Child Health. His research interests are in
glomerulonephritis, including systemic lupus erythematosus,
vasculitis, renovascular hypertension and paediatric renal
transplantation.
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