generally normal, distinguishing HUS from sepsis and disseminated
intravascular coagulation. A Coombs test will be negative. A stool culture
may help identify the causative organism but will not alter medical
management of AKI.
The severity of the renal involvement in typical HUS varies widely and is
not related to the degree of anemia present. AKI may be mild and selflimited, associated with microscopic hematuria, mild proteinuria, and
preserved renal function. When renal microangiopathy is severe, fulminant
oligoanuric renal failure may ensue and necessitate RRT.
Management. Early IV hydration in the setting of known STEC
enterocolitis is important. Fluid administration, especially early in the
course of illness when diarrhea may be present without signs of HUS, is
associated with a decreased risk of requiring RRT, shorter hospital stays,
and decreased risk of long-term sequelae. Supportive care is the mainstay of
therapy for typical HUS, once developed. If intravascular volume depletion
is present due to gastrointestinal losses and poor intake, fluid resuscitation
with isotonic saline should be provided with repeated assessment of volume
status in an effort to decrease the compounding effects of prerenal AKI.
Once the intravascular volume status has been restored, further fluid
management should be guided by renal function and urine flow. If oliguria
is present, a trial of furosemide (0.5 to 1 mg/kg/dose) may be provided to
establish urine flow, although patients may require doses much larger than
typical (up to 5 mg/kg/dose). If oliguria persists, fluids should be provided
at a rate to ensure adequate intravascular volume but avoid volume excess.
Both IV and oral intake should match the total of measurable output (urine
and gastrointestinal losses) and insensible water losses, estimated at 300 to
400 mL/m2/day. Frequent monitoring of fluid balance, weight, and vital
signs is essential. Hypertension may be managed with calcium channel
blockers.
Anemia associated with typical HUS may be severe. Packed red blood
cell transfusions should be provided for symptomatic anemia or robust
hemolysis with a hemoglobin <6 to 7 mg/dL. Transfusions should occur

slowly given the concern for fluid balance issues. If the patient is oliguric, it
may need to be performed while on dialysis to avoid volume excess and
hyperkalemia. Due to microangiopathy, transfused platelets will be quickly
consumed and not lead to a sustained increase in the platelet count. Platelet


transfusion is only indicated in patients with active bleeding or when an
invasive procedure is intended.
Up to 50% of children with typical HUS will require RRT. Dialysis is
also indicated to safely provide blood products and nutritional support in
the setting of persistent oligoanuria. The modality of dialysis depends on
the expertise of the center. However, if there are severe abdominal
complications requiring surgical intervention, hemodialysis will be
necessary as peritoneal dialysis will be contraindicated.

Postinfectious Glomerulonephritis
Goals of Treatment
The goals of treatment for postinfectious glomerulonephritis are supportive
in nature. The consequences of fluid retention such as pulmonary edema
and hypertension should be managed, as necessary. AKI and its
complications may necessitate medical intervention such as RRT in severe
cases. Children with evidence of active underlying infections should be
treated appropriately.
CLINICAL PEARLS AND PITFALLS
Clinical presentation of nephritis includes hematuria, edema, and
hypertension.
Postinfectious glomerulonephritis most often occurs after an
infection with group A streptococci.
Care is supportive, including management of fluid balance and
blood pressure, and most children recover fully.

Clinical Considerations
Clinical recognition. Postinfectious glomerulonephritis is the leading cause
of glomerulonephritis in children worldwide and has been associated with a
multitude of bacteria, viruses, and parasites. Historically, nephritogenic
strains of group A β-hemolytic streptococci have been the most frequently
implicated organisms, often after a proceeding pharyngitis or cellulitis.
However, in recent years nonstreptococcal organisms have emerged as the
leading cause of postinfectious glomerulonephritis in high-income


countries. Many organisms including Staphylococcus sp ., Pneumococcus,
Salmonella typhi, Klebsella pneumoniae, and E. coli may be causative.
In regards to streptococcal-related nephritis, the latent period from
infection to acute poststreptococcal glomerulonephritis (APSGN) is
generally 1 to 3 weeks after pharyngitis and 3 to 6 weeks with skin
infections. It most often affects children aged 4 to 14 years old, and rarely
occurs in children less than 2 years old. Males are more often affected. In
recent decades, the prevalence of APSGN has declined in most
industrialized nations, although it persists at high rates in some developing
countries.
The clinical presentation of APSGN may vary from asymptomatic
microscopic hematuria to an abrupt onset of nephritic syndrome.
Subclinical APSGN is four to five times more common than an acute
clinical presentation, which can be associated with gross hematuria,
proteinuria, oliguria, edema, and hypertension. Hypertension can be severe
and evolve into hypertensive emergency, which typically affects the CNS in
children. Symptoms include headache, seizure, and encephalopathy.
Clinical assessment. A detailed history and physical examination should
be completed when there is a suspicion of APSGN. The color and quantity
of urine output should be assessed by history. A history of a preceding

streptococcal infection may be present, although the infection may not have
been identified at the time. The physical examination should assess for the
consequences of APSGN. The patient should be evaluated for signs of fluid
overload including hypertension, and the signs and symptoms of
hypertensive crisis should be addressed.
Laboratory studies during a typical episode of APSGN reflect a nephritis
with activation of the alternative complement pathway. Serum studies may
demonstrate reduced renal function. Associated electrolyte abnormalities
include hyponatremia, reflecting an inability to excrete water, and
hyperkalemia. The majority of patients have a low C3 complement, and a
normal C4 complement. The C3 level normalizes in 6 to 8 weeks. If the C3
remains depressed after 3 months or the C4 is low, diagnostic
considerations include chronic forms of glomerulonephritis, including
membranoproliferative glomerulonephritis (MPGN) and lupus nephritis. If
the complement levels are normal at presentation, APSGN is less likely, and
IgA nephropathy would be a consideration.


Serologic testing to document recent streptococcal infection is helpful but
does not prove causation, as a significant number of children are
asymptomatic carriers. Serologic tests available include titers for
antistreptolysin
O
(ASO),
antihyaluronidase,
antistreptokinase,
antinicotinamide-adenine dinucleotidase, and anti-DNAse B. ASO may be
negative in the setting of streptococcal cellulitis, and it is important to note
that antibiotic therapy may blunt the increase in antibody titers.
The urine sediment will demonstrate glomerular erythrocytes and

leukocytes, and may contain red cell casts. Proteinuria is not uncommon,
though not typically in the nephrotic range.
Renal biopsy is generally not indicated for the diagnosis of APSGN. It
may be considered if the clinical picture does not clearly support a
diagnosis of APSGN, if renal function does not recover in an expected
fashion, or if C3 levels remain persistently low.
Clinical management. Therapy for APSGN is largely supportive although
antibiotics should be initiated if active infection is still present. Given the
underlying glomerular inflammation and generally intact tubular function,
there is a propensity for salt and water retention leading to edema and
increased blood pressure. Therefore, weight should be measured daily and
blood pressure checked regularly during the early acute illness. Children
with hypertension or decreased renal function should be considered for
admission. If edema or hypertension is present, salt and fluid restriction
should be initiated and diuretic therapy considered. Furosemide can be
provided at doses of 0.5 to 1 mg/kg once to four times daily to optimize
fluid balance. If the child is hypertensive, short- or long-acting calcium
channel blockers can be initiated while awaiting recovery. If the blood
pressure is significantly elevated, IV hydralazine 0.1 mg/kg can be given
every 4 to 6 hours with appropriate dose adjustment until other supportive
measures are effective. If a child demonstrates persistent hypertension and
proteinuria and if renal function has been stable, ACE inhibitors can be
considered with close monitoring of serum creatinine and potassium.
The prognosis for complete recovery from the initial episode of APSGN
is good, even for those who presented with renal insufficiency or
hypertension. Generally, the clinical symptoms of APSGN begin to improve
after 1 to 2 weeks. If reduced renal function and edema are evident at
presentation, renal function begins to normalize and diuresis ensues within