Hematuria is a common clinical presentation of different conditions in children. Etiology of microscopic and gross hematuria is different. Detailed history, physical examination and focused investigations help identify the cause of hematuria. Management and prognosis are determined by the etiology of hematuria. In this article, etiology, pathophysiology, clinical features, diagnosis, differential diagnosis, and management of pediatric hematuria are described.

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Image: “The Test Urine Container Urine Inflammation” by frolicsomepl. License: Public Domain


Definition

The presence of > 5 red blood cells (RBCs)/hpf on microscopic examination of centrifuged urine is called microscopic hematuria. A diagnosis usually requires the demonstration of > 5 RBCs/hpf in 3 consecutive urine specimens obtained 1 week apart. Hematuria that is visible to the naked eye is called macroscopic or gross hematuria.

Epidemiology of Hematuria

Prevalence of hematuria among school-aged children is 0.5–2 %. Microscopic hematuria is more common than macroscopic hematuria.

Etiology of Hematuria

Hematuria from the upper urinary tract (glomeruli, convoluted tubules, collecting tubules, interstitium):

Hematuria from the lower urinary tract (pelvocalyceal system, ureter, urinary bladder, urethra):

  • Urolithiasis
  • Hypercalciuria (hyperparathyroidism, vitamin D excess, prolonged immobilization, idiopathic hypercalciuria)
  • Trauma (including child abuse)
  • Tumors
  • Inflammation (cystitis, urethritis)
  • Structural abnormalities

Non-renal causes of hematuria

  • High fever
  • Following heavy exercise
  • Menstruation
  • Recent instrumentation such as catheterization

Common causes of gross hematuria in children

  • Urinary tract infection (bacterial UTI – the most common cause of gross hematuria in children)
  • Urolithiasis
  • Meatal stenosis
  • Trauma to urinary tract
  • Tumors of urinary tract
  • Hypercalciuria
  • Coagulopathies
  • Glomerular causes: PSGN, HSP nephritis, IgA nephropathy, Alport syndrome, thin GBM disease, SLE nephritis

Common causes of asymptomatic isolated microscopic hematuria in children

  • Benign familial hematuria (thin GBM disease)
  • Idiopathic hypercalciuria
  • IgA nephropathy
  • Sickle cell trait or anemia
  • Following renal transplant
  • Idiopathic

Pathophysiology of Hematuria

The origin of hematuria may be traced back to the kidneys (glomeruli, convoluted tubules, collecting tubules, interstitium) or to the urinary tract, i.e. collecting system, ureter, urinary bladder, and urethra.

When RBCs are of glomerular origin, they enter the capillary lumen after crossing the glomerular endothelial-epithelial barrier; hence, glomerular hematuria is accompanied by deformed RBCs (acanthocytes), RBC casts, and proteinuria. The presence of leukocytes in urine and renal tubular epithelial casts suggests the hematuria originating within convoluted tubules or collecting tubules.

Possible explanations for hematuria in hypercalciuria are irritation of uroepithelium by microcalculi and microscopic nephrocalcinosis.

Note: Non-renal conditions like high fever and heavy physical exercise can produce transient hematuria by altered renal hemodynamics.
glomerulonephritis

Image: by Lecturio

Chronic (no casts)
Primary Secondary
  • MPGN
  • Membranous nephropathy
  • Focal glomerulosclerosis
  • Mesangial proliferative nephritis
Same as acute secondary causes:

  • HSP
  • SLE
    Polyarteritis Nodosa
  • Hemolytic uremic syndrome (HUS)
  • Subacute endocarditis
  • Goodpasture syndrome
Acute (RBS Casts)
Primary Secondary
  • PSGN
  • Infectious GN
  • IgA nephropathy (Berger´s disease)
  • MPGN
  • HSP
  • SLE
  • Polyarteritis Nodosa
  • Hemolytic uremic syndrome (HUS)
  • Subacute endocarditis
  • Goodpasture syndrome

Symptoms of Hematuria

  • Hematuria of the upper urinary tract origin: brown, cola, or tea-colored urine or burgundy urine
  • Hematuria of the lower urinary tract origin: bright red or pink colored urine
  • Hematuria of the lower urinary tract origin: terminal hematuria, blood clots, normal morphology of urinary RBCs, and absent or minimal proteinuria

Acute nephritic syndrome is characterized by tea or cola-colored urine, facial edema (periorbital edema) or anasarca, hypertension, and oliguria. Symptoms of significant hypertension may be present (headache, altered sensorium, diplopia, epistaxis, heart failure).

Post-infectious glomerulonephritis is characterized by acute nephritic syndrome following 7 – 21 days after a group A β-hemolytic streptococcal pharyngitis or a skin infection. RPGN also presents with acute nephritic syndrome, but has a more aggressive course.

In children with IgA nephropathy, episodes of gross hematuria may follow upper respiratory infections or gastrointestinal infections. Other features include mild proteinuria and mild-moderate hypertension.

Clinical features of urinary tract infection include

  • Fever
  • Frequency of urine
  • Urgency of urination
  • Burning micturition
  • Vomiting
  • Flank pain
  • Hematuria
  • Costovertebral tenderness

Clinical features of urolithiasis include

  • Episodes of renal colic
  • Flank pain
  • Hematuria
  • Frequency of urination depending upon location of the stone

Clinical features of nephrocalcinosis include

HSP is a small vessel vasculitis characterized by purpuric rash, joint pain, and abdominal pain. Renal involvement is seen in approximately half of the patients. The condition resolves spontaneously. HUS is characterized by uremia, microangiopathic hemolytic anemia, and thrombocytopenia, mostly following infections with E. coli O157:H7.

Microscopic or gross hematuria may follow blunt abdominal trauma. Hematuria after a minor blunt abdominal trauma is highly suggestive of congenital anomalies, especially with >    50 RBCs/hpf in urine.

In a child with hematuria, family history is important in disorders like Alport syndrome, SLE nephritis, IgA nephropathy, thin glomerular basement membrane disease, polycystic kidney disease, sickle cell disease, and urolithiasis.

Alport’s syndrome is an x-linked disorder characterized by renal manifestations (recurrent hematuria, proteinuria, and renal insufficiency), high-frequency sensorineural hearing loss, and ocular manifestations (anterior lenticonus, retinal involvement). Thin GBM disease is characterized by persistent microscopic hematuria in absence of proteinuria, progressive renal insufficiency, hearing loss and ocular features.

Abdominal mass may be present in hydronephrosis, polycystic kidney disease, multicystic dysplastic kidney, or tumor. Skin rashes and arthritis suggest the possibility of SLE or HSP.

The loin pain hematuria syndrome is characterized by recurrent episodes of unilateral/bilateral lumbar pain with microscopic or macroscopic hematuria with normal renal function and normal genitourinary tract. Women in the age group of 20–40 years are most commonly affected, although it can be seen in children also. The diagnosis is made after the exclusion of other causes of hematuria. Approximately, half of the patients have psychological problems.

Idiopathic urethrorrhagia is characterized by terminal urethral hematuria and dysuria in prepubertal boys, due to bulbar urethral inflammation. Spontaneous resolution occurs in > 90 % of the patients and an endoscopy is usually unnecessary for evaluation.

In children with normal blood pressure, normal urine output, and absence of proteinuria, it is unlikely that microscopic hematuria warrants aggressive management, regardless of etiology.

Question Why
Recent sore throat or skin infection? Post-strep glomerulonephritis
Associated fever, dysuria or flank pain? Pyelonephritis
History of high blood pressure? Nephritic syndrome and renal involvement
Family history of deafness/renal disease? Alport syndrome
Chronic medical problems? SLE, sickle cell
History of purpuric rash, abdominal pain? Henoch-Schönlein purpura
History of trauma? Bleed in urinary tract

Diagnosis of Hematuria

Commercially available dipsticks can detect hematuria; however, dipsticks can give both false positive (urine pH > 9, contamination with hydrogen peroxide) and false negative (presence of formalin in urine sample or high intake of ascorbic acid) results. Hematuria diagnosed by dipsticks needs to be confirmed by microscopic examination of urine.

To confirm the presence of RBCs in the urine 10 mL of freshly centrifuged (2000 rpm for 5 minutes), the urine sample should be examined under microscope (400 x magnification).

After confirming the diagnosis of hematuria, appropriate laboratory investigations and imaging should be performed to identify the etiology.

Urine examination

  • Presence of proteinuria (> 100 mg/dL) suggests renal disease
  • Positive urine nitrites, positive urine leukocyte esterase, and presence of white blood cells (WBCs) in urine suggests a urinary tract infection (UTI)
  • Urine calcium:creatinine ratio > 0.2 mg/mg suggests hypercalciuria

Complete blood counts and peripheral smear

  • Anemia is present in acute renal failure (intravascular dilution due to hypervolemia), chronic renal failure (decreased production of RBCs), hemolysis (HUS or SLE), or blood loss (pulmonary hemorrhage in Goodpasture syndrome or malena in HSP or HUS)
  • It is rare to develop anemia due to blood loss from hematuria
  • Leukocytosis suggests pyelonephritis or urinary tract infection (Leukopenia is a feature of SLE)
  • Thrombocytopenia may be present in malignancies, SLE, HUS, renal vein thrombosis, etc.
  • Examination of a peripheral blood smear is helpful to reveal microangiopathic anemia in HUS

Other laboratory investigations

  • Elevated serum creatinine and blood urea suggests renal failure
  • Serum C3 and C4: PSGN, MPGN, or lupus nephritis are associated with hypocomplementemia
  • Serum antistreptolysin O (ASO) and anti-DNAase B are useful in the diagnosis of post-infective glomerulonephritis (throat and skin culture can be performed if indicated)
  • Serum antinuclear antibody (ANA) and anti-dsDNA antibody are useful in the diagnosis of SLE
  • Sickle cell preparation and hemoglobin electrophoresis are useful in the diagnosis of sickle cell trait or disease
  • Urine culture is helpful to diagnose a urinary tract infection
  • 24-hour urine for calcium, creatinine, uric acid and oxalate is helpful in the diagnosis of crystalluria, urolithiasis, and nephrocalcinosis
  • Coagulation studies are not helpful in the evaluation of a child with hematuria unless medical history or family history suggests the possibility of a bleeding disorder
  • It is important to remember that a bleeding disorder is an unusual cause of hematuria in children

Imaging studies

  • Renal ultrasonogram is the first modality of imaging in the evaluation of hematuria
  • Is especially useful in the evaluation of patients presenting with trauma, gross hematuria, abdominal pain, or flank pain
  • Spiral CT scan is better than ultrasonogram, but ultrasonography is often the first line imaging modality due to availability, cost, and safety
  • Voiding cystourethrogram (VCUG) is helpful in patients with hydronephrosis, hydroureter, urinary tract infection, renal scarring, and pyelocaliectasis
  • Cystoscopy is indicated in children with bladder mass seen on ultrasonogram, posterior urethral valves, urethral abnormalities caused by trauma, tumor, or rare true urethral stenosis. In other cases, cystoscopy is unnecessary (is also costly and carries a risk of anesthesia)
  • Indications of renal biopsy are recurrent gross hematuria with hypertension, proteinuria, and/or decreased renal function, as well as some children with persistent microscopic hematuria

Remember

  1. Most important tests for the initial evaluation of a child with microscopic hematuria are tests for proteinuria and microscopic examination of urine for RBCs and RBC casts!
  2. Most important tests for the initial evaluation of a child with gross hematuria are urine culture and renal ultrasonogram!

Differential Diagnoses of Hematuria

The presence of hemoglobin (hemolysis) and myoglobin (rhabdomyolysis) in urine causes heme-positive red urine. Certain drugs (rifampin, pyridium, deferoxamine, chloroquine, iron sorbitol, metronidazole, etc), dyes (aniline dye), and foods (beets, blackberries, food colors) can produce red, cola colored or burgundy urine. Presence of abnormal metabolites or pigments (homogentisic acid, melanin, methemoglobin, porphyrin, urate) in urine can also produce red, cola or dark colored urine.

Management of Hematuria

As hematuria is a sign and not a disease, the management of hematuria includes identification of the cause and treatment of the cause. There is no specific treatment of hematuria itself.

Some children have persistent asymptomatic isolated hematuria and normal laboratory evaluation. Parents of such children need reassurance; monitoring of blood pressure and urine examination should be done every 3 months until the resolution of the hematuria. Such children should be referred to a pediatric nephrologist if hematuria persists for more than 1 year.

Progression and Prognosis of Hematuria

The prognosis of children with hematuria is determined by the primary etiology of hematuria. In children with isolated microscopic hematuria without specific medical disorder, the prognosis is good.

Review Questions

1. Which of the following conditions is associated with a normal serum C3 level?

  1. IgA nephropathy
  2. Poststreptococcal glomerulonephritis
  3. Membranoproliferative glomerulonephritis
  4. Lupus nephritis

2. Which of the following is a characteristic ocular finding in children with Alport syndrome?

  1. Keratoconus
  2. Anterior lenticonus
  3. Brushfield spots
  4. Subcapsular cataract
  5. Hypopyon

3. In which of the following conditions, dipsticks can give false positive test results for hematuria?

  1. Contamination of urine with formalin
  2. High intake of ascorbic acid
  3. Significantly acidic urine
  4. Significantly alkaline urine
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