An Evidence-Based Approach To The Management Of Hematuria In Children In The Emergency Department

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.

1. * Ingelfinger JR, Davis AE, Grupe WE. Frequency and etiology of gross hematuria in a general pediatric setting. Pediatrics. 1977;59(4):557-561. (Retrospective review; 128,395 pediatric patients)
2. Feld LG, Waz WR, Perez LM, et al. Hematuria. An integrated medical and surgical approach. Pediatr Clin North Am. 1997;44(5):1191-1210. (Review)
3. * Diven SC, Travis LB. A practical primary care approach to hematuria in children. Pediatr Nephrol. 2000;14(1):65-72. (Review)
4. Phadke KD, Vijayakumar M, Sharma J, et al. Consensus statement on evaluation of hematuria. Indian Pediatr. 2006;43(11):965-973. (Consensus statement)
5. Meadow SR. Hematuria. In: Postlethwaite RJ, ed. Clinical Paediatric Nephrology. 2nd ed. Boston: Oxford University Press; 1994:1-14. (Textbook)
6. Moore GP, Robinson M. Do urine dipsticks reliably predict microhematuria? The bloody truth! Ann Emerg Med. 1988;17(3):257-260. (Prospective study; 2000 urine dipsticks, 2 brands)
7. Patel HP. The abnormal urinalysis. Pediatr Clin North Am. 2006;53(3):325-337. (Review)
8. Vehaskari VM, Rapola J, Koskimies O, et al. Microscopic hematuria in school children: epidemiology and clinicopathologic evaluation. J Pediatr. 1979;95(5 Pt 1):676-684. (Prospective population-based study; 8954 children)
9. * Lieu TA, Grasmeder HM, 3rd, Kaplan BS. An approach to the evaluation and treatment of microscopic hematuria. Pediatr Clin North Am. 1991;38(3):579-592. (Review)
10. * Quigley R. Evaluation of hematuria and proteinuria: how should a pediatrician proceed? Curr Opin Pediatr. 2008;20(2):140-144. (Review)
11. Barratt J, Feehally J. Treatment of IgA nephropathy. Kidney Int. 2006;69(11):1934-1938. (Review)
12. Chandar J, Gomez-Marin O, del Pozo R, et al. Role of routine urinalysis in asymptomatic pediatric patients. Clin Pediatr (Phila). 2005;44(1):43-48. (Retrospective study; 239 patients)
13. * Greenfield SP, Williot P, Kaplan D. Gross hematuria in children: a ten-year review. Urology. 2007;69(1):166-169. (Retrospective study; 342 patients)
14. * Bergstein J, Leiser J, Andreoli S. The clinical significance of asymptomatic gross and microscopic hematuria in children. Arch Pediatr Adolesc Med. 2005;159(4):353-355. (Prospective study; 274 patients)
15. Feld LG, Meyers KE, Kaplan BS, et al. Limited evaluation of microscopic hematuria in pediatrics. Pediatrics. 1998;102(4):E42. (Retrospective study; 325 patients)
16. Dodge WF, West EF, Smith EH, et al. Proteinuria and hematuria in schoolchildren: epidemiology and early natural history. J Pediatr. 1976;88(2):327-347. (Prospective populationbased study; over 12,000 patients)
17. Parekh DJ, Pope JC, Adams MC, et al. The association of an increased urinary calcium-to-creatinine ratio, and asymptomatic gross and microscopic hematuria in children. J Urol. 2002;167(1):272-274. (Prospective study; 96 patients)
18. Lee YM, Baek SY, Kim JH, et al. Analysis of renal biopsies performed in children with abnormal findings in urinary mass screening. Acta Paediatr. 2006;95(7):849-853. (Retrospective study; 461 patients)
19. Cho BS, Kim SD. School urinalysis screening in Korea. Nephrology (Carlton). 2007;12 Suppl 3:S3-S7. (Retrospective population-based study; 5 million patients)
20. Hisano S, Ueda K. Asymptomatic haematuria and proteinuria: renal pathology and clinical outcome in 54 children. Pediatr Nephrol. 1989;3(3):229-234. (Retrospective study; 54 patients)
21. Collar JE, Ladva S, Cairns TD, et al. Red cell traverse through thin glomerular basement membranes. Kidney Int. 2001;59(6):2069-2072. (Laboratory study)
22. Meyers KE. Evaluation of hematuria in children. Urol Clin North Am. 2004;31(3):559-573. (Review)
23. * Pan CG. Evaluation of gross hematuria. Pediatr Clin North Am. 2006;53(3):401-412, vi. (Review)
24. Carapetis JR, Steer AC, Mulholland EK, et al. The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005;5(11):685-694. (Review)
25. Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal glomerulonephritis. J Am Soc Nephrol. 2008;19(10):1855-1864. (Review)
26. Robson WL, Leung AK. Post-streptococcal glomerulonephritis with minimal abnormalities in the urinary sediment. J Singapore Paediatr Soc. 1992;34(3-4):232-234. (Case report; 1 patient)
27. Ofek I, Kaplan O, Bergner-Rabinowitz S, et al. Antibody tests in streptococcal pharyngitis. Streptozyme versus conventional methods. Clin Pediatr (Phila). 1973;12(6):341-344. (Prospective comparison laboratory study)
28. Utsunomiya Y, Koda T, Kado T, et al. Incidence of pediatric IgA nephropathy. Pediatr Nephrol. 2003;18(6):511-515. (Retrospective study; 270,902 patients)
29. Johnston PA, Brown JS, Braumholtz DA, et al. Clinicopathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry. Q J Med. 1992;84(304):619-627. (Retrospective study and data analysis)
30. Kashtan CE. Familial hematuria. Pediatr Nephrol. 2009;24(10):1951-1958. (Review)
31. Alamartine E, Sabatier JC, Guerin C, et al. Prognostic factors in mesangial IgA glomerulonephritis: an extensive study with univariate and multivariate analyses. Am J Kidney Dis. 1991;18(1):12-19. (Univariate statistical and multivariate regreession study; 282 patients)
32. Pescucci C, Longo I, Bruttini M, et al. Type-IV collagen related diseases. J Nephrol. 2003;16(2):314-316. (Review)
33. McCarthy PA, Maino DM. Alport syndrome: a review. Clin Eye Vis Care. 2000;12(3-4):139-150. (Review)
34. Jais JP, Knebelmann B, Giatras I, et al. X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a “European Community Alport Syndrome Concerted Action” study. J Am Soc Nephrol. 2003;14(10):2603-2610. (Data analysis; 195 families)
35. Savige J, Gregory M, Gross O, et al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol. 2013;24(3):364-375. (Clinical practice guidelines)
36. Hogg RJ, Harris S, Lawrence DM, et al. Renal tract abnormalities detected in Australian preschool children. J Paediatr Child Health. 1998;34(5):420-424. (Prospective study; 9355 patients)
37. Ritchie CD, Bevan EA, Collier SJ. Importance of occult haematuria found at screening. Br Med J (Clin Res Ed). 1986;292(6521):681-683. (Retrospective study; 10,050 patients)
38. Savige J, Rana K, Tonna S, et al. Thin basement membrane nephropathy. Kidney Int. 2003;64(4):1169-1178. (Review)
39. Kodner CM, Kudrimoti A. Diagnosis and management of acute interstitial nephritis. Am Fam Physician. 2003;67(12):2527-2534. (Review)
40. Rai A, Nast C, Adler S. Henoch-Schönlein purpura nephritis. J Am Soc Nephrol. 1999;10(12):2637-2644. (Review)
41. Koskimies O, Mir S, Rapola J, et al. Henoch-Schönlein nephritis: long-term prognosis of unselected patients. Arch Dis Child. 1981;56(6):482-484. (Case series; 141 children)
42. Coppo R, Mazzucco G, Cagnoli L, et al. Long-term prognosis of Henoch-Schönlein nephritis in adults and children. Italian Group of Renal Immunopathology Collaborative Study on Henoch-Schönlein purpura. Nephrol Dial Transplant. 1997;12(11):2277-2283. (Multicenter collaborative study; 152 patients)
43. Chen CY, Lin YR, Zhao LL, et al. Clinical spectrum of rhabdomyolysis presented to pediatric emergency department. BMC Pediatr. 2013;13:134. (Retrospective chart analysis; 37 patients)
44. Freedman AL. Urologic diseases in North America Project: trends in resource utilization for urinary tract infections in children. J Urol. 2005;173(3):949-954. (Database review)
45. Chang SL, Shortliffe LD. Pediatric urinary tract infections. Pediatr Clin North Am. 2006;53(3):379-400. (Review)
46. Stapleton FB. Idiopathic hypercalciuria: association with isolated hematuria and risk for urolithiasis in children. The Southwest Pediatric Nephrology Study Group. Kidney Int. 1990;37(2):807-811. (Prospective multicenter study; 215 patients)
47. Stapleton FB, Roy S, Noe HN, et al. Hypercalciuria in children with hematuria. N Engl J Med. 1984;310(21):1345-1348. (Prospective study; 83 patients)
48. Butani L, Kalia A. Idiopathic hypercalciuria in children--how valid are the existing diagnostic criteria? Pediatr Nephrol. 2004;19(6):577-582. (Review)
49. Ronnefarth G, Misselwitz J. Nephrocalcinosis in children: a retrospective survey. Members of the Arbeitsgemeinschaft fur padiatrische Nephrologie. Pediatr Nephrol. 2000;14(10- 11):1016-1021. (Retrospective study; 152 patients)
50. Moxey-Mims MM, Stapleton FB. Hypercalciuria and nephrocalcinosis in children. Curr Opin Pediatr. 1993;5(2):186-190. (Review)
51. Pietrow PK, Pope JC 4th, Adams MC, et al. Clinical outcome of pediatric stone disease. J Urol. 2002;167(2 Pt 1):670-673. (Retrospective review; 129 patients)
52. Valentini RP, Lakshmanan Y. Nephrolithiasis in children. Adv Chronic Kidney Dis. 2011;18(5):370-375. (Review)
53. Walther PC, Lamm D, Kaplan GW. Pediatric urolithiases: a ten-year review. Pediatrics. 1980;65(6):1068-1072. (Retrospective review; 61 patients)
54. Milliner DS, Murphy ME. Urolithiasis in pediatric patients. Mayo Clin Proc. 1993;68(3):241-248. (Retrospective study; 221 patients)
55. Pumberger W, Gindl K, Amann G, et al. Polypoid fibrohaemangioma of the kidney in a child with gross haematuria. Scand J Urol Nephrol. 1999;33(5):344-346. (Case report; 1 patient)
56. Jahn H, Nissen HM. Haemangioma of the urinary tract: review of the literature. Br J Urol. 1991;68(2):113-117. (Review)
57. Cheng L, Nascimento AG, Neumann RM, et al. Hemangioma of the urinary bladder. Cancer. 1999;86(3):498-504. (Retrospective review; 19 patients)
58. Ashley RA, Figueroa TE. Gross hematuria in a 3-year-old girl caused by a large isolated bladder hemangioma. Urology. 2010;76(4):952-954. (Case report; 1 patients)
59. Dell KM. The spectrum of polycystic kidney disease in children. Adv Chronic Kidney Dis. 2011;18(5):339-347. (Review)
60. Goldner AP, Mayron R, Ruiz E. Are urine dipsticks reliable indicators of hematuria in blunt trauma patients? Ann Emerg Med. 1985;14(6):580-582. (Retrospective review; 185 patients)
61. Lieu TA, Fleisher GR, Mahboubi S, et al. Hematuria and clinical findings as indications for intravenous pyelography in pediatric blunt renal trauma. Pediatrics. 1988;82(2):216-222. (Retrospective study; 78 patients)
62. Morey AF, Bruce JE, McAninch JW. Efficacy of radiographic imaging in pediatric blunt renal trauma. J Urol. 1996;156(6):2014-2018. (Retrospective record review; 180 patients)
63. Hynick NH, Brennan M, Schmit P, et al. Identification of blunt abdominal injuries in children. J Trauma Acute Care Surg. 2014;76(1):95-100. (Retrospective study; 571 patients)
64. * Thorp AW, Young TP, Brown L. Test characteristics of urinalysis to predict urologic injury in children. West J Emerg Med. 2011;12(2):168-172. (Retrospective record review; 502 patients)
65. Sears DA. The morbidity of sickle cell trait: a review of the literature. Am J Med. 1978;64(6):1021-1036. (Review)
66. Heller P, Best WR, Nelson RB, et al. Clinical implications of sickle-cell trait and glucose-6-phosphate dehydrogenase deficiency in hospitalized black male patients. N Engl J Med. 1979;300(18):1001-1005. (Cooperative study; 65,154 patients)
67. Eckert DE, Jonutis AJ, Davidson AJ. The incidence and manifestations of urographic papillary abnormalities in patients with S hemoglobinopathies. Radiology. 1974;113(1):59-63. (Review)
68. Scheinman JI. Sickle cell disease and the kidney. Nat Clin Pract Nephrol. 2009;5(2):78-88. (Review)
69. Okada M, Tsuzuki K, Ito S. Diagnosis of the nutcracker phenomenon using two-dimensional ultrasonography. Clin Nephrol. 1998;49(1):35-40. (Prospective study; 125 patients)
70. Kim SH, Cho SW, Kim HD, et al. Nutcracker syndrom e: diagnosis with Doppler US. Radiology. 1996;198(1):93-97. (Prospective study; 34 patients)
71. Shin JI, Park JM, Lee JS, et al. Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children with hematuria. Eur J Pediatr. 2007;166(5):399-404. (Prospective study; 216 patients)
72. Jones GR, Newhouse I. Sport-related hematuria: a review. Clin J Sport Med. 1997;7(2):119-125. (Review)
73. Kaplan BS, Meyers K. Images in clinical medicine. Schistosoma haematobium. N Engl J Med. 2000;343(15):1085. (Case report)
74. Vijayakumar M, Nammalwar BR. Diagnostic approach to a child with hematuria. Indian Pediatr. 1998;35(6):525-532. (Review)
75. Kincaid-Smith P, Fairley K. The investigation of hematuria. Semin Nephrol. 2005;25(3):127-135. (Review)
76. Stapleton FB. Morphology of urinary red blood cells: a simple guide in localizing the site of hematuria. Pediatr Clin North Am. 1987;34(3):561-569. (Review)
77. Mehta K, Tirthani D, Ali U. Urinary red cell morphology to detect site of hematuria. Indian Pediatr. 1994;31(9):1039-1045. (Prospective study; 87 patients)
78. Hockberger RS, Schwartz B, Connor J. Hematuria induced by urethral catheterization. Ann Emerg Med. 1987;16(5):550- 552. (Prospective study; 93 patients)
79. Suresh S, Mahajan P, Kamat D. Emergency management of pediatric hypertension. Clin Pediatr (Phila). 2005;44(9):739- 745. (Review)
80. Halachmi S, Kakiashvili D, Meretyk S. A review on hematuria in children. ScientificWorldJournal. 2006;6:311-317. (Review)