The ABC’s of evaluating children with hematuria
Richard E. Neiberger
Hematuria in children may be gross or microscopic, painful or painless, symptomatic or asymptomatic, intermittent, transient or persistent.[1-3] Red urine or a positive dipstick test for blood must be confirmed with a microscopic examination for red blood cells. Urine culture is always indicated, particularly if white blood cells or bacteria are seen.
If asymptomatic microscopic hematuria in the absence of infection is found during a routine clinical evaluation, confirmation of the persistence of the hematuria is necessary, since isolated hematuria in children is transient in most cases. It is reasonable m an asymptomatic child to examine the urine for red blood cells on at least three occasions, one to three months apart, before starting an extensive evaluation.
Parents are usually greatly concerned when they notice gross hematuria or when a physician reports that red blood cells were found in their child’s urine. They usually fear kidney failure or cancer, perhaps because of experiences with an older acquaintance or relative. Worried parents should be informed that while these serious disorders are possible in children, they occur much less frequently in children than in adults.
ABC’s of Childhood Hematuria
The ABC mnemonic was developed to facilitate recall of the differential diagnosis for childhood hematuria. Table 1 lists the most likely causes of hematuria at different ages.
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Not every test mentioned must be performed on each child. A careful history and physical examination are always necessary, however; they may provide valuable clues to the diagnosis and help in deciding which tests should be performed.
The differential diagnosis for childhood hematuria can be remembered by thinking of the alphabet, A through I. Table 2 indicates the components of a medical evaluation that are helpful for each disorder. It should be noted that a careful history applies to all categories. An algorithmic approach to evaluation is shown in Figure 1.
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A = ANATOMY
Anatomic causes of hematuria include renal cysts, arteriovenous malformations, renal venous entrapment and obstruction with hydronephrosis. Malformations may be associated with microscopic or gross hematuria. A family history of polycystic kidney disease is occasionally elicited. Sometimes an abdominal mass can be palpated. A renal ultrasound examination is the most useful study for demonstrating anatomic abnormalities. In children, intravenous pyelogram, magnetic resonance imaging and computed tomography are rarely necessary.
B = BOULDERS
“Boulders” is a descriptive term that includes large renal stones, hypercalciuria and hyperuricosuria.[5,8] Large stones, which are infrequent in children, may be manifested by pain and gross hematuria. Hypercalciuria and hyperuricosuria are often associated with asymptomatic microscopic hematuria and are much more frequent causes of hematuria in children than renal stones. If the spot urine ratio of calcium or uric acid to creatinine is greater than 0.2, a 24-hour urine collection will be useful for determining the excretion rate; an excretion rate for calcium or uric acid over 4 mg per kg per day is abnormal. A history of previous stones or stones in immediate relatives is helpful. Stones can often be detected on renal sonogram.
C = CANCER
Cancer is a rare cause of hematuria in children. Cancers that can cause hematuria include Wilms’ tumor, adenocarcinoma and infiltration of the kidney by leukemia or solid tumors. Children seldom present with hematuria as the primary or sole symptom of cancer.
On physical examination, the patient with cancer may demonstrate severe pallor, or an abdominal mass may be found. The complete blood count may reveal findings indicative of hematogenous cancer. Renal sonogram may show Wilms’ tumor, neuroblastoma or infiltration of the kidney by an adjacent tumor.
D = DRUGS
Hematuria may be drug-related. The patient may have taken prescriptive, over-the counter or illicit drugs. Frequent offenders among medications include methicillin (Staphcillin), cyclophosphamide (Cytoxan, Neosar) and anticoagulants. In a child with hematuria who is taking medication, the possibility of a cause-and-effect relationship between the drug and the hematuria should be kept in mind.
The history is the most important component of this evaluation. When the patient has been taking a drug known to be associated with hematuria, the absence of other symptoms or physical findings should prompt discontinuation of the drug, if possible, before an extensive evaluation for other causes of hematuria is undertaken. In patients suspected of illicit drug use, a urinalysis for toxicology (heroin, cocaine, etc.) may be helpful.
E = EXERCISE
Exercise-induced hematuria (marathon runners’ hematuria) is a diagnosis of exclusion. Exercise-induced hematuria does not occur in younger children. Athletes participating in a variety of contact and noncontact sports, including rowing, lacrosse, football and track, frequently have hematuria. However, as more and more young males and females age 12 to 21 years are becoming involved in cross-country running and other forms of strenuous exercise, this diagnosis should be considered when an appropriate history is given and other, more likely possibilities are excluded.
F = FOREIGN BODY, FAMILIAL OR FACTITIOUS
Foreign bodies placed in the urethra by small children may cause hematuria, as may blunt renal trauma. Bladder catheterization or other instrumentation may cause trauma to the urethra and result in hematuria. The history should uncover trauma to the urinary tract or kidney, if it was significant enough to cause bleeding. (Menstruation as a cause for red blood cells in the urine can be identified by the history.)
Familial hematuria may be benign or may produce end-stage renal disease (Alport’s syndrome). Evaluation for familial hematuria should include a careful physical examination and urinalysis in both the patient and first-degree relatives.
Factitious hematuria is caused by any of a large number of substances that can tum the urine red.[13,14] Two causes of “red diaper” in infants should be mentioned. There is a report on a group of healthy infants whose soiled diapers developed a red color after 24 to 36 hours of incubation. The red color was attributed to Serratia marcescens. Because disposable diapers are so commonly used nowadays, this phenomenon is rarely seen. Instead, non-hemoglobin red diaper is usually associated with urate crystals. In both cases, the diaper may be quite red; however, when the patient’s urine is tested for hemoglobin or examined microscopically for erythrocytes, neither is found.
When the dipstick test for heme pigments is positive, a distinction should be made between erythrocytes and other sources of heme pigments. Erythrocytes can be concentrated by centrifugation and detected by microscopic examination.
Hemoglobinuria can be differentiated from myoglobinuria by testing plasma. Plasma from patients with hemoglobinemia is pink, and the O-toluidine test is positive. The plasma is clear and the O-toluidine test is negative in patients with myoglobinuria.
G = GLOMERULONEPHRITIS
Glomerulonephritis may cause gross or microscopic hematuria. In the earliest stages, hematuria may be only microscopic. As glomerulonephritis progresses, proteinuria, hypertension and decreased creatinine clearance develop. The single most important finding consistent with glomerulonephritis is red blood cell casts in the urine; however, their absence does not exclude glomerulonephritis.
Physical findings may include pallor, hypertension, fever and skin rash (the last, in cases of glomerulonephritis associated with Henoch-Schonlein purpura).
In acute poststreptococcal glomerulonephritis, the history may contribute information regarding a previous pharyngeal or skin infection. Other abnormalities in glomerulonephritis include elevated blood urea nitrogen and creatinine levels, anti-DNAase B and antistreptolysin-O titers, low complement components (C3 and C4) and positive antinuclear antibody response. In patients with nephritis, renal ultrasound frequently demonstrates increased echogenicity. Referral to a pediatric nephrologist and percutaneous renal biopsy may be indicated in the evaluation of children with glomerulonephritis.
H = HEMATOLOGY
Hematologic causes of hematuria can be divided into two groups, hemoglobinopathies and coagulopathies. Hemoglobinopathies with associated hematuria are relatively common. Hematuria may occur in children with hemoglobin SS, hemoglobin AS and hemoglobin SC.
Hematuria can be associated with coagulation defects, but it is rarely an initial presentation. The most helpful components of the evaluation include a history of hemoglobinopathy or coagulation disorders, with bruising or purpura discovered on physical examination. Hemoglobin electrophoresis and determination of partial thromboplastin time or prothrombin time may be useful.
I = INFECTION
Infection is a frequent cause of hematuria in children. Viral, bacterial or fungal infection anywhere along the urinary tract may cause hematuria. Bacterial infection commonly causes microscopic hematuria. Cystitis caused by adenovirus is frequently hemorrhagic.tuberculosis of the kidney can lead to hematuria, but disseminated tuberculosis is a very rare cause of hematuria in children in the United States.
The patient’s history, standard urinalysis and cultures are useful in most cases. Special bacterial, viral and fungal cultures are occasionally helpful. A tuberculosis skin test is indicated in at-risk children who have not been tested recently.
The ABC’s of hematuria in children were initially developed to teach medical students a simple way to remember a relatively complete evaluation of the child with microscopic or gross hematuria. Subsequently, the mnemonic has been used to teach house staff and physicians in continuing education programs. It is my hope it will also be useful to any practicing physician who treats children, and improve their evaluation and care.
The author thanks Elizabeth S. Patrick for editorial assistance and manuscript preparation, and Jose H. Iglesias, M.D., Susan F. Massengill, M.D., and Alton Stocks, M.D., for constructive comments.
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