Table of Contents

 

1. Abstract
2. Case Presentations
3. Introduction for Management Of Hematuria In Children
4. Critical Appraisal Of The Literature
5. Epidemiology
   1. Macroscopic (Gross) Hematuria
   2. Microscopic Hematuria
6. Pathophysiology
7. Etiology And Differential Diagnosis
   1. Glomerular Causes
      1. Primary Glomerular Causes
      2. Systemic Glomerular Causes
   2. Nonglomerular Renal Causes
   3. Extrarenal Causes
   4. Trauma
8. Prehospital Care
9. Emergency Department Evaluation
   1. History
   2. Physical Examination
10. Diagnostic Studies
    1. Laboratory Evaluation
    2. Imaging
11. Treatment
12. Disposition
13. Special Circumstances/Populations
14. Controversies And Cutting Edge
15. Summary
16. Risk Management Pitfalls In The Evaluation And Management Of Hematuria
17. Time- And Cost-Effective Strategies
18. Case Conclusions
19. Clinical Pathway For Management Of Hematuria In Children
20. Tables and Figures
    1. Table 1. Causes Of Red Urine Without
    2. Table 2. Differentiating Glomerular From Nonglomerular Causes Of Hematuria
    3. Table 3. Etiology Of Hematuria
    4. Table 4. Criteria For Hospitalization
    5. Table 5. Criteria To Consult Or Refer To A Nephrologist
    6. Table 6. Criteria To Consult Or Refer To A Urologist
    7. Figure 1. Samples Of Macroscopic And Microscopic Hematuria
21. References

Abstract

Hematuria is defined as an abnormal number of red blood cells in urine. Even a tiny amount of blood (1 mL in 1000 mL of urine) is sufficient to make urine appear pink or red. In the pediatric population, the majority of etiologies are benign and often asymptomatic. However, hematuria may also be a sign of renal pathology, local infection, or systemic disease. Hematuria can be differentiated into 2 categories: macroscopic hematuria (visible to the naked eye) and microscopic hematuria (> 5 red blood cells/high-powered field on urinalysis). This review will outline the current literature regarding evaluation and management of pediatric patients who present to the emergency department with hematuria. Obtaining a thorough history and the appropriate diagnostic tests will be discussed in depth.

Case Presentations

A 12-year-old adolescent boy presents to the emergency department with a chief complaint of urine the color of brown soda. He reports a recent upper respiratory infection. On physical examination, his blood pressure is 145/72 mm Hg, and you note periorbital edema. Urine dipstick is positive for blood and 2+ protein. You consider any emergent laboratory work you need to perform to confirm the diagnosis and wonder if this child requires admission to the hospital…

A 15-year-old adolescent girl is brought in by her parents with a chief complaint of pink urine. Review of systems is significant for muscle soreness, which she attributes to running a half-marathon for her cross-country team the day prior to presentation. Urine dipstick is positive for large occult blood. As you begin initial management, you consider other laboratory work that should be performed…

A previously healthy 5-year-old girl presents to the emergency department with pink urine after visiting her grandmother for the weekend. Review of systems is otherwise negative, and the patient does not take any medications. The physical examination is nonfocal, including the genitourinary examination. Urine dipstick is negative for blood or protein. You wonder what other questions you should ask to confirm the diagnosis. Does she require a repeat urine dipstick and microscopic urinalysis with her pediatrician?

Introduction for Management Of Hematuria In Children

Hematuria is an abnormal number of red blood cells (RBCs) in urine and is the chief complaint for 0.1% to 0.15% of pediatric acute care visits.¹ Hematuria is often defined > 5 RBCs per high-powered field (HPF).^2,3 Even a tiny amount of blood (1 mL in 1000 mL of urine) is sufficient to make urine appear pink or red.⁴ It can be categorized by gross hematuria (visible to the naked eye) or microscopic hematuria (seen on urine dipstick or urinalysis). It is important to distinguish between macroscopic and microscopic hematuria, as the etiologies can be very different. It is also important to determine whether the etiology of the hematuria is glomerular versus nonglomerular and to be aware of the systemic complications associated with the various causes of hematuria. Obtaining a thorough history is key to determining the necessity of testing, the appropriate treatment, and disposition.

The urine dipstick test is the most common initial screening test to determine whether there is blood in the urine. The test utilizes the peroxidase activity of hemoglobin to catalyze a chemical reaction that converts chromogen tetramethylbenzidine to an oxidized chromogen, which has a green-blue color.⁵ This testing has a reported sensitivity as high as 100% and a specificity of 99% to detect 5 to 10 RBC/mcL (which is roughly 2-5 RBC/HPF on microscopic urinalysis).⁶ A urine dipstick that is positive for blood with no RBCs seen on urine microscopy suggests myoglobinuria. A urine dipstick may be positive for proteinuria in the setting of hematuria, but should not exceed 2+ (100 mg/dL) if the only source of protein is from hematuria.⁷

False positives can occur due to alkaline urine (pH > 9), microbial peroxidase associated with urinary tract infections, or oxidizing agents used to clean the perineum (eg, hypochlorite). False negatives may be due to formalin, a large amount of nitrites, a high specific gravity, or a high concentration of ascorbic acid.

In most instances, the etiology of the hematuria is not life-threatening, and clinicians can provide reassurance and recommend outpatient follow-up.

Critical Appraisal Of The Literature

An online search was performed for literature from 1970 to the present using the Pubmed and Ovid MEDLINE® databases. The areas of focus were hematuria and pediatrics. Multiple search terms were used, including pediatric hematuria, gross hematuria, macroscopic hematuria, microscopic hematuria, urine dipstick, proteinuria, and evaluation of hematuria. More than 100 articles, including case reports and retrospective studies, were analyzed and 80 articles were identified as pertinent to this review. There is a significant amount of literature on pediatric hematuria, but a dearth of literature on the evaluation and acute management of hematuria in the pediatric emergency department (ED).

Risk Management Pitfalls In The Evaluation And Management Of Hematuria

1. “Hematuria can account for 3+ protein in the urine.” Proteins are excreted with hematuria; however, gross hematuria does not account for > 2+ proteinuria on dipstick. Any level > 2+ protein should raise concern for glomerular disease.^7,23
2. “A lack of RBCs on urinalysis in a trauma patient rules out intra-abdominal injury.” Recent studies have shown that urologic injuries can occur with and without hematuria on urinalysis.^61,62 Urine dipsticks are often poor screening tests for urinary tract injury due to false positives and false negatives.⁶⁰ Emergency clinicians should consider the mechanism of action, abdominal examination findings, and urinalysis results when considering further imaging in trauma patients.
3. “Every patient with microscopic hematuria needs a nephrology referral.” Patients with asymptomatic isolated microscopic hematuria and a normal physical examination can follow up with a primary care provider. A urine dipstick and microscopic urinalysis should be repeated 2 times within 2 weeks by a primary care provider.²⁶ Patients with hematuria and proteinuria or symptomatic hematuria require further evaluation, which may include a referral to a nephrologist.
4. “Every pediatric patient with microscopic hematuria needs emergent imaging.” For most cases of isolated microscopic hematuria, no imaging is necessary. For cases associated with trauma or if urolithiasis is suspected, consider emergent imaging. A renal ultrasound is necessary for gross hematuria.
5. “Every pediatric patient with urolithiasis requires hospital admission.” If the stone is < 4 mm in size, there is a high likelihood of passing. As long as pain control can be achieved with oral pain medications and the patient can maintain hydration, the patient does not require admission to the hospital.
6. “Gross hematuria is most commonly due to trauma and requires a trauma or urology consultation.” In several studies of patients presenting with gross hematuria, the most common cause was urinary tract infection (14%-50%) followed by perineal/urethral irritation (11%-18%), and underlying congenital anomalies (13%). Trauma only accounted for 7% of patients with gross hematuria.^1,13,14 Additionally, in a study by Bergstein et al, the most common cause of gross hematuria was hypercalciuria.^14,15 A careful review of the patient’s history and physical examination should be taken into account prior to referral.
7. “A full workup should be pursued until an etiology is found for microscopic hematuria.” In many cases of microscopic hematuria, no diagnosis is made after evaluation (30%-80%).^12,14,18,22
8. “Normotensive patients with postinfectious or poststreptococcal glomerulonephritis should be admitted or observed for blood pressure monitoring.” Patients without significant edema or hypertension can be discharged and followed closely by a primary care provider. Hematuria and proteinuria should resolve within a few weeks to months.²⁷
9. “Urolithiasis is typically seen on renal ultrasound.” Although renal ultrasound avoids radiation, it can often miss small stones ( < 3 mm) and stones in certain areas of the renal tract. Patients with nondiagnostic ultrasounds should have a spiral CT scan if there is concern for urolithiasis.
10. “Patients with Henoch-Schönlein purpura often present with hematuria as the chief complaint.” Fifty percent of children with Henoch-Schönlein purpura have renal involvement (including transient hematuria and proteinuria); however, they rarely present with hematuria as the chief complaint.⁴⁰ Relapses and remissions can manifest as episodes of gross hematuria, though only 2% develop long-term renal insufficiency.^41,42

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available. The most informative references cited in this paper, as determined by the author, will be noted by an asterisk (*) next to the number of the reference.

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