Douglas W. Storm, MD, FAAP, FACS
Christopher S. Cooper, MD, FAAP, FACS
BASICS
DESCRIPTION
• Hematuria can be macroscopic or microscopic
– Macroscopic: Grossly red/pink-tinged urine
– Microscopic: >5–10 RBC/hpf
– Common pediatric urology referral
– Approach is different in children compared to adults
Low risk of malignancy as cause in children
Medical causes more frequent than surgical
EPIDEMIOLOGY
Incidence
• Microscopic hematuria more frequently encounte-red than gross hematuria (1,2)[A]
• Microscopic hematuria
– 0.41% (41 in 1,000 pediatric visits)
– 0.32% school-aged girls
– 0.14% school-aged boys
• Macroscopic hematuria
– 0.13% (1.3 in 1,000 pediatric visits)
– 80% of cases involve males; 20% females
Prevalence
Exact prevalence is unknown
RISK FACTORS
• Alport syndrome
• Anaphylactoid purpura
• Benign familial hematuria
• Dysfunctional voiding
• Glomerular bleeding
• Glomerulonephritis (GN)
• Hemophilia
• Henoch–Schönlein purpura (HSP)
• Genitourinary anatomic anomaly
• Kidney stones
• Medications
• Recent upper respiratory illness
• Recent strep throat
• Renal papillary necrosis
• Sexual abuse
• Sickle cell disease or trait
• Systemic lupus erythematosus (SLE)
• Trauma
• UTI
• Vigorous exercise
Genetics
• Benign familial hematuria: Autosomal dominant
• Sickle cell anemia: Autosomal recessive
• Alport syndrome: X-linked
PATHOPHYSIOLOGY
• Depends on source of the bleeding:
– Glomerular source (most common)
– Renal tubular source
– Interstitial source
– Vascular source
– Urinary tract
ASSOCIATED CONDITIONS
Depends on the bleeding source
GENERAL PREVENTION
Must understand the source of the bleeding and tailor prevention accordingly
DIAGNOSIS
HISTORY
• Age of child and timing of onset:
– Poststreptococcal GN occurs 14–28 days after the sore throat
– IgA nephropathy hematuria occurs at the time of or shortly after the respiratory illness
– HSP hematuria occurs 1–3 mo after the rash
• Characterize the pattern of hematuria
– Gross pink/red urine suggests a urologic cause
Initial or terminal hematuria suggests lower urinary tract source
Total hematuria suggests upper tract source
Idiopathic urethrorrhagia seen in prepubertal boys with blood spotting at the end of urinary stream
– Gross brown, tea-colored, or cola-colored suggests glomerular origin
– Microscopic suggests nephrologic cause
• Any precipitating events
– Recent viral illness, strep throat, skin rash
– Trauma, strenuous exercise, foreign bodies, sexual abuse, or bleeding/coagulation disorders
• Associated lower urinary tract symptoms (urgency, frequency, dysuria) and/or flank and abdominal pain suggests UTI, stone disease, or dysfunctional voiding component
• Family history of renal disorders, stones, end-stage renal disease, neurosensory hearing loss, HTN, or coagulopathy
• Current medications
PHYSICAL EXAM
• Blood pressure (BP)
– High BP is suggestive of glomerular disease, especially when accompanied with edema
• Presence of fever and costovertebral angle (CVA) tenderness suggests stone and/or pyelonephritis
• Presence of palpable abdominal or flank mass, bruit, or abdominal tenderness
• Skin rashes and arthritis may suggest HSP and SLE
• Hearing loss suggests Alport disease
• Examine the genitalia for meatal stenosis, urethral prolapse, ureterocele, trauma, sexual abuse
• Edema suggestive of nephrotic syndrome
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Microscopic hematuria considered clinically significant if >5–10 RBC/hpf
– Recommend that 2 of 3 urinalyses show microscopic hematuria over 2–3 wk before work-up initiated (1,2)[A]
False-negative results occur with high urine specific gravity or with high ascorbic acid concentration
False-positive results occur in presence of myoglobin, medications (eg, rifampin, pyridium, etc.), bile pigments, and oxidizing agents (eg, household bleaches)
• Urinalysis
– Proteinuria
If 1+– or 2+ child should be evaluated for postural proteinuria
2+ or greater proteinuria child should be evaluated for glomerulonephritis and nephrotic syndrome
– RBC casts are highly specific for glomerulonephritis
– Dysmorphic RBCs predict glomerular bleeding with a sensitivity of 93–95% and a specificity of 95–100%
– WBCs, bacteria, leukocyte esterase, nitrates suggest UTI
Recommend urine culture to verify UTI and identify bacteria causing the infection
• Other blood tests:
– Serum creatinine, BUN, electrolytes (if renal insufficiency noted)
– Complete blood count CBC)
– antistreptolysin O titer/streptozyme panel (indicative of poststreptococcal GM)
– C3/C4 levels (may be lowered in cases of SLE and GN)
– plasma IgA levels (may be increased with IgA nephritis and HSP)
• Other urine tests:
– urine calcium to creatinine ratio (varies by age, but generally <0.18; if >0.18 suggests high 24-hr excretion of calcium >4 mg/kg/d)
• Other lab tests:
– throat culture (to rule out strep throat)
Imaging
• Renal and bladder sonography
– Evaluates for renal parenchymal disorders, stones, tumors, renal artery stenosis, and anatomic abnormalities
• Voiding cystourethrogram (VCUG)
– Not routinely performed in work-up of hematuria
– May be done if hematuria is felt to be in conjunction with febrile UTI, concern for urethral obstruction, or other lower urinary tract abnormalities
• CT
– Selectively used in pediatrics secondary to radiation exposure
– May be used to evaluate for stone disease or anatomic abnormality or after recent trauma
Diagnostic Procedures/Surgery
• Renal biopsy
– Heavy proteinuria and worsening renal function are the main indications for biopsy. Only performed if the results will alter therapy.
• Cystoscopy
– Rarely performed in children
– Performed if bleeding source thought to originate from the lower urinary tract
– May inspect efflux of urine from each ureteral orifice to lateralize source of bleeding
– May perform retrograde ureteropyelogram to look for upper tract source (eg, fibroepithelial polyp)
• Hearing test
– Alport syndrome
Pathologic Findings
Dependent on the cause of the bleeding
DIFFERENTIAL DIAGNOSIS
• Divided into categories, based on the source of the bleeding
– Glomerular sources
– Interstitial and tubular sources
– Urinary tract source
– Vascular source
• Glomerular source
– IgA nephropathy or Berger disease (recurrent gross, painless hematuria, often following a mild fever, upper respiratory illness, viral illness, or exercise)
– Benign familial hematuria (usually microscopic hematuria also found in parent without hearing loss or renal insufficiency)
– Alport syndrome (usually microscopic hematuria, proteinuria, progressive renal insufficiency, high-frequency hearing loss, family history of renal disease)
– Acute poststreptococcal glomerulonephritis (PSGN) (usually acute onset edema, tea-colored urine, history of antecedent illness 2–4 wk prior, elevated BP, urinalysis with RBC casts, and proteinuria)
– Membranoproliferative glomerulonephritis
– SLE
– Rapidly progressive glomerulonephritis (pediatric nephrology emergency, presents with signs and symptoms similar to PSGN, renal function though shows renal insufficiency, may progress to end-stage renal disease in a few weeks)
– Henoch–Schönlein purpura (rash on dependent parts of the body, renal manifestations may include: No involvement, HTN, active glomerulonephritis, nephrotic syndrome, and acute renal failure)
– Goodpasture syndrome (pulmonary hemorrhage associated with severe and progressive glomerulonephritis)
• Interstitial and tubular source
– Acute pyelonephritis
– Renal tuberculosis
– Sickle cell disease or trait
– Acute interstitial nephritis
– Nephrocalcinosis
– Metabolic (eg, Fabry disease)
– Nephrotoxins (eg, analgesics, NSAIDs)
– Renal cystic disease
– Acute tubular necrosis
• Urinary tract source
– Dysfunctional voiding and elimination
– Papillary necrosis
– HIV, hepatitis
– Infestations (eg, schistosomiasis)
– Nephrolithiasis
– Anatomic abnormality (eg, ureteropelvic junction obstruction, fibroepithelial polyp)
– Hemorrhagic cystitis (eg, viral, chemical, radiation)
– UTI
– Urethritis
– Hypercalciuria
– Tumor
– Drug-induced cystitis (eg, chemotherapy, antibiotics, Coumadin, etc.)
– Menstruation
– Foreign bodies (eg, urinary catheter)
– Exercise
– Trauma
• Vascular source
– Trauma
– Sickle cell disease/trait
– Renal vein thrombosis
– Renal artery thrombosis (20% of gross hematuria in 1st months of life)
– Arteriovenous malformation
– Nutcracker syndrome
– Vasculitis (eg, C3 arteriolar deposition)
– Coagulopathy
– Thrombocytopenia
TREATMENT
GENERAL MEASURES
• Establish diagnosis and treat any underlying medical problems causing the hematuria
• Prompt evaluation must be provided to a child with any of the following in addition to the hematuria (1,2)[A]
– HTN
– Edema
– Oliguria
– Significant proteinuria (2+ or greater)
– RBC casts
MEDICATION
Based on underlying cause of hematuria
OTHER PROCEDURES
Based on clinical diagnosis and etiology of the hematuria
ADDITIONAL TREATMENT
Additional Therapies
Based on clinical diagnosis and etiology of the hematuria
Complementary & Alternative Therapies
Based on clinical diagnosis and etiology of the hematuria
ONGOING CARE
PROGNOSIS
Based on underlying cause of the hematuria (3)
COMPLICATIONS
Based on the underlying cause of the hematuria and any interventions delivered
FOLLOW-UP
Patient Monitoring
• Current recommendation of American Academy of Pediatrics is screening urinalysis at age 5 yr
• Annual measurements of height, weight, and BP measurements after age 3 yr
Patient Resources
• http://www.uptodate.com/contents/evaluation-of-microscopic-hematuria-in-children
• http://www.uptodate.com/contents/evaluation-of-gross-hematuria-in-children
• www.chop.edu/healthinfo/hematuria.html
• http://www.childrenshospital.org/az/Site1000/mainpageS1000P1.html
REFERENCES
1. Meyers KE. Evaluation of hematuria in children. Urol Clin North Am. 2004;31:559–573.
2. Patel HP, Bissler JJ. Hematuria in children. Pediatr Clin North Am. 2001;48:1519–1537.
3. AAP Committee on Practice and Ambulatory Medicine. Recommendations for preventive pediatric health care. Pediatrics. 2000;105:645–646.
ADDITIONAL READING
• Feld LG, Waz WR, Pérez LM, et al. Hematuria. An integrated medical and surgical approach. Pediatr Clin North Am. 1997;44:1191–1210.
• Quigley R. Evaluation of hematuria and proteinuria: How should a pediatrician proceed? Curr Opin Pediatr. 2008;20:140–44.
See Also (Topic, Algorithm, Media)
• Cystitis, Hemorrhagic (Infectious, Noninfectious, Radiation)
• Hematuria, Gross and Microscopic, Pediatric Images 
• Hematuria, Pediatric Macroscopic (Gross) Algorithm 
• Hematuria, Pediatric Microscopic/Isolated Asymptomatic
• Hematuria, Gross and Microscopic, Adult
• Hematuria-Loin Pain Syndrome
• Urine, Abnormal Color
CODES
ICD9
• 599.0 Urinary tract infection, site not specified
• 599.71 Gross hematuria
• 599.72 Microscopic hematuria
ICD10
• N39.0 Urinary tract infection, site not specified
• R31.0 Gross hematuria
• R31.2 Other microscopic hematuria
CLINICAL/SURGICAL PEARLS
• Prompt evaluation must be provided to a child with any of the following in addition to the hematuria:
– HTN, edema, oliguria, significant proteinuria, RBC casts
– Unstable BP, renal insufficiency, fevers