What Causes Gross Hematuria?

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Patient Presentation
A 14-year-old African-american female came to emergency room after having an episode of painless gross hematuria. She had been otherwise well and had bright red urine in the toilet. She had no burning, pruritis, or change in frequency of urination.
She had been drinking, voiding and defecating normally previously.
She was well with no recent illnesses, her last menstrual period was 2 weeks ago and was normal. She denies sexual activity, trauma, and easy bruising or bleeding.
She had no medication or illicit drug use except acetaminophen which she took several days before this episode. She was a cross-country runner and 2 weeks previously began her pre-season training. She had a normal physical examination about 1 month ago.
The past medical history was negative including sickle cell trait or disease or other hemoglobinopathies.
The family history was positive for arthritis and sickle cell trait. There was no kidney disease, hearing problems, urolithiasis, gynecologic or other rheumatologic diseases.
The review of systems was negative.
The pertinent physical exam revealed a healthy female with normal vital signs including a blood pressure of 112/74, and weight and height at 25-50%. She had no edema noted. Skin examination revealed no rashes and a few bruises on her lower legs. There were anterior cervical and inguinal shoddy adenopathy.
Genitourinary examination revealed a Tanner Stage V female with normal genitalia. No evidence of perineal irritation, trauma or blood was seen. Her external rectal examination was also normal. The rest of her examination was normal.
The laboratory evaluation included a complete blood count with a hemoglobin of 13.2 g/dl, hematocrit of 38% , white blood cells of 8.4 1000/mm2 and platelets of 1.75 x 1000/mm2 with a normal smear.
A urinalysis revealed 1.20 specific gravity, 6.5 pH, 4+ blood, 1+ leukocyte esterase and +1 protein on dipstick. Microscopic examination revealed too numerous to count red blood cells, 1-2 white blood cells, and rare fine granular casts.
Her serum calcium, total protein and electrolyes were normal with a blood urea nitrogen of 12 mg/dl and a creatinine of 0.8 mg/dl.
Urine culture and Anti-streptolysin O titre were sent.
The diagnosis of painless gross hematuria of unknown cause was made at that time, but the physician was considering idiopathic, post-infectious glomerulonephritis and exercise as the most likely causes. The patient was to follow-up with her regular physician within the week and sooner if the hematuria returned. She was told that she most likely needed further tests such as a urine collection, additional urinalayses and possibly a renal ultrasound.

Discussion
Hematuria is either gross or microscopic (> 5 red blood cells per high power field on a centrifuged urine sample). It is a common sign and symptom in healthy children and those with underlying renal disease. It is estimated that ~1-2% of school age children have hematuria on at least one urine sample and 0.5% will continue to have it in two of three samples.

Gross hematuria is much less common than microscopic hematuria and most pediatric nephrologists believe it deserves a complete work-up.
What is included in a complete workup varies by the source. Commonly cited laboratory testing includes:

  • Urinalysis
  • Urine culture – infection
  • Blood urea nitrogen and creatinine – renal function
  • Electrolytes – hyperkalemia, acidosis, etc.
  • Complete blood count – hemoglobinopathy, coagulopathy, chronic disease, tumor, hemolytic uremia syndrome, etc.
  • Serum total protein and albumin – nephrotic syndrome
  • C3 and C4 – post infectious glomerulonephritis
  • Anti-streptolysin O titre – post-streptococcal glomerulonephritis
  • Rental ultrasound or CT scan – anatomic abnormalities
  • Timed urine testing – hypercalciuria, proteinuria
  • Antinuclear antibody – immunologic diseases
  • Check other family members – familial hematuria

Learning Point
The most common cause of hematuria (gross or microscopic) is idiopathic.
The differential diagnosis of hematuria can be remembered using the pneumonic SHIRT:

  • S – Stones (Urolithiasis)
  • H – Hematologic abnormalities
    • AV malformations
    • Coagulopathy
    • Sickle cell trait or disease
  • I – Infection, Iatrogenic, Idiopathic, Immunologic
    • Benign familial hematuria, idiopathic
    • Hemorrhagic cystitis, often viral
    • Collagen vascular diseases
    • Epididymitis
    • Exercise
    • Medications
    • Menses
    • Urinary tract infection/Pyelonephritis
    • Vasculitis, i.e. Hemolytic uremic syndrome
  • R – Renal abnormalities
    • Anatomic abnormalities, i.e. Ureteropelvic junction obstruction, renal cysts
    • Alport’s syndrome
    • Nephritis, i.e. Post-streptococcal glomerulonephritis
  • T – Tumor, Trauma
    • Hypercalciuria with or without urolithiasis
    • Foreign body
    • Perineal irritation/meatal irritation
    • Trauma
    • Urinary tract tumor

A recent study reported on 228 patients seen for gross hematuria in a referral pediatric nephrology clinic (see Bergstein, et.al. in To Learn More below). Only one case of urinary tract infection and one tumor was reported. The causes of gross hematuria in this series were:

	No diagnosis                            86
	Hypercalcuria without nephrolithiasis   51
	IgA Nephropathy                         34
	Post-streptococcal glomerulonephritis   21
	Exercise                                 8
	13 other causes with < 3 cases          26

Questions for Further Discussion
1. What is the differential diagnosis for microscopic hematuria?
2. What is the follow-up for a patient with hematuria?
3. What are the indications for a renal biopsy?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

To view current news articles on this topic check Google News.

Berkowitz C. Pediatrics A Primary Care Approach. WB Saunders Co. Philadelphia, PA. 1996:265-270.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1663-1665.

Woodhead JC. Pediatric Clerkship Guide. Mosby. St. Louis MO, 2003:262-276, 560-563.

Bergstein J, Leiser J, Andreoli S. The Clinical Significance of Asymptomatic Gross and Microscopic Hematuria in Children. Arch Pediatr Adolesc Med. 2005;159:353-355. Available from the Internet at: http://archpedi.ama-assn.org/cgi/content/full/159/4/353 (cited 06/23/05).

Author
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

Date
August 29, 2005

Published