Poststreptococcal Glomerulonephritis - UpToDate

23/7/2017 Poststreptococcal glomerulonephritis - UpToDate
Official reprint from UpToDate

www.uptodate.com 2017 UpToDate
Poststreptococcal glomerulonephritis
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: Jun 2017. | This topic last updated: Oct 31, 2016.
INTRODUCTION Poststreptococcal glomerulonephritis (PSGN) is caused by prior infection with specific

nephritogenic strains of group A beta-hemolytic streptococcus. The clinical presentation of PSGN varies from
asymptomatic, microscopic hematuria to the full-blown acute nephritic syndrome, characterized by red to
brown urine, proteinuria (which can reach the nephrotic range), edema, hypertension, and acute kidney
injury. The prognosis is generally favorable, especially in children, but in some cases, the long-term prognosis
is not benign.
The clinical manifestations, diagnosis, management, course of disease, and prognosis of PSGN will be
reviewed here. Evaluation and causes of other glomerular disease in children are discussed separately. (See
"Evaluation of a child with glomerular disease" and "Overview of the pathogenesis and causes of
glomerulonephritis in children".)
EPIDEMIOLOGY Although PSGN continues to be the most common cause of acute nephritis in children
globally, it primarily occurs in developing countries. Of the estimated 470,000 new annual cases of PSGN
worldwide, 97 percent occur in regions of the world with poor socioeconomic status, with an annual incidence
that ranges from 9.5 to 28.5 per 100,000 individuals [1,2].
In more developed and industrialized countries, the incidence has continued to decrease from the 1970s to
the 1990s [2-4]. Based upon data from the Italian Registry of Renal Biopsies, the estimated annual incidence
was 0.3 per 100,000 individuals between 1992 and 1994 [5]. The reasons may include the easier access to
the treatment of streptococcal infections and the widespread presence of fluoride in water, which decreases
virulence factors of Streptococcus pyogenes [6].
The risk of PSGN is increased in older patients (greater than 60 years of age) and in children between 5 and
12 years of age [5,7]. PSGN is uncommon in children less than three years of age. PSGN is twice as
frequent in males as in females [8,9].
PSGN can present as a sporadic case or during an epidemic of group A streptococcal (GAS) infection (ie,
skin and throat infections) [2]. The incidence of clinically detectable PSGN in children infected during a GAS
epidemic is approximately 5 to 10 percent with pharyngitis and 25 percent with skin infections [10,11].
PATHOGENESIS PSGN appears to be caused by glomerular immune complex disease induced by

specific nephritogenic strains of group A beta-hemolytic streptococcus (GAS). The resulting glomerular
immune complex disease triggers complement activation and inflammation. (See "Mechanisms of immune
injury of the glomerulus" and "Overview of the pathogenesis and causes of glomerulonephritis in children",
section on 'Pathogenesis'.)
The following are proposed mechanisms for the immunologic glomerular injury induced by GAS infection [12]:
Deposition of circulating immune complexes with streptococcal antigenic components.
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In situ glomerular immune complex formation promoted by antibodies to streptococcal antigens that
cross-react with glomerular components (molecular mimicry).
Autoimmune reactivity:
Anti-immunoglobulin G (IgG) reactivity has been reported in patients with acute PSGN. For
example, anti-IgG glomerular deposits have been detected in renal biopsy specimens and anti-IgG
activity have been found in eluates from a kidney of patient with a fatal case of the disease [12].It is
postulated that modification by streptococcal neuraminidase may modify immunoglobulins,

rendering them autoantigenic. This proposed mechanism is supported by the finding of
neuraminidase activity and free sialic acid levels in plasma of patients with PSGN [13].
Anti-DNA antibodies, anti-C1q antibodies, and antineutrophil cytoplasmic antibodies (ANCA) may
also be found in some patients [14].
Rheumatic factor are detected in two-thirds of patients with PSGN.
Available evidence suggests that the major pathogenetic mechanism is in situ immune complex
formation due to deposition of streptococcal nephritogenic antigens within the glomerulus [12]. In animal
models of post-infectious glomerulonephritis, injected cationic proteins (histones) but not preformed
immune complexes were detected in the subepithelial deposits (humps) from renal tissue [15].
Nephritogenic antigens There are two leading candidates for the putative streptococcal antigen(s)
responsible for PSGN [12]:
Nephritis-associated plasmin receptor (NAPlr), a glycolytic enzyme, which has glyceraldehyde-3-

phosphate dehydrogenase (GAPDH) activity [16,17]. NAPlr has a plasmin-like activity which may
promote a local inflammatory reaction. An elevated urinary plasmin activity has been observed in
patients with acute PSGN [18].
Streptococcal pyogenic exotoxin B (SPE B), a cationic cysteine proteinase, has been localized in the
subepithelial deposit [19,20]. Results from the following studies provide support for the role of these
proteins in the pathogenesis of PSGN:
In a study of Japanese patients with PSGN, NAPlr was present in renal biopsy samples obtained
within the first 14 days of their disease [16]. Antibodies to NAPlr were present in the sera of 92
percent of patients with PSGN, and 60 percent of patients with uncomplicated GAS infections.
In another report that included patients from Latin America and Switzerland, SPE B was found in 12
of 17 biopsies. SPE B deposition colocalized with complement deposition and within the
subepithelial electron dense deposits (humps) that are characteristic of PSGN (picture 1) [21].
Antibodies to SPE B were detected in the convalescent sera in all 53 patients who were tested. In
contrast, circulating antibodies to NAPlr were found in only 5 of 47 tested sera, and in only one
biopsy sample.
Although the findings from the last study support the role of SPE B as the more likely nephritogenic antigen,
an alternate explanation is that separate antigens are responsible for PSGN in different parts of the world
and/or in patients with varying genetic backgrounds [2,12].
Independent of the immune response, both SPE B and NAPlr can activate the alternate complement pathway
(a characteristic finding in PSGN) and enhance the expression of adhesion molecules. SPE B also can
stimulate the production of chemotactic cytokines [2]. (See 'Complement' below.)
PATHOLOGY
Light microscopy Light microscopy shows a diffuse proliferative glomerulonephritis with prominent
endocapillary proliferation and numerous neutrophils (picture 2 and picture 3). Trichrome stain may show
small subepithelial hump-shaped deposits. The severity of involvement varies and usually correlates with the
clinical findings. Patients who are asymptomatic or have mild disease may have biopsies that show little
glomerular involvement, whereas patients with diffuse endocapillary proliferative glomerulonephritis are more
likely to have full-blown acute nephritic syndrome (ie, red to brown urine, proteinuria, edema, hypertension,
and acute renal failure). Crescent formation is uncommon and is associated with a poor prognosis.
Immunofluorescence microscopy Immunofluorescence (IF) microscopy reveals a characteristic pattern

of deposits of immunoglobulin G (IgG) and C3 distributed in a diffuse granular pattern within the mesangium
and glomerular capillary walls (picture 4) [22].The granular pattern of C3 deposition in the capillary walls

(garland-type deposits) gives a "starry sky" pattern [23]. Other immune reactants (eg, immunoglobulin
M
[IgM], immunoglobulin A [IgA], fibrin, and other complement components) may also be detected.
Electron microscopy The most characteristic feature detected by electron microscopy (EM) are the
dome-shaped subepithelial electron-dense deposits that are referred to as humps (picture 1) [24]. These
deposits along with subendothelial deposits are immune complexes and correspond to the deposits of IgG
and C3 found on IF [22].
Subendothelial immune deposits and subsequent complement activation are responsible for the local
influx of inflammatory cells, leading to a proliferative glomerulonephritis, an active urine sediment, and a
variable decline in glomerular filtration rate (GFR) [25].
Subepithelial "humps" are responsible for epithelial cell damage and proteinuria, similar to that seen in
membranous nephropathy [26]. (See "Causes and diagnosis of membranous nephropathy".)
It has been proposed that the clinical course of PSGN is related to the different rates of clearance of immune
complexes at these two sites. (See 'Correlation with histologic recovery' below.)
CLINICAL MANIFESTATIONS
Clinical presentation The clinical presentation varies from asymptomatic, microscopic hematuria to the
full-blown acute nephritic syndrome, characterized by red to brown urine, proteinuria (which can reach the
nephrotic range), edema, hypertension, and an elevation in serum creatinine [8,27,28]. However, most
children are asymptomatic, as illustrated by a study of 248 children with group A streptococcal (GAS)
infection, of whom 20 developed urinary abnormalities and a transient decrease in serum complement
activity, but only one of whom was clinically symptomatic [28]. A course of rapidly progressive ("crescentic")
glomerulonephritis occurs in less than 0.5 percent of cases [29].
There is usually an antecedent history of a GAS skin or throat infection [7,27,28]. The latent period between
GAS infection and PSGN is dependent upon the site of infection: between one and three weeks following
GAS pharyngitis and between three and six weeks following GAS skin infection [30].
The following symptoms are the most common presenting signs in children [8,27,28,31]:
Edema Generalized edema is present in approximately two-thirds of patients due to sodium and water
retention. In severe cases, fluid overload leads to respiratory distress due to pulmonary edema.
Gross hematuria Gross hematuria is present in approximately 30 to 50 percent of patients. The urine
looks smoky, and tea or cola colored.
Hypertension Hypertension is present in 50 to 90 percent of patients and varies from mild to severe. It
is primarily caused by salt and fluid retention. Hypertensive encephalopathy is an uncommon but serious
complication. Magnetic resonance imaging (MRI) may show posterior reversible leukoencephalopathy
[32]. These patients require emergent intervention. (See "Approach to hypertensive emergencies and
urgencies in children", section on 'Hypertensive encephalopathy' and "Management of hypertensive
emergencies and urgencies in children".)
Subclinical cases of PSGN are primarily characterized by microscopic hematuria [28,33,34]. Such
patients were often detected during epidemics.
Some patients present with clinical symptoms related to hypertensive crisis or edema with minor urine
abnormalities [35].
Laboratory findings
Renal function PSGN is associated with a variable decline in glomerular filtration rate (GFR) that is
detected by a rise in serum creatinine. Acute renal failure requiring dialysis is uncommon. (See "Acute kidney

injury in children: Clinical features, etiology, evaluation, and diagnosis".)
Urinalysis and urinary protein excretion The urinalysis in patients with PSGN reveals hematuria
(some of the red cells are typically dysmorphic) with or without red blood cell casts (picture 5A-C), varying
degrees of proteinuria, and often pyuria. Nephrotic range proteinuria (defined as 1000 mg/m2 per day or 40
mg/m2 per hour) is uncommon and occurs in approximately 5 percent of cases at presentation [36]. The
urinalysis should be performed on a freshly voided specimen.
Complement In approximately 90 percent of patients, C3 and CH50 (total complement activity) are
significantly depressed in the first two weeks of the disease course [37,38]. C4 and C2 levels may be low in
some patients, which suggests activation of both classical and alternative pathways [39]. The C3 and CH50
return to normal within four to eight weeks after presentation.
Culture Because PSGN presents weeks after an antecedent GAS infection, only approximately 25
percent of patients will have either a positive throat or skin culture [7]. In patients with impetigo, there is an
increased likelihood of obtaining a positive skin culture [27].
Serology Elevated titers of antibodies to extracellular streptococcal products is evidence of a recent

GAS infection. (See "Group A streptococcus: Virulence factors and pathogenic mechanisms", section on
'Cytolysins'.)
The streptozyme test, which measures five different streptococcal antibodies, is positive in more than 95
percent of patients due to pharyngitis and approximately 80 percent of those with skin infections [35,40,41]. It
includes the following antibodies:
Anti-streptolysin (ASO)
Anti-hyaluronidase (AHase)
Anti-streptokinase (ASKase)
Anti-nicotinamide-adenine dinucleotidase (anti-NAD)
Anti-DNase B antibodies
These antibodies can also be measured individually. After a pharyngeal infection, the ASO, anti-DNase B,
anti-NAD, and AHase titers are commonly elevated. In comparison, only the anti-DNase B and AHase titers
are typically increased after a skin infection.
If only the ASO titer is used to screen for GAS infection, it may be falsely low or negative in patients with skin
infections [40]. It remains a useful test in patients with PSGN due to GAS pharyngitis but in some cases, the
rise in ASO titer may be blunted in patients with pharyngitis who have received antimicrobial therapy. (See
"Group A streptococcus: Virulence factors and pathogenic mechanisms", section on 'Streptolysin O'.)
DIAGNOSIS PSGN is usually diagnosed based upon clinical findings of acute nephritis and demonstration
of a recent group A beta-hemolytic streptococcal (GAS) infection.
The clinical findings of acute nephritis include hematuria with or without red blood cell casts, variable
degrees of proteinuria, edema, oliguria, and hypertension. (See 'Clinical manifestations' above.)
Documentation of a recent GAS infection includes either a positive throat or skin culture or serologic
tests (eg, anti-streptolysin [ASO] or streptozyme test). (See 'Serology' above.)
Although a low C3 and/or CH50 (total complement) level are consistent with a diagnosis of PSGN, these
complement components may also be decreased in other forms of glomerulonephritis, including
membranoproliferative glomerulonephritis. (See 'Differential diagnosis' below.)
A delay in the diagnosis of PSGN is more common in children who do not have a history of an antecedent
GAS infection and have microscopic hematuria. This was illustrated in a case series of 57 children with
PSGN who had a delay in diagnosis of greater than 24 hours [42]. In most of the patients, presenting
findings

were due to volume overload and included hypertension, edema, and pulmonary edema. The authors
concluded that acute nephritis needs to be considered in any child who presents with symptoms secondary to
volume overload and that a urinalysis should be obtained as an initial diagnostic test.
Renal biopsy is not performed in most patients to confirm the diagnosis of PSGN, since the resolution of
PSGN typically begins within one week of presentation. (See 'Renal biopsy' below and 'Indications for renal
biopsy' below.)
DIFFERENTIAL DIAGNOSIS The diagnosis of PSGN is generally straightforward in patients once the
diagnosis of acute nephritis is made, there is documentation of a recent group A beta-hemolytic streptococcal
(GAS) infection, and the nephritis begins to resolve within one or two weeks of presentation. However, if
there is progressive disease beyond two weeks, persistent hematuria or hypertension beyond four or six
weeks, or there is not adequate documentation of an antecedent GAS infection, the following causes of
glomerulonephritis (GN) need to be considered. A renal biopsy may be needed to differentiate PSGN from
these other disorders:
Membranoproliferative glomerulonephritis (MPGN) The presentation of MPGN may be

indistinguishable initially from PSGN. It typically presents with hematuria, hypertension, proteinuria, and
hypocomplementemia, which may follow an upper respiratory infection in some patients. However,
patients with MPGN continue to have persistent urinary abnormalities and hypocomplementemia beyond
four to six weeks and possibly a further elevation in serum creatinine. In contrast, patients with PSGN
typically have resolution of their disease and a return of normal C3 and CH50 levels. (See "Clinical
presentation, classification, and causes of membranoproliferative glomerulonephritis".)
IgA nephropathy Patients with IgA nephropathy often present after an upper respiratory infection,
similar to the presentation of patients with PSGN. Potential distinguishing features from PSGN include a
shorter time between the antecedent illness and hematuria (less than 5 versus more than 10 days in
PSGN) and a history of prior episodes of gross hematuria since recurrence is rare in PSGN. (See
"Differential diagnosis and evaluation of glomerular disease", section on 'Hematuria following upper
respiratory infection' and "Clinical presentation and diagnosis of IgA nephropathy".)
Secondary causes of glomerulonephritis Lupus nephritis and Henoch-Schnlein purpura (IgA

vasculitis) nephritis share similar features to PSGN. However, extrarenal manifestations of the underlying
systemic diseases and laboratory testing should differentiate them from PSGN. Measurement of serum
complement may also be helpful. Hypocomplementemia is not observed in patients with Henoch-
Schnlein purpura (IgA vasculitis) and the hypocomplementemia that occurs in lupus nephritis is, as
mentioned above, associated with reductions in both C3 and C4, whereas C4 levels are usually normal
in PSGN. (See "Renal manifestations of Henoch-Schnlein purpura (IgA vasculitis)" and "Diagnosis and
classification of renal disease in systemic lupus erythematosus" and 'Complement' above.)
Both hepatitis B and endocarditis-associated glomerulonephritis share common features with PSGN and
also will present with reductions in C3 and C4. (See "Renal disease associated with hepatitis B virus
infection" and "Renal disease in the setting of infective endocarditis or an infected ventriculoatrial
shunt".)
Postinfectious GN due to other microbial agents Acute nephritis due to viral and other bacterial agents
has been reported (table 1). The clinical presentation is similar to that of PSGN except that there is no
documentation of an antecedent GAS infection.
ACUTE MANAGEMENT
Supportive care There is no specific therapy for PSGN. Management is supportive and is focused on
treating the clinical manifestations of the disease, particularly complications due to volume overload. These
include hypertension and, less commonly, pulmonary edema. General measures include sodium and water

restriction and loop diuretics. (See "Evaluation and management of edema in children", section on 'General

treatment approach'.)
Loop diuretics generally provide a prompt diuresis with reduction of blood pressure and edema. In our
practice, intravenous furosemide is given at an initial dose of 1 mg/kg (maximum 40 mg).
Infrequently, patients have hypertensive encephalopathy due to severe hypertension. These patients should
be treated emergently to reduce their blood pressure. Oral nifedipine or parenteral nicardipine are effective,
while angiotensin-converting enzyme (ACE) inhibitors should be used with caution due to the risk of
hyperkalemia. (See "Management of hypertensive emergencies and urgencies in children", section on
'Approach'.)
Patients with PSGN have variable reductions in renal function, and some patients require dialysis during the
acute episode. The management of acute kidney injury in children, including indications for dialysis, is
discussed separately. (See "Prevention and management of acute kidney injury (acute renal failure) in
children", section on 'Management of acute kidney injury'.)
Patients with evidence of recurrent group A streptococcal (GAS) infection should be given a course of
antibiotic therapy. (See "Treatment and prevention of streptococcal tonsillopharyngitis", section on 'Recurrent
infection' and "Impetigo", section on 'Treatment'.)
Indications for referral Indications for referral to a center with expertise in treating children with
significant renal disease (eg, provide dialysis and perform renal biopsy) include:
Fluid overload that is unresponsive or slow to respond to supportive measures (fluid restriction and
diuretic therapy)
Refractory hypertension
Evidence of serious renal function compromise (elevated and rising serum creatinine)
Dialysis For patients with serious renal impairment, indications for dialysis include (see "Prevention
and management of acute kidney injury (acute renal failure) in children", section on 'Management of acute
kidney injury'):
Life-threatening fluid overload (pulmonary edema, heart failure, and hypertension) that is refractory to
medical therapy.
Hyperkalemia (serum or plasma potassium >6.5 mEq/L) unresponsive to medical therapy (see
"Management of hyperkalemia in children", section on 'Therapies removing potassium from the body').
Uremia defined as a BUN between 89 to 100 mg/dL.
Renal biopsy In the acute setting, because it is unusual for patients with PSGN to require dialysis, a
renal biopsy is performed in patients with significant renal impairment who require or are progressing towards
dialysis treatment to confirm the diagnosis of PSGN. Although there is no evidence that aggressive
immunosuppressive therapy has a beneficial effect in patients with rapidly progressive crescentic disease
[43], patients with more than 30 percent crescents on renal biopsy are often treated with methylprednisolone
pulses. (See "Overview of the classification and treatment of rapidly progressive (crescentic)
glomerulonephritis", section on 'Treatment'.)
COURSE AND FOLLOW-UP Resolution of the clinical manifestations of PSGN is generally quite rapid,
assuming concurrent resolution of the infection. A diuresis typically begins within one week, and the serum
creatinine returns to the previous baseline by three to four weeks [8,44].
The urinary abnormalities disappear at differing rates. Hematuria usually resolves within three to six months.
Proteinuria also falls during recovery, but at a much slower rate. A mild increase in protein excretion is still

present in 15 percent at 3 years, and 2 percent at 7 to 10 years [45].
In severe cases with nephrotic range proteinuria (defined as 1000 mg/m2 per day or 40 mg/m2 per hour),
this degree of proteinuria may persist for six months or more, long after the hematuria has disappeared
[23,46]. Patients first seen at this late stage are often thought to have one of the causes of the idiopathic
nephrotic syndrome (eg, membranous nephropathy, focal segmental glomerulosclerosis, or minimal change
disease).
Indications for renal biopsy A biopsy is usually performed in patients in whom other glomerular
disorders are being considered because their disease courses deviates from that of PSGN or they present
late without a clear history of prior streptococcal infection. (See 'Differential diagnosis' above and 'Course and
follow-up' above.)
Persistently low C3 levels beyond six weeks are suggestive of a diagnosis of membranoproliferative
glomerulonephritis as C3 levels typically normalize in patients with PSGN by this timeframe. (See
"Clinical presentation, classification, and causes of membranoproliferative glomerulonephritis" and "C3
glomerulopathies: Dense deposit disease and C3 glomerulonephritis".)
Recurrent episodes of hematuria are suggestive of IgA nephropathy and are rare in PSGN.
A persistent or progressive increase in serum creatinine is uncharacteristic of PSGN, but there are
occasional patients whose renal function does not fully recover.
Correlation with histologic recovery The histologic course parallels the improvements seen clinically.
There is a marked reduction in the number of inflammatory cells in the glomeruli and the number of immune
deposits seen on electron microscopy as the clinical manifestations resolve [26,47].
The prolonged resolution of proteinuria compared with the more rapid return of renal function and remission
of hematuria probably reflects the slower rate of clearance of subepithelial compared with subendothelial
immune complexes.
Subendothelial immune complexes are rapidly cleared by the inflammatory cells from the systemic
circulation, thereby accounting for the resolution of hematuria and renal insufficiency [26]. They may not
be seen on renal biopsy unless performed early in the course.
Subepithelial deposits are separated from circulating inflammatory cells by the glomerular basement
membrane, thereby limiting their rate of removal [26,47]. In general, the degree of proteinuria correlates
with the number of subepithelial deposits [23].
Recurrence Recurrent episodes of PSGN are rare [27,29,48,49]. This may be due to the long-term
persistence of antibodies to nephritis-associated streptococcal antigens [50]. (See 'Nephritogenic antigens'
above.)
PROGNOSIS Most patients, particularly children, have an excellent outcome [2,8,25,45]. This is true even
in patients who present with acute renal failure and may have crescents on the initial renal biopsy [43,44,51].
A review of three case series of 229 children with PSGN found that approximately 20 percent had an
abnormal urinalysis (proteinuria and/or hematuria), but almost all (92 to 99 percent) had normal or only
modestly reduced renal function 5 to 18 years after presentation [2].
However, the long-term prognosis of PSGN is not always benign [52]. Some patients, particularly adults,
develop hypertension, recurrent proteinuria (with a relatively normal urine sediment), and renal insufficiency
as long as 10 to 40 years after the initial illness [53-56]. A study from Australia involved 200 Aboriginal
children who had had at least one episode of PSGN, with 27 having had multiple episodes. In this cohort, all
PSGN episodes were associated with group A streptococcal (GAS) skin infections, often related to scabies.
Five years or later, these patients were three to four times more likely to have significant albuminuria
compared with people without a previous history of PSGN [57].
These late renal complications are associated with glomerulosclerosis on renal biopsy, which is thought to be
hemodynamically mediated. According to this hypothesis, some glomeruli are irreversibly damaged during
the acute episode and compensatory hyperfiltration in the remaining glomeruli maintains a relatively normal
glomerular filtration rate (GFR). However, this adaptive response results in increases in glomerular pressure
and size, both of which may then contribute to nonimmunologic glomerular injury and progressive renal
dysfunction. It is possible that, in those patients who develop glomerulosclerosis, renal damage can be
prevented or ameliorated by antihypertensive therapy (preferentially with an angiotensin-converting enzyme
[ACE] inhibitor). (See "Secondary factors and progression of chronic kidney disease".)
An alternate explanation for the late development of renal failure in patients diagnosed initially with PSGN is
that some patients may actually have membranoproliferative glomerulonephritis [25]. (See 'Differential
diagnosis' above.)
SUMMARY AND RECOMMENDATIONS
Poststreptococcal glomerular nephritis (PSGN) is the most common cause of acute nephritis worldwide.
It primarily occurs in the developing world. The risk of PSGN is greatest in children between 5 and 12
years of age, and in older adults greater than 60 years of age. (See 'Epidemiology' above.)
PSGN is caused by glomerular immune complex disease induced by specific nephritogenic strains of
group A beta-hemolytic streptococcus (GAS). The two leading candidates for nephritogenic antigens are
nephritis-associated plasmin receptor and streptococcal pyogenic exotoxin B. (See 'Pathogenesis'
above.)
The characteristic pathologic features of PSGN are demonstrated by electron microscopy (dome-shaped
subepithelial deposits) (picture 4) and immunofluorescence (deposition of immunoglobulin G [IgG] and
C3 in a diffuse granular pattern in the mesangium and glomerular capillary walls) (picture 3). The light
microscopic findings of cellular infiltration and glomerular proliferation are nonspecific. (See 'Pathology'
above.)
Although, the most common clinical findings include edema, gross hematuria, and hypertension, the
presentation of PSGN varies from asymptomatic, microscopic hematuria to the full-blown acute nephritic
syndrome (gross hematuria, proteinuria, edema, hypertension, and acute kidney injury). (See 'Clinical
manifestations' above.)
Laboratory findings include an abnormal urinalysis (dysmorphic red blood cells, varying degrees of
proteinuria, red blood cell casts, and pyuria), positive serology for antibodies to streptococcal antigens,
and hypocomplementemia. (See 'Laboratory findings' above.)
PSGN is typically diagnosed based upon the findings of acute nephritis (eg, hematuria with or without
red blood cell cases and proteinuria) and demonstration of a recent GAS infection (eg, positive throat or
skin culture or serologic tests [anti-streptolysin [ASO] or streptozyme test]). (See 'Diagnosis' above.)
Although several glomerulonephritides (eg, membranoproliferative glomerulonephritis and

immunoglobulin A [IgA] nephropathy) have similar presentations to PSGN, specific clinical differences
usually can differentiate among them. In cases where the diagnosis is uncertain, a renal biopsy may be
needed to identify the specific renal disease. (See 'Differential diagnosis' above and 'Indications for renal
biopsy' above.)
There is no specific therapy to treat PSGN. Management is supportive and is focused upon treating the
volume overload that causes the clinical complications of PSGN. These general measures include
sodium and water restriction, and diuretic therapy.
In patients with acute renal failure, dialysis may be required. The indications for dialysis are
discussed separately. (See "Prevention and management of acute kidney injury (acute renalfailure)

in children", section on 'Management of acute kidney injury'.)
In patients with hypertension, we suggest administration of lasix to provide a prompt diuresis and a
reduction of blood pressure (Grade 2C). Infrequently, patients may have hypertensive
encephalopathy due to severe hypertension and require emergent therapy to reduce their blood
pressure. (See 'Acute management' above and "Management of hypertensive emergencies and
urgencies in children", section on 'Approach'.)
Most patients, particularly children, have complete clinical recovery, and resolution of their disease
process begins within the first two weeks. However, there is a small subset of patients who have late
renal complications (ie, hypertension, increasing proteinuria, and renal insufficiency). (See 'Course and
follow-up' above and 'Prognosis' above.)
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Topic 6118 Version 23.0

GRAPHICS
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.
Courtesy of Helmut Rennke, MD.
Graphic 76739 Version 4.0
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.
Courtesy of Helmut G Rennke, MD.
Postinfectious glomerulonephritis
Low-power light micrograph showing diffuse, proliferative glomerulonephritis as

may be seen in postinfectious glomerulonephritis. The glomeruli are so
hypercellular (arrows) that open capillary lumens cannot be seen, and the
glomeruli may be hard to distinguish from the surrounding interstitium.
Poststrep GN high power
Acute postinfectious glomerulonephritis. The glomeruli show global intracapillary

hypercellularity with large numbers of polymorphonuclear leukocytes in the
glomerular capillary lumina (hematoxylin and eosin stain, x400). (Courtesy of
Peter Degrell, University of Pcs Faculty of Medicine, Nephrological Center, Pcs,
Hungary.)
Reproduced with permission from: Knoers NV, Monnens LA. Nephrogenic diabetes
insipidus. In: Pediatric Nephrology, 5th ed, Avner ED, Harmon WE, Niaudet P (Eds),
Lippincott Williams & Wilkins, Philadelphia 2004. Copyright 2004 Nine V.A.M.
Knoers.
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.
Phase-contrast micrograph showing dysmorphic red

cells in urine sediment
Phase-contrast microscopy showing dysmorphic red cells in a patient with

glomerular bleeding. Acanthocytes can be recognized as ring forms with vesicle-
shaped protrusions (arrows).
Courtesy of Hans Khler, MD.
Scanning electron micrograph showing dysmorphic red

cells in urine sediment
Scanning microscopy showing dysmorphic red cells in a patient with glomerular

bleeding. Acanthocytes can be recognized as ring forms with vesicle-shaped
protrusions (arrows).
Courtesy of Hans Khler, MD.
Photomicrograph of urine sediment with a red cell cast
Image
Urine sediment showing free red cells and a red cell cast that is tightly packed
with red cells. It is more common for red cell casts to have fewer red cells
trapped within a hyaline or granular cast. Red cell casts are virtually diagnostic
of glomerulonephritis or vasculitis.
Courtesy of Harvard Medical School.
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.
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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Author: Patrick Niaudet, MD

INTRODUCTION Poststreptococcal glomerulonephritis (PSGN) is caused by prior infection with specific

PATHOGENESIS PSGN appears to be caused by glomerular immune complex disease induced by

Deposition of circulating immune complexes with streptococcal antigenic components.

Rheumatic factor are detected in two-thirds of patients with PSGN.

Nephritis-associated plasmin receptor (NAPlr), a glycolytic enzyme, which has glyceraldehyde-3-

Immunofluorescence microscopy Immunofluorescence (IF) microscopy reveals a characteristic pattern

Serology Elevated titers of antibodies to extracellular streptococcal products is evidence of a recent

Membranoproliferative glomerulonephritis (MPGN) The presentation of MPGN may be

Secondary causes of glomerulonephritis Lupus nephritis and Henoch-Schnlein purpura (IgA

Uremia defined as a BUN between 89 to 100 mg/dL.

SUMMARY AND RECOMMENDATIONS

Although several glomerulonephritides (eg, membranoproliferative glomerulonephritis and

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55. Baldwin DS. Chronic glomerulonephritis: nonimmunologic mechanisms of progressive glomerular

Topic 6118 Version 23.0

Electron micrograph of postinfectious glomerulonephritis

Electron micrograph shows subepithelial deposits (D) with a semilunar, hump-

Courtesy of Helmut Rennke, MD.

Graphic 76739 Version 4.0

Electron micrograph of a normal glomerulus

Electron micrograph of a normal glomerular capillary loop showing the

Courtesy of Helmut G Rennke, MD.

Graphic 50018 Version 7.0

Low-power light micrograph showing diffuse, proliferative glomerulonephritis as

Courtesy of Helmut Rennke, MD.

Graphic 80304 Version 2.0

Poststrep GN high power

Acute postinfectious glomerulonephritis. The glomeruli show global intracapillary

Graphic 51022 Version 3.0

Immunofluorescence microscopy shows granular deposition of complement in

Courtesy of Helmut Rennke, MD.

Graphic 56846 Version 2.0

Phase-contrast micrograph showing dysmorphic red

Phase-contrast microscopy showing dysmorphic red cells in a patient with

Courtesy of Hans Khler, MD.

Graphic 79440 Version 4.0

Scanning electron micrograph showing dysmorphic red

Scanning microscopy showing dysmorphic red cells in a patient with glomerular

Courtesy of Hans Khler, MD.

Graphic 62064 Version 3.0

Photomicrograph of urine sediment with a red cell cast

Courtesy of Harvard Medical School.

Graphic 55778 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)

Graphic 76710 Version 3.0

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