Hematuria

Updated: Feb 29, 2024
  • Author: Sanjeev Gulati, MD, MBBS, DNB(Peds), DM, DNB(Neph), FIPN(Australia), FICN, FRCPC(Canada); Chief Editor: Craig B Langman, MD  more...
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Overview

Practice Essentials

Generally, hematuria is defined as the presence of 5 or more red blood cells (RBCs) per high-power field in 3 of 3 consecutive centrifuged specimens obtained at least 1 week apart. (See the image below.) Hematuria can be either gross (ie, overtly bloody, smoky, or tea-colored urine) or microscopic. It may also be either symptomatic or asymptomatic, either transient or persistent, and either isolated or associated with proteinuria and other urinary abnormalities. [1]

Asymptomatic (isolated) hematuria generally does not require treatment. In conditions associated with abnormal clinical, laboratory, or imaging studies, treatment may be necessary, as appropriate, with the primary diagnosis.

Microscopy of urinary sediment. Typical appearance Microscopy of urinary sediment. Typical appearance in non-glomerular hematuria: RBCs are uniform in size and shape but show two populations of cells because a small number have lost their hemoglobin pigment.

Signs and symptoms

The first step in the evaluation of hematuria consists of a detailed history and a thorough physical examination. Efforts should be made to distinguish glomerular causes from extraglomerular ones, as follows:

  • Passage of clots in urine suggests an extraglomerular cause.

  • Fever, abdominal pain, dysuria, frequency, and recent enuresis in older children may point to a urinary tract infection as the cause.

  • Recent trauma to the abdomen may be indicative of hydronephrosis.

  • Early-morning periorbital puffiness, weight gain, oliguria, dark-colored urine, and edema or hypertension suggest a glomerular cause.

  • Hematuria due to glomerular causes is painless.

  • Recent throat or skin infection may suggest postinfectious glomerulonephritis.

  • Joint pains, skin rashes, and prolonged fever in adolescents suggest a collagen vascular disorder.

  • Anemia cannot be accounted for by hematuria alone; in a patient with hematuria and pallor, other conditions should be considered.

  • Skin rashes and arthritis can occur in Henoch-Schönlein purpura and systemic lupus erythematosus.

  • Information regarding exercise, menstruation, recent bladder catheterization, intake of certain drugs or toxic substances, or passage of a calculus may also assist in the differential diagnosis.

  • A family history that is suggestive of Alport syndrome, collagen vascular diseases, urolithiasis, or polycystic kidney disease is important.

Physical examination should include the following:

  • Measurement of the blood pressure (with an appropriately sized cuff)

  • Evaluation for the presence of periorbital puffiness or peripheral edema

  • Detailed skin examination to look for purpura and/or petechiae

  • Abdominal examination to look for palpable kidneys

  • Careful examination of the genitalia

  • Detailed ophthalmologic evaluation (in familial hematuria)

The following findings help distinguish between glomerular and nonglomerular hematuria:

  • Glomerular hematuria: Brown-colored urine, RBC casts, and dysmorphic (small, deformed, misshapen, sometimes fragmented) RBCs and proteinuria

  • Nonglomerular hematuria: Reddish or pink urine, passage of blood clots, and eumorphic (normal-sized, biconcavely shaped) erythrocytes

See Clinical Presentation for more detail.

Diagnosis

The laboratory tests ordered for the evaluation of hematuria must be based on the clinical history and the physical examination. Tests that may be helpful include the following:

  • Urinalysis with careful microscopic review of the urine sample.

  • Phase-contrast microscopy to help determine the source of the bleeding. In clinical practice this test is not always feasible.

  • Electrolyte, blood urea nitrogen (BUN), and serum creatinine levels.

  • Hematologic and coagulation studies (eg, complete blood count [CBC] and, sometimes, platelet counts).

  • Random urine calcium and creatinine levels.

  • Serologic testing (eg, complement, antistreptolysin [ASO], anti-DNase B, antinuclear antibody [ANA], and double-stranded DNA [dsDNA], ANCA).

  • Urine culture for suspected urinary tract infection (UTI).

The following imaging studies may be helpful:

  • Renal and bladder ultrasonography

  • Spiral computed tomography (CT)

  • Voiding cystourethrography

  • Radionuclide studies

Intravenous urography rarely contributes additional information in the evaluation of hematuria and results in unnecessary exposure to ionizing radiation.

A kidney biopsy is rarely indicated in the evaluation of isolated asymptomatic hematuria. Relative indications for performing a kidney biopsy in patients with hematuria are as follows:

  • Significant proteinuria

  • Abnormal renal function

  • Recurrent persistent hematuria

  • Serologic abnormalities (abnormal complement, ANA, or dsDNA levels)

  • Recurrent gross hematuria

  • A family history of end-stage renal disease

In most patients, a renal biopsy either is normal or reveals minor changes, such as thin glomerular basement membranes, focal glomerulonephritis, or mild mesangial hypercellularity. In a minority of patients, histologic findings, together with historical or serologic data, may point to specific conditions.

Hematuria may be categorized as follows:

  • Gross hematuria

  • Microscopic hematuria with clinical symptoms

  • Asymptomatic microscopic hematuria with proteinuria

  • Asymptomatic microscopic (isolated) hematuria

See Workup for more detail.

Management

General principles of treatment are as follows:

  • Hematuria is a sign and not itself a disease; thus, therapy should be directed at the cause.

  • Asymptomatic (isolated) hematuria generally does not require treatment.

  • In conditions associated with abnormal clinical, laboratory, or imaging studies, treatment may be necessary, as appropriate, with the primary diagnosis.

  • Surgical intervention may be necessary with certain anatomic abnormalities (eg, ureteropelvic junction obstruction, tumor, or significant urolithiasis) but not necessarily to treat hematuria.

  • Unlike in adults, cystoscopy does not contribute to the diagnosis in the majority of children.

  • Dietary modification is usually not indicated.

  • Patients with persistent microscopic hematuria should be monitored every 6-12 months for the appearance of signs or symptoms indicative of progressive renal disease.

See Treatment and Medication for more detail.

Guidelines on hematuria from the American College of Physicians (ACP) advise that clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria. [2]

The ACP also makes the following recommendations [2] :

  • Clinicians should confirm heme-positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic patients.

  • Clinicians should pursue evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy.

  • Clinicians should not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria.

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Background

Hematuria is one of the most common urinary findings that result in children presenting to pediatric nephrologists. Generally, hematuria is defined as the presence of 5 or more RBCs per high-power field in 3 of 3 consecutive centrifuged specimens obtained at least 1 week apart. In the office setting, a positive reaction on the urine "dipstick" test is usually the first indication of the presence of hematuria. Hematuria can be gross (ie, the urine is overtly bloody, smoky, or tea colored) or microscopic. It may be symptomatic or asymptomatic, transient or persistent, and either isolated or associated with proteinuria and other urinary abnormalities.

Hematuria should be confirmed by the demonstration of blood on screening urinalysis or by direct visualization with urine microscopy. Commercially available urine dipstick screening tests are very sensitive for the presence of heme protein in urine.

Because urine dipstick screening tests are highly sensitive, pediatricians should be aware of the many common causes of false-positive urinalysis results for blood. In patients with rhabdomyolysis, the presence of myoglobin in the urine, which is a structurally similar pigment protein, can result in a false-positive dipstick test for blood without true hematuria. Heme-positive urinalyses that are negative for blood on microscopy can also be caused by intravascular hemolysis, as well as contamination with povidone-iodine or other oxidizing substances. In addition, excluding discoloration of the urine from the ingestion of various foods (eg, beets, rhubarb, and blackberries) or medications (eg, rifampicin, nitrofurantoin, and metronidazole) is important.

In contrast, false-negative dipstick tests despite the presence of hematuria could result from dilute urine specimens, highly acidic urine pH (< 5), and the presence of reducing substances (such as ascorbic acid). [1]

The role of the primary care pediatrician in the management of a child with hematuria includes the following:

  • Recognize and confirm the finding of hematuria

  • Initiate a preliminary diagnostic workup to try to identify common etiologies

  • Select patients who have significant urinary system disease that might require further referral for diagnosis or management

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Pathophysiology

The etiology and pathophysiology of hematuria vary. For instance, hematuria of glomerular origin may be the result of a structural disruption in the integrity of the glomerular basement membrane caused by inflammatory or immunologic processes. [3] Chemicals may cause toxic disruptions of the renal tubules, whereas calculi may cause mechanical erosion of mucosal surfaces in the genitourinary tract, resulting in hematuria.

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Etiology

Hematuria can be of glomerular or nonglomerular origin. Brown-colored urine, RBC casts, and dysmorphic (small deformed, misshapen, sometimes fragmented) RBCs and proteinuria are suggestive of glomerular hematuria. Reddish or pink urine, passage of blood clots, and eumorphic (normal sized, biconcavely shaped) erythrocytes are suggestive of a nonglomerular bleeding site.

Potential causes of glomerular hematuria in children include the following:

Potential causes of nonglomerular hematuria in children include the following:

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Epidemiology

United States data

The prevalence of gross hematuria in children is estimated to be 0.13%. In more than half of the cases (56%), this is due to an easily identifiable cause. The most common cause appears to be cystitis (20-25%). Asymptomatic microscopic hematuria is, on average, 10-fold as prevalent as gross hematuria (1.5%, range 0.4-4.1%, depending on the criteria used to define hematuria). With repeated evaluations, the prevalence of asymptomatic microscopic hematuria decreases to less than 0.5%, supporting the notion that most cases of hematuria in children are transient. [1]

The incidence of simultaneous hematuria and proteinuria is estimated to be only 0.06%, but their coexistence signals significant renal disease. Hematuria or proteinuria that persists on repeated investigations warrants additional evaluation. [4]

Race-, sex-, and age-related demographics

The incidence of hematuria in specific racial groups is determined by the primary cause. For example, idiopathic hypercalciuria is infrequent in Black and Asian children but relatively common in Whites. Conversely, hematuria caused by sickle cell disease is more common in Blacks and Hispanics than in Whites. IgA nephropathy is more prevalent among patients with European or Asian ancestry than among those with African ancestry. [5]

Sex may predispose a child to specific diseases that manifest as hematuria. For example, the sex-linked form of Alport syndrome has a male preponderance, whereas lupus nephritis tend to be more common in adolescent girls.

Prevalence of certain conditions varies with age. [3]  For instance, Wilms tumors are more frequent in children of preschool age, whereas acute postinfectious glomerulonephritis is more frequent in the school-aged population. In adults, hematuria is often a sign of malignancy of the genitourinary tract (eg, renal cell carcinoma, bladder tumors, prostatic tumors). These conditions are rare in children.

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Prognosis

Morbidity/mortality

In general, children with isolated asymptomatic microscopic hematuria tend to do well, whereas those with associated findings (eg, hypertension, proteinuria, abnormal serum creatinine levels) are more likely to have serious problems. Because hematuria is the end result of various processes, the morbidity and mortality rates of the condition depend on the primary process that initiated it.

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Patient Education

Inform children and their parents that strenuous exercise may aggravate hematuria; however, hematuria by itself should not prevent the child from participating in sports. Despite the sometimes alarming intensity or persistence of hematuria, parents must be informed that, by itself, hematuria rarely causes anemia.

For helpful patient education resources, see the article Blood in Urine (Hematuria).

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