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Evaluation of gross hematuria in children

Evaluation of gross hematuria in children
Literature review current through: Jan 2024.
This topic last updated: Feb 06, 2023.

INTRODUCTION — Gross hematuria is defined by the presence of an increased number of red blood cells (RBCs) in the urine that is visible to the naked eye. Although an uncommon occurrence in children, it is nevertheless a disturbing finding for both the affected child and his/her family.

The causes and evaluation of gross hematuria in children will be reviewed here. The evaluation of children with microscopic hematuria is discussed separately. (See "Evaluation of microscopic hematuria in children".)

CONFIRMATION — Gross hematuria is suspected when red or brown urine is present. However, red or brown urine can be due to causes other than blood including the following (table 1):

Pigments from drugs (eg, phenazopyridine, rifampicin) or foods (eg, beets)

Metabolites associated with other clinical conditions (eg, porphyria)

Free hemoglobin or myoglobin

Thus, the initial step in the evaluation of patients with red urine is to establish whether or not the urine discoloration is due to blood or another substance. This is accomplished by the following two procedures:

Urinary dipstick test for blood – The reagent strip that detects blood utilizes hydrogen peroxide, which catalyzes a chemical reaction between hemoglobin (or myoglobin) and the chromogen tetramethylbenzidine. If the urinary dipstick test is positive for blood, the likely cause of the red/brown pigmentation is blood, or free hemoglobin or myoglobin. A negative test eliminates these etiologies as the cause of urinary discoloration.

Urine centrifugation – If after centrifugation of the urine specimen the sediment is red/brown, then the etiology is most likely blood (algorithm 1). If the supernatant is red/brown and the sediment is not discolored, then the red/brown urine is not due to blood but to another substance, such as free hemoglobin or myoglobin. Microscopic examination of the sediment should confirm the presence of red blood cells (RBCs). (See "Urinalysis in the diagnosis of kidney disease", section on 'Red to brown urine'.)

In patients with gross hematuria, the color change does not necessarily reflect the degree of blood loss, since as little as 1 mL of blood per liter of urine can induce a visible color change.

ETIOLOGY — The most commonly identified etiologies for gross hematuria in children include urinary tract infection (UTI), irritation of the meatus or perineum, and trauma [1,2]. Other less common causes include nephrolithiasis, sickle cell disease/trait, coagulopathy, glomerular disease including postinfectious glomerulonephritis and immunoglobulin A (IgA) nephropathy, malignancies (eg, Wilms tumor and rarely, transitional cell carcinoma of the bladder), and drug-induced hemorrhagic cystitis, such as is seen with cyclophosphamide [1]. Post-micturition urethral bleeding, a benign condition, may also be seen in infant boys with resolution by one year of age in most cases [3].

The relative frequency of the known causes of gross hematuria in children varies depending upon the clinical setting. This is illustrated by several case series of children with gross hematuria who presented to three different clinical settings (ie, a pediatric emergency department [1], a pediatric urology referral service [4], or a pediatric nephrology referral service [5]).

In a 1977 two-year retrospective review of 150 patients presenting to a tertiary pediatric emergency center with gross hematuria, either documented (n = 39) or suspected (n = 35) UTI was the underlying diagnosis in half of the patients [1]. Other causes included perineal or urethral irritation (18 percent), trauma (7 percent), acute nephritis (4 percent), coagulopathy (3 percent), and stone (2 percent). In 10 percent of patients, no etiology was found.

In a 10-year retrospective review of 342 children who presented with gross hematuria to a pediatric urologic center in the United States between 1994 and 2004 [4], the causes of gross hematuria and their frequency included urethral irritation or trauma (15 percent), UTI (14 percent), underlying congenital anomalies such as vesicoureteral reflux (VUR), posterior urethral valves (PUV), or ureteropelvic junction obstruction (UPJO) (13 percent), nephrolithiasis (5 percent), and malignancy (1 percent). In 35 percent of the patients, no cause could be determined. In addition, bladder or urethral abnormalities were seen in 76 of 136 patients who underwent cystoscopy including posterior urethritis (n = 25), cystitis (n = 25), bladder trabeculation (n = 7), and urethral stricture (n = 6).

In this urologic case series, there were no cases of glomerular disease, which is most likely due to referral bias. This was illustrated by the third retrospective case series from a pediatric nephrology referral center that demonstrated a greater proportion of cases due to glomerular disease compared with both of the two previous studies [5]. In this review, results were based upon 82 of 100 patients with completed evaluation. The following findings were noted:

A glomerular cause was identified in 24 patients (29 percent). The two most common diagnoses were IgA nephropathy (n = 13) and Alport syndrome (n = 6). (See "IgA nephropathy: Clinical features and diagnosis" and "Genetics, pathogenesis, and pathology of Alport syndrome (hereditary nephritis)".)

Nonglomerular etiology was established in 30 patients (37 percent). The most common diagnoses were hypercalciuria (n = 9), urethral irritation or trauma (n = 8), and hemorrhagic cystitis (n = 7).

No cause was found in the remaining 28 patients (34 percent). In 26 of these patients, the hematuria was attributed to a nonglomerular source.

In the two referral-based studies, boys were at a higher risk for gross hematuria than girls because of their increased susceptibility to trauma of the urethral meatus [4,5]. However, in the first study, there was no gender difference. The increased prevalence of female patients with gross hematuria due to urinary tract infections seen in the emergency department setting appears to have offset the predominance of boys with recurrent gross hematuria due to trauma, resulting in the reported equal distribution of boys and girls [1].

EVALUATION — The majority of children who present with gross hematuria have an easily recognizable and apparent cause [1]. The clinician generally is able to establish the underlying etiology by a complete history, physical examination, and urinalysis (algorithm 2).

Historical clues — There are often clues from the history that point toward a specific diagnosis.

Recent vigorous exercise or trauma. (See "Exercise-induced hematuria".)

History of new onset of incontinence, dysuria, frequency, or urgency suggests urinary tract infection (UTI) as a possible cause. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Older children'.)

History of unilateral flank pain that may radiate to the groin suggests obstruction caused by a calculus or blood clot. In comparison, flank pain without radiation but with fever, dysuria, and frequency and/or urgency is suggestive of acute pyelonephritis. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Older children'.)

The timing of hematuria during micturition may suggest an etiology. As an example, initial hematuria (onset of urination) usually suggests urethral bleeding; continuous bleeding throughout urination may occur from bleeding in the bladder, ureter or kidneys; and terminal bleeding (at the end of urination) is indicative of bladder disease.

The color of urine may distinguish glomerular bleeding from extraglomerular bleeding. Glomerulonephritis is associated with brown urine. Bleeding from the lower urinary tract is suggested by pink or red urine and may be accompanied by blood clots. (See "Etiology and evaluation of hematuria in adults", section on 'Glomerular versus nonglomerular bleeding' and 'Urinalysis' below.)

A history of pharyngitis or impetigo (two or three weeks prior to onset of hematuria) suggests poststreptococcal glomerulonephritis, although a recent upper respiratory (one or two days prior to onset of hematuria) infection can be associated with immunoglobulin A (IgA) nephropathy. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

A history of predisposing clinical conditions such as sickle cell disease or trait [6], or coagulopathy such as severe hemophilia.

Exposure to medications that can cause hemorrhagic cystitis (such as cyclophosphamide), eosinophilic cystitis (nonsteroidal anti-inflammatory drug or antihistamines) [7-9], or interstitial nephritis (such as nonsteroidal anti-inflammatory drug [ibuprofen] or penicillins, although hematuria is not typically the central manifestation in such patients). (See "Clinical manifestations and diagnosis of acute interstitial nephritis", section on 'Drugs'.)

Physical examination — The physical examination should include

Measurement of blood pressure (BP) – Elevated BP may be seen in patients with glomerular disease and low BP in patients with significant bleeding due to trauma.

Assessment for edema and recent weight gain – These findings may be seen in patients with glomerular disease due to fluid retention or patients with impaired water excretion. (See "Pathophysiology and etiology of edema in children", section on 'Acute glomerulonephritis' and "Pathophysiology and etiology of edema in children", section on 'Nephrotic syndrome' and "Pathophysiology and etiology of edema in children", section on 'Renal failure'.)

Skin examination for rash or purpura that suggests systemic condition associated with glomerular disease (eg, systemic lupus erythematous [SLE] or IgA vasculitis [Henoch-Schönlein purpura]). (See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Mucocutaneous' and "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Skin manifestations'.)

Examination of the genitals (looking for penile urethral meatal erosion or female introitus pathology).

Evaluation for abdominal discomfort or masses (eg, Wilms tumor).

Urinalysis — Examination of the urine may suggest an underlying etiology and potential site of bleeding (glomerular versus extraglomerular).

Glomerular bleeding – Signs of glomerular bleeding include red cell casts (pathognomonic for glomerular disease) (picture 1), red cells having a dysmorphic appearance, and brown, cola-colored urine (table 2). In a first morning urinary sample, protein excretion greater than 100 mg/m2 at a time when there is no gross bleeding is also indicative of glomerular source of blood. Although helpful if present, the absence of these findings does not exclude glomerular disease.

Morphologic study of urinary red blood cells (RBCs), particularly with a phase-contrast microscope, may be helpful in distinguishing glomerular from nonglomerular bleeding. The presence of more than 30 percent dysmorphic RBCs or of more than 5 percent of a specific form named an "acanthocyte" is highly suggestive of glomerular hematuria (picture 2 and picture 3). However, confident identification of such cells requires expertise in urinalysis. (See "Etiology and evaluation of hematuria in adults", section on 'Glomerular versus nonglomerular bleeding'.)

Nonglomerular bleeding – In nonglomerular hematuria, the urine is typically red or pink in color. Microscopic examination demonstrates urinary RBCs with a uniform normal size and shape (picture 4). Blood clots virtually never occur with glomerular disease and are indicative of an extraglomerular source of hematuria.

The procedures for obtaining and processing urine samples in children are reviewed separately. (See "Urine collection techniques in infants and children with suspected urinary tract infection".)

Further evaluation

Symptomatic hematuria — In patients who have symptomatic hematuria, further evaluation is guided by their clinical symptoms, history, physical examination, and urinalysis (algorithm 2).

Trauma history – Obtain a computed tomography (CT) scan of the abdomen and pelvis to determine the source of blood.

Signs or symptoms of UTI – Additional findings on urinalysis suggestive of a UTI include positive dipstick tests for leukocyte esterase and/or nitrite, more than five white blood cells per high-power field (spun urine), and the presence of bacteria on a Gram stain of unspun urine.

An appropriately collected urine culture is obtained. If the culture is positive, treat appropriately and repeat urinalysis after the infection has cleared.

Adenovirus should be considered as a potential etiology if urinary symptoms and urinalysis are suggestive of infection, but the culture is negative [10,11].

Signs or symptoms of perineal/meatal irritation – Supportive care and reassurance.

Signs or symptoms of nephrolithiasis – The evaluation begins with imaging. Renal ultrasonography is the preferred modality in children. Abdominal plain films may be useful in identification of radiopaque stones but will miss radiolucent uric acid stones, small stones, or stones overlying bony structures, and will not detect obstruction.

Spiral CT scan is the most sensitive imaging modality. However, because of concerns related to radiation exposure, it is not typically the initial test in young children as it is in adolescents and adults. Consultation with radiology may be warranted in younger children to determine the risk-to-benefit ratio of the test. (See "Kidney stones in children: Clinical features and diagnosis", section on 'Imaging'.)

Signs or symptoms suggestive of glomerular disease – Manifestations such as proteinuria, RBC casts, edema, and hypertension suggest a glomerular source for the hematuria. The evaluation includes serum creatinine, complete blood count, complement component 3 (C3), complement component 4 (C4), and serum albumin. Other tests to consider based upon the history and the physical examination include antistreptolysin O (ASO) titer and/or streptozyme testing to detect poststreptococcal glomerulonephritis, and antinuclear antibody testing to detect lupus nephritis. Such patients should be referred to a pediatric nephrologist (or a clinician with expertise in the care of children with renal disease).

Asymptomatic hematuria — Thorough diagnostic evaluation of children with asymptomatic gross hematuria is often warranted and generally leads to a diagnosis. This was illustrated in a retrospective review of 228 patients who presented to a single center for evaluation of asymptomatic gross hematuria [12]. Evaluation included complete blood count, urinalysis, serum creatinine, serum C3, ultrasonography or intravenous pyelography, and renal biopsy in some cases. Etiologies for gross hematuria included the following:

No identifiable cause – 36 percent

Hypercalciuria – 22 percent

IgA nephropathy – 16 percent

Poststreptococcal glomerulonephritis – 7 percent

Other glomerulopathies including thin basement membrane (TBM) disease – 2 percent

Congenital anomalies (eg, ureteropelvic junction obstruction [UPJO] or renal dysplasia) – 2 percent

Sickle cell trait – 1 percent

In addition, left renal vein compression between the aorta and proximal superior mesenteric artery, referred to as "nutcracker syndrome," has been suggested as a cause of gross and microscopic hematuria in children that is usually asymptomatic, but may be associated with left flank pain [13,14]. Nutcracker syndrome is detected by Doppler ultrasonographic assessment of left renal vein diameter and peak velocity or computed tomography (image 1 and image 2) [13,15].

The frequency of hematuria due to nutcracker syndrome in children appears to be highest in Asia, with the diagnosis rarely entertained in North America. This was illustrated in a Japanese case series of 85 children with hematuria without nephritis, nephrolithiasis, or tumor. Doppler ultrasonographic findings were consistent with a diagnosis of nutcracker syndrome in 21 of 23 children with gross hematuria and 17 of 52 patients with microscopic hematuria [13]. Similar findings were noted in a report from Korea of 216 children with isolated microscopic or gross hematuria [14]. Doppler ultrasonographic results were consistent with nutcracker syndrome in 33 percent.

Nutcracker syndrome can also cause orthostatic proteinuria in children. (See "Orthostatic (postural) proteinuria", section on 'Left renal vein entrapment'.)

In children with asymptomatic gross hematuria, we suggest using the following evaluation:

Urinalysis including microscopic examination to determine if red cell casts (eg, glomerular disease) or pyuria (eg, infection) are present. The protein dipstick will not be reliably detect proteinuria due to the large number of RBCs.

Measurement of serum creatinine to identify renal impairment, which may occur with acute glomerulonephritis

A low level of C3 would be consistent with a diagnosis of poststreptococcal glomerulonephritis or lupus nephritis is suspected.

Urine culture to diagnose infection.

Measurement of urine calcium/creatinine to detect possible hypercalciuria, defined as a urine calcium/creatinine ratio >0.2 (mg/mg).

Testing parents and siblings for hematuria (possible TBM disease or hereditary nephritis, although gross hematuria is not a common presentation).

Consider renal and bladder ultrasound with Doppler study to detect congenital abnormalities of the kidney or urinary tract (CAKUT), tumor, or nutcracker syndrome. (See "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)".)

If there is a consideration of sickle cell trait or disease, a hemoglobin electrophoresis should be obtained. (See "Sickle cell disease effects on the kidney".)

If no diagnosis is made and hematuria persists, the patient should be referred to a pediatric nephrologist or a clinician with expertise in the care of children with renal disease. Patient referral is also recommended if there is evidence of significant renal disease (ie, hypertension, elevated serum creatinine level, proteinuria, or evidence of glomerular bleeding, such as red cell casts).

Cystoscopy — Cystoscopy is rarely indicated for hematuria in children. It should be reserved for the rare child with a bladder mass noted on ultrasound, persistent symptoms suggestive of inflammatory cystitis, or those with urethral abnormalities due to trauma.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pediatric hematuria".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Blood in the urine (hematuria) in children (The Basics)")

Beyond the Basics topic (see "Patient education: Blood in the urine (hematuria) in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Confirmation – Gross hematuria is suspected when red or brown urine is present. However, red or brown urine may be due to causes other than blood. Thus, gross hematuria must be distinguished from other causes of red/brown urine by a positive urinary dipstick for blood and a red/brown urine sediment (algorithm 1). Other causes include free hemoglobin or myoglobin, pigments from drugs (eg, phenazopyridine) or foods (eg, beets), or metabolites associated with other clinical conditions (eg, porphyria). (See "Urinalysis in the diagnosis of kidney disease", section on 'Red to brown urine' and 'Confirmation' above.)

Etiology – Urinary tract infection (UTI), irritation to the meatus or perineum, and trauma are the most common causes of gross hematuria in children [1,2]. Other less common causes include nephrolithiasis, sickle cell disease/trait, coagulopathy, glomerular disease including postinfectious glomerulonephritis and immunoglobulin A (IgA) nephropathy, malignancies (eg, Wilms tumor), and drug-induced hemorrhagic cystitis (eg, cyclophosphamide). (See 'Etiology' above.)

Evaluation

Symptomatic hematuria – The majority of symptomatic children who present with gross hematuria have an easily recognizable and apparent cause generally detected by an initial evaluation that includes a complete history, physical examination, and urinalysis (algorithm 2). Further testing is guided by the clinical findings of the initial evaluation. (See 'Symptomatic hematuria' above.)

Asymptomatic hematuria – Diagnostic evaluation of asymptomatic patients usually determines an underlying cause of hematuria and includes urinalysis, urine culture, testing family members for hematuria, ultrasonography of the kidneys and bladder, and measurements of serum creatinine, serum complement component 3 (C3), and urine calcium/creatinine. (See 'Asymptomatic hematuria' above.)

  1. Ingelfinger JR, Davis AE, Grupe WE. Frequency and etiology of gross hematuria in a general pediatric setting. Pediatrics 1977; 59:557.
  2. Patel HP, Bissler JJ. Hematuria in children. Pediatr Clin North Am 2001; 48:1519.
  3. Walker BR, Ellison ED, Snow BW, Cartwright PC. The natural history of idiopathic urethrorrhagia in boys. J Urol 2001; 166:231.
  4. Greenfield SP, Williot P, Kaplan D. Gross hematuria in children: a ten-year review. Urology 2007; 69:166.
  5. Youn T, Trachtman H, Gauthier B. Clinical spectrum of gross hematuria in pediatric patients. Clin Pediatr (Phila) 2006; 45:135.
  6. Pham PT, Pham PC, Wilkinson AH, Lew SQ. Renal abnormalities in sickle cell disease. Kidney Int 2000; 57:1.
  7. Taktak A, Acar B, Gür G, et al. An unusual cause of gross hematuria: questions and answers. Pediatr Nephrol 2015; 30:767, 769.
  8. Hwang EC, Kwon DD, Kim CJ, et al. Eosinophilic cystitis causing spontaneous rupture of the urinary bladder in a child. Int J Urol 2006; 13:449.
  9. van den Ouden D. Diagnosis and management of eosinophilic cystitis: a pooled analysis of 135 cases. Eur Urol 2000; 37:386.
  10. Badenas C, Praga M, Tazón B, et al. Mutations in theCOL4A4 and COL4A3 genes cause familial benign hematuria. J Am Soc Nephrol 2002; 13:1248.
  11. Buzza M, Wilson D, Savige J. Segregation of hematuria in thin basement membrane disease with haplotypes at the loci for Alport syndrome. Kidney Int 2001; 59:1670.
  12. Bergstein J, Leiser J, Andreoli S. The clinical significance of asymptomatic gross and microscopic hematuria in children. Arch Pediatr Adolesc Med 2005; 159:353.
  13. Okada M, Tsuzuki K, Ito S. Diagnosis of the nutcracker phenomenon using two-dimensional ultrasonography. Clin Nephrol 1998; 49:35.
  14. Shin JI, Park JM, Lee JS, Kim MJ. Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children with hematuria. Eur J Pediatr 2007; 166:399.
  15. Vianello FA, Mazzoni MB, Peeters GG, et al. Micro- and macroscopic hematuria caused by renal vein entrapment: systematic review of the literature. Pediatr Nephrol 2016; 31:175.
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