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Hematuria
Hematuria is defined as the presence of at least 5 red blood cells (RBCs)
per microliter of urine and occurs with a prevalence of 0.5-2.0% among
school-age children.
The presence of 10-50 RBCs/μL may suggest underlying pathology, but
significant hematuria is generally considered as >50 RBCs/μL.
Common Causes OF Grosse Hematuria
1. UTI
2. meatal stenosis
3. perinatal irritation
4. trauma
5. stone
6. coagulopathy
7. tumor
8. glomeruler diseases(IgA nephropathy, post infectious GN, HSP,
SLE
Immunoglobulin A Nephropathy (Berger Nephropathy)
IgA nephropathy is the most common chronic glomerular disease in
children. It is characterized by a predominance of IgA within mesangial
glomerular deposits in the absence of systemic disease.
Clinical And Laboratory Manifestations
IgA nephropathy is seen more often in male than in female patients.
A majority of children with IgA nephropathy present with gross
hematuria,
Gross hematuria often occurs within 1-2 days of onset of an upper
respiratory or gastrointestinal infection, in contrast to the longer latency
period observed in acute PSGN, and may be associated with loin pain.
Proteinuria is often <1000 mg/24 hr in patients with asymptomatic
microscopic hematuria.
Mild to moderate hypertension is most often seen in patients with
nephritic or nephrotic syndrome
Normal serum levels of C3 in IgA nephropathy help to distinguish this
disorder from PSGN.
Serum IgA levels have no diagnostic value because they are elevated in
only 15% of pediatric patients.
Prognosis
Although IgA nephropathy does not lead to significant kidney damage
in most children, progressive disease develops in 20-30% of patients
15-20 yr after disease onset.
Poor prognostic
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Persisten hypertension, diminished renal function, and significant
increasing, or prolonged proteinuria.
Treatment
The primary treatment of IgA nephropathy is appropriate blood
pressure control and management of significant proteinuria.
Angiotensin-converting enzyme inhibitors and angiotensin II receptor
antagonists are effective in reducing proteinuria
corticosteroids
Tonsillectomy
kidney transplantation.
Alport Syndrome
AS, or hereditary nephritis, is a genetically heterogeneous disease
caused by mutations in the genes coding for type IV collagen, a major
component of basement membranes.
Genetics
Approximately 85% of patients have X-linked inheritance
An autosomal recessive 10%
An autosomal dominant 5% of cases.
Clinical Manifestations
All patients with AS have asymptomatic microscopic hematuria, which
may be intermittent in girls and younger boys.
Single or recurrent episodes of gross hematuria commonly occurring 1-2
days after an upper respiratory infection are seen in approximately 50%
of patients.
Progressive proteinuria, often exceeding 1 g/24 hr, is common by the 2nd
decade of life and can be severe enough to cause nephrotic syndrome.
Bilateral sensorineural hearing loss (which is never congenital),develops
in 90% of hemizygous males with X-linked AS
Ocular abnormalities, which occur in 30-40% of patients with X-inked
AS include anterior lenticonus (extrusion of the central portion of the lens
into the anterior chamber) is pathognomonic
Diagnosis
A combination of careful family history, a screening urinalysis of
1stdegree relatives, an audiogram, and an ophthalmologic examination
are critical in making the diagnosis of AS.
Prognosis And Treatment
The risk of progressive renal dysfunction leading to end-stage renal
disease (ESRD) is highest among hemizygotes and autosomal recessive
homozygotes.
ESRD occurs before age 30 yr in approximately 75%
No specific therapy is available to treat AS, althoug angiotensin-2
receptor inhibitors) can slow the rate of progression.
Careful management of renal failure complications such as hypertension,
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anemia, and electrolyte imbalance is critical.
Patients with ESRD are treated with dialysis and kidney transplantation
Acute poststreptococcal glomerulonephritis (APSGN)
Is a classic example of the acute nephritic syndrome characterized by
the sudden onset of gross hematuria, edema, hypertension, and renal
insufficiency. It is one of the most common glomerular causes of gross
hematuria in children and is a major cause of morbidity in group A
β-hemolytic streptococcal infections.
Etiology and Epidemiology
Poststreptococcal GN commonly follows streptococcal pharyngitis
(serotype 12) during cold-weather months and streptococcal
skin infections or pyoderma (serotype 49) during warm-weather months.
Pathology
Glomeruli appear enlarged and relatively bloodless and show diffuse
mesangial cell proliferation, with an increase in mesangial matrix
Pathogenesis
circulating antibodies elicited by streptococcal antigens react with normal
glomerular antigens
Clinical Manifestations
Poststreptococcal GN is most common in children ages 5-12 yr and
uncommon before the age of 3 yr.
The typical patient develops an acute nephritic syndrome 1-2 wk after an
antecedent streptococcal pharyngitis or 3-6 wk after a streptococcal
pyoderma.
The severity of kidney involvement varies from asymptomatic
microscopic hematuria with normal renal function to gross hematuria
with acute renal failure.
Depending on the severity of renal involvement, patients can develop
various degrees of edema(typically results from salt and water retention
and is common), hypertension, oliguria, encephalopathy and/or
pulmonary edema and heart failure secondary to hypertension or
hypervolemia.
nephrotic syndrome develops in a minority (<5%) of childhood cases.
Nonspecific symptoms such as malaise, lethargy, abdominal pain, or
flank pain are common.
The acute phase generally resolves within 6-8 wk. Although urinary
protein excretion and hypertension usually normalize by 4-6 wk after
onset, persistent microscopic hematuria can persist for 1-2 yr after the
initial presentation.
Diagnosis
Urinalysis demonstrates red blood cells, often in association with red
blood cell casts, proteinuria, and polymorphonuclear leukocytes.
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mild normochromic anemia may be present from hemodilution and
low-grade hemolysis.
Blood urea and serum creatinine either normal or increase.
The serum C3 level is significantly reduced and returns to normal 6-8 wk
after onset.
Confirmation of the diagnosis requires clear evidence of a prior
streptococcal infection.
A rising antibody titer to streptococcal antigen(s) confirms a recent
streptococcal infection.
The antistreptolysin O titer is commonly elevated after a pharyngeal
infection but rarely increases after streptococcal skin infections.
The best single antibody titer to document cutaneous streptococcal
infection is the antideoxyribonuclease B level.
A positive throat culture report might support the diagnosis or might
represent the carrier state.
Magnetic resonance imaging of the brain is indicated in patients
with severe neurologic symptoms and can demonstrate posterior
reversible encephalopathy syndrome in the parietooccipital areas on
T2-weighted images.
Chest x-ray is indicated in those with signs of heart failure or respiratory
distress, or physical exam findings of a heart gallop, decreased breath
sounds, rales, or hypoxemia.
The clinical diagnosis of poststreptococcal GN is quite likely in a
child presenting with acute nephritic syndrome, low C3 level, and
evidence streptococcal infection.
Differential Diagnoses
IgA, SLE, HSP, endocarditis, membranoproliferative GN, and an acute
exacerbation of chronic GN.
Renal biopsy should be considered only in the presence of
1. acute renal failure
2. nephrotic syndrome
3. absence of evidence of streptococcal infection
4. normal complement C3, C4 levels.
5. hematuria and proteinuria, diminished renal function, and/or a low
C3 level persist more than 2 mo after onset.
Acute postinfectious GN can also follow other infections with coagulase-
positive
and
coagulase-negative
staphylococci,
Streptococcus
pneumoniae, Gram-negative bacteria, certain fungal, rickettsial,
protozoan, parasitic, or viral diseases. Among the latter, influenza and
parvovirus infections are particularly notable.
Complications
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Acute complications result from hypertension and acute renal
dysfunction.
Hypertension is seen in 60%, and hypertensive encephalopathy in 10% of
cases
Other potential complications include heart failure, hyperkalemia,
hyperphosphatemia, hypocalcemia, acidosis, and seizures
Prevention
1. Early systemic antibiotic therapy for streptococcal throat and skin
infections does not eliminate the risk of GN.
2. Family members of patients with acute GN, especially young
children, should be consideredat risk and be cultured for group A
β-hemolytic streptococci and treated if positive.
3. Family pets, particularly dogs, have also been reported as carriers.
Treatment
1. Management is directed at treating the acute effects of renal
insufficiency and hypertension.
2. Although a 10 day course of systemic antibiotic therapy with
penicillin is recommended to limit the spread of the nephritogenic
organisms, antibiotic therapy does not affect the natural history of
APSGN.
3. Sodium restriction, diuresis (usually with intravenous furosemide),
and pharmacotherapy with calcium channel antagonists, vasodilators,
or ACEI are standard therapies used to treat hypertension.
Prognosis
Complete recovery occurs in >95% of children with APSGN.
Recurrences are extremely rare.
Hemolytic-uremic syndrome (HUS)
is a common cause of community acquired acute kidney injury in young
children. It is characterized by the triad of microangiopathic hemolytic
anemia, thrombocytopenia, and renal insufficiency.
Etiology
The various etiologies
infection-induced, genetic, medication-induced, and associated with
systemic diseases
The most common form of HUS is caused by toxin-producing
Escherichia coli that causes prodromal acute enteritis and is commonly
termed diarrhea-associated HUS.
Pathology
Early glomerular changes include thickening of the capillary walls caused
by swelling of endothelial cells and accumulation of fibrillar material
between endothelial cells and the underlying basement membrane,
causing narrowing of the capillary lumens.
Pathogenesis
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Microvascular injury with endothelial cell damage is characteristic of
all forms of HUS.
In each form of HUS, capillary and arteriolar endothelial injury in
the kidney leads to localized thrombosis, particularly in glomeruli,
causing a direct decrease in glomerular filtration. Progressive platelet
aggregation in the areas of microvascular injury results in consumptive
thrombocytopenia. Microangiopathic hemolytic anemia results from
mechanical damage to red blood cells as they pass through the damaged
and thrombotic microvasculature.
Clinical Manifestations
HUS is most common in preschool and school-age children, but it can
occur in adolescents and adults.
In HUS caused by toxigenic E. coli, onset of HUS occurs a few days
after onset of gastroenteritis with fever, vomiting, abdominal pain, and
diarrhea.
The diarrhea is often bloody, but not necessarily so.
the sudden onset of pallor, irritability, weakness, and lethargy heralds the
onset of HUS. Oliguria can be present in early stages but may be masked
by ongoing diarrhea, because the prodromal enteritis often overlaps
the onset of HUS, particularly with ingestion of large doses of toxin.
Thus, patients with HUS can present with either significant dehydration
or volume overload.
HUS can be relatively mild, or can progress to a severe and fatal
multisystem disease.
Leukocytosis, severe prodromal enteritis, and hyponatremia,
Patients with HUS who appear mildly affected at presentation can
rapidly develop severe, multisystem, life-threatening complications.
Renal insufficiency can be mild but also can rapidly evolve into severe
oliguric or anuric renal failure.
The combination of rapidly developing renal failure and severe hemolysis
can result in life-threatening hyperkalemia.
Volume overload, hypertension, and severe anemia can all develop soon
after onset of HUS, and together can precipitate heart failure.
The majority of patients with HUS have some central nervous system
(CNS) involvement. Most have mild manifestations, with significant
irritability, lethargy, or nonspecific encephalopathic features. Severe
CNS involvement occurs in ≤20% of cases.
Seizures and significant encephalopathy are the most common
manifestations in those with severe CNS involvement, resulting from
focal ischemia secondary to microvascular CNS thrombosis.
Patients can develop petechiae, but significant or severe bleeding is rare
despite very low platelet counts.
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Diagnosis
The diagnosis is made by the combination of
1. microangiopathic hemolytic anemia with schistocytes (the anemia
can be mild at presentation, but rapidly progresses)
2. thrombocytopenia (Thrombocytopenia is an invariable finding in
the acute phase, with platelet counts usually 20,000-100,000/mm3 )
3. some degree of kidney involvement(vary from mild elevations in
serum blood urea nitrogen and creatinine to acute anuric kidney
failure)
Differential Diagnoses
SLE, malignant hypertension, and bilateral renal vein thrombosis
Prognosis
The mortality for diarrhea-associated HUS is <5% in most major medical
centers.
Up to half of patients may require dialysis support during the acute
phase of the disease.
Most recover renal function completely, but of surviving patients, 5%
remain dependent on dialysis
up to 30%are left with some degree of chronic renal insufficiency. The
prognosis
for HUS not associated with diarrhea, and the familial, genetic forms of
HUS are have a poor prognosis
Treatment
Supportive care
includes careful management of fluid and electrolytes, including
prompt correction of volume deficit, control of hypertension, and early
institution of dialysis if the patient becomes significantly oliguric or
anuric, particularly with hyperkalemia.
Red cell transfusions are usually required as hemolysis can be brisk and
recurrent until the active phase of the disease has resolved.
Despite low platelet counts, serious bleeding is very rare in patients
with HUS.
Anticoagulation,
antiplatelet,
and
fibrinolytic
therapies
are
specifically contraindicated because they increase the risk of serious
hemorrhage.
Antibiotic therapy to clear enteric toxigenic organisms (STEC) can
result in increased toxin release, potentially exacerbating the disease, and
therefore is not recommended.
Plasma infusion or plasmapheresis has been proposed for patients
suffering severe manifestations of HUS with serious CNS involvement.