> Table of Contents > Hematuria
Hematuria
Tracy O. Middleton, DO
image BASICS
DESCRIPTION
  • Gross (visible) or microscopic (nonvisible) blood in the urine
  • Symptomatic or asymptomatic
EPIDEMIOLOGY
Prevalence
  • Microscopic hematuria in school-aged children: 0.4-4%
  • Microscopic hematuria in asymptomatic adults varies from 0.19% to 31%, depending on population (1).
ETIOLOGY AND PATHOPHYSIOLOGY
  • Trauma
    • Exercise-induced (resolves with rest)
    • Abdominal trauma or pelvic fracture with renal, bladder, or ureteral injury
    • Iatrogenic from abdominal or pelvic surgery; chronic indwelling catheters
    • Foreign body, physical/sexual abuse
  • Neoplasms
    • Urologic malignancies
    • Benign tumors
    • Endometriosis of the urinary tract (suspect in females with cyclic hematuria)
  • Inflammatory causes
    • UTI: most common cause of hematuria in adults
    • Renal diseases: radiation nephritis and cystitis, acute/chronic tubulointerstitial nephritis (due to drugs, infections, systemic disease)
    • Glomerular disease
      • Goodpasture syndrome (antiglomerular basement membrane disease; autoimmune; associated pulmonary hemorrhage)
      • IgA nephropathy
      • Lupus nephritis
      • Henoch-Schönlein purpura
      • Membranoproliferative, poststreptococcal, or rapidly progressive glomerulonephritis (GN)
      • Wegener granulomatosis
    • Endocarditis/visceral abscesses
    • Other infections: schistosomiasis, TB, syphilis
  • Metabolic causes
    • Stones (85% have hematuria)
      • Hypercalciuria: a common cause of both gross and microscopic hematuria in children
      • Hyperuricosuria
  • Congenital/familial causes
    • Cystic disease: polycystic, solitary renal cyst
    • Benign familial hematuria or thin basement membrane nephropathy (autosomal dominant)
    • Alport syndrome (X-linked in 85%; hematuria, proteinuria, hearing loss, corneal abnormalities)
    • Fabry disease (X-linked recessive inborn error of metabolism; vascular kidney disease)
    • Nail-patella syndrome (autosomal dominant; nail and patella hypoplasia; hematuria in 33%)
    • Renal tubular acidosis type 1 (autosomal dominant or autoimmune)
  • Hematologic causes
    • Bleeding dyscrasias (e.g., hemophilia)
    • Sickle cell anemia/trait (renal papillary necrosis)
  • Vascular causes
    • Hemangioma
    • Arteriovenous malformations (rare)
    • Nutcracker syndrome: compression of left renal vein and subsequent renal parenchymal congestion
    • Renal artery/vein thrombosis
    • Arterial emboli to kidney
  • Chemical causes
    • Aminoglycosides, cyclosporine, analgesics, oral contraceptives, Chinese herbs
  • Obstruction
    • Strictures or posterior urethral valves
    • Hydronephrosis from any cause
    • Benign prostatic hyperplasia: Rule out other causes of hematuria.
  • Other causes: loin pain hematuria (most often in young women on oral contraceptives)
RISK FACTORS
  • Smoking
  • Occupational exposures (dyes, rubber, or tire manufacturing)
  • Analgesic abuse (e.g., phenacetin)
  • Medications (e.g., cyclophosphamide)
  • Pelvic irradiation
  • Chronic infection, especially with calculi
  • Recent upper respiratory tract infection
  • Positive family history of renal diseases (stones, GN)
  • Underlying primary renal disorder
  • Chronic indwelling foreign body
image DIAGNOSIS
PHYSICAL EXAM
Considerations
  • Elevated BP, edema, and weight gain: glomerular disease
  • Fever: infection
  • Palpable kidney: neoplasm, polycystic
  • Genitalia: Look for meatal erosion, lesions
DIAGNOSTIC TESTS & INTERPRETATION
  • A hematuria risk index may assist in stratifying patients at risk for urothelial malignancies who require more intensive testing. High-risk indicators are gross hematuria, age >50 years, male gender, and smoking (2)[B].
  • Studies are ongoing using urinary biomarkers + clinical factors to predict the likelihood of bladder cancer (3)[B].
  • American Urological Association (AUA) suggests upper urinary tract imaging in all adults with unexplained hematuria (4)[C].
Initial Tests (lab, imaging)
  • Urine dipstick (sensitivity 91-100%; specificity 65-99%)
    • False negatives are rare but can be caused by high-dose vitamin C.
    • False positives: oxidizers (povidone, bacterial peroxidases, bleach), myoglobin, alkaline urine (>9), semen, food coloring, food (beets, blackberries) (1)
    • Phenazopyridine may discolor the dipstick, making interpretation difficult.
  • Microscopic urinalysis should always be done to confirm dipstick findings and quantify RBCs.
    • AUA defines clinically significant microscopic hematuria as ≥3 RBCs/HPF on a properly collected urinary specimen when there is not an obvious benign cause (4)[C].
    • Positive dipstick but a negative microscopic exam should be followed by 3 repeat tests. If any 1 is positive, proceed with a workup (4)[C].
    • Exclude factitious or nonurinary causes, such as menstruation, mild trauma, exercise, poor collection technique, or chemical/drug causes, through cessation of activity/cause and a repeat urinalysis in 48 hours (1)[C].
    • RBC casts are pathognomonic for glomerular origin; dysmorphic cells are also suggestive.
  • Voided urine cytology
    • No longer recommended by AUA for routine evaluation of hematuria (4)[C]
    • Some still consider cytology in those with risk factors for urinary malignancy (1)[C].
  • Renal function tests (eGFR, BUN, creatinine) to differentiate intrinsic renal disease and to evaluate for risks for imaging contrast dye or certain medications
    • Indicators of renal disease are: significant (>500 mg/day) proteinuria, red cell casts, dysmorphic RBCs, increased creatinine, and albumin:creatinine ratio ≥30 mg/mmol (4)[C],(5)[A].
  • Urine culture if suspected infection/pyuria (1)[C]
  • PT/INR for patients on warfarin or suspected of abusing warfarin
  • Multidetector CT urography (MDCTU); sensitivity 91-100%, specificity 94-97% (1)[C]
    • The initial imaging of choice in nonpregnant adults with unexplained hematuria (1,6)[C]
    • Highly specific and relatively sensitive for the diagnosis of upper urinary tract neoplasms, especially when >1 cm (6)[C]
    • Higher radiation dose; weigh risk of disease versus risk of radiation exposure.
    • Does not obviate the need for cystoscopy, particularly in high-risk patients (6)[C]
    • Presence of calculi on noncontrast does not exclude another diagnosis or need for contrast phase.
    • Visualization of ureters is discontinuous.
    • Less cost-efficient
  • CT
    • Perform unenhanced helical CT for suspected stone disease in children if US is negative (7)[C].
    • Perform CT abdomen and pelvis with contrast in children with traumatic hematuria (7)[C].
  • Renal ultrasound
    • Best for differentiating cystic from solid masses
    • Sensitive for hydronephrosis
    • No radiation or iodinated contrast exposure
    • Cost-efficient
    • Poor sensitivity for renal masses <3 cm
    • P.453

    • Point of care US in the emergency room may help patients with suspected stones avoid CT (8)[B].
    • US can be used first line in patients with contraindications to CTU or at low risk of malignancy (6)[C].
    • Main disadvantage is inability to thoroughly evaluate the urothelium for transitional cell cancer.
  • Magnetic resonance urography (MRU)
    • High sensitivity/specificity for renal parenchyma; less useful for collecting system or stones
    • Can be used in patients with contraindications to MDCTU (4,6)[C]
  • IV urography (IVU)
    • Limited sensitivity for small renal masses and for differentiating cystic from solid masses
    • Addition of US or CT often necessary to evaluate renal parenchyma, so IVU is rarely used.
    • Potential reactions to IV iodine contrast media
  • MRI
    • Similar to CT in sensitivity for renal masses
    • No radiation exposure
    • Least cost-efficient
    • Limited ability to reliably detect urinary tract calcifications (6)[C]
    • Can be combined with retrograde pyelogram (RPG) for patients who cannot tolerate MDCTU or MRU (4)[C]
Diagnostic Procedures/Other
  • Flexible cystoscopy
    • Best for evaluation of bladder pathology, especially small urothelial lesions; negative predictive value for bladder tumors is 99% (1)[C].
    • AUA recommends all patients with hematuria who are ≥35 years of age and all patients with risk factors for bladder cancer regardless of age to receive cystoscopy in addition to imaging (4)[C].
  • Renal biopsy
    • Not routine but may be necessary to diagnose GN or in the face of increasing renal insufficiency
  • RPG
    • Reserved for patients in which findings on MDCTU are equivocal or in addition to US or noncontrast studies in patients who are contraindicated for contrast or MRI (4,6)[C]
    • Sensitive for small lesions of supravesicular collecting system
    • Requires cystoscopy
  • Ureteroscopy/pyeloscopy
    • For visualization of suspected supravesical collecting system lesions
    • Biopsy, excision, fulguration, or extraction of lesions/stones possible
    • Requires anesthesia
    • Requires cystoscopy
    • Risk of injury to collecting system
Follow-Up Tests & Special Considerations
  • Other tests depend on suspected etiology: STD testing, antineutrophil cytoplasmic antibody (ANCA), C3, C4, antistreptolysin O (ASO) titer, hemoglobin electrophoresis (9)[C].
  • Consider genetic testing in patients suspected of having familial hematuria (10)[C].
  • Insufficient evidence to recommend routine use of urinary tumor markers
  • Malignancies are detected in up to 5% of patients with microscopic hematuria and up to 40% of patients with gross hematuria (1)[C].
Pregnancy Considerations
Renal US is initial imaging choice for pregnant patients (6)[C]. MRU or RPG combined with either MRI or US are alternatives (4)[C].
Pediatric Considerations
  • Consider GN, Wilms tumor, child abuse, and hypercalciuria.
  • Isolated asymptomatic microscopic hematuria may not need full workup; these patients rarely need cystoscopy; observe for development of hypertension, gross hematuria, or proteinuria (9)[C].
  • Gross or symptomatic hematuria needs a full workup.
    • If eumorphic RBCs, consider US (rule out stones, congenital abnormalities) and urinary Ca:Cr ratio. Urine Ca:Cr ratio >0.2 is suggestive of hypercalciuria in children >6 years of age (9)[C].
  • If dysmorphic RBCs, consider renal consult.
  • Renal US identifies most congenital and malignant conditions; CT is reserved for cases of suspected trauma (with contrast) or stones (without contrast) (7,9)[C].
image TREATMENT
MEDICATION
None indicated for undiagnosed hematuria
ISSUES FOR REFERRAL
Prompt nephrology referral for proteinuria, red cell casts, elevated serum creatinine, and albumin: creatinine ratio ≥30 mg/mmol (4,5)[A].
SURGERY/OTHER PROCEDURES
Gross hematuria: Clots may require continuous bladder irrigation with a large-bore Foley catheter (2- or 3-way catheter may be helpful) to prevent clot retention.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Some experts still recommend periodic urinalysis; recent literature suggests that, after thorough initial negative investigations (imaging, cystoscopy), no follow-up is indicated for the asymptomatic patient with microscopic hematuria unless symptoms or frank hematuria develop. AUA recommends annual urinalyses in these patients, until two consecutive are negative and the consideration for a repeat workup at 3 to 5 years if hematuria is persistent (1,4)[C].
DIET
Increased fluids for stones or clots
PROGNOSIS
  • Generally excellent for common causes of hematuria
  • Poorer for malignant tumors and certain types of nephritis
  • Persistent asymptomatic microscopic hematuria is associated with an increased risk of end-stage renal disease in patients aged 16 to 25 years.
REFERENCES
1. Sharp VJ, Barnes KT, Erickson BA. Assessment of asymptomatic microscopic hematuria in adults. Am Fam Physician. 2013;88(11):747-754.
2. Loo RK, Lieberman SF, Slezak JM, et al. Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria. Mayo Clin Proc. 2013;88(2):129-138.
3. Lotan Y, Svatek RS, Krabbe LM, et al. Prospective external validation of a bladder cancer detection model. J Urol. 2014;192(5):1343-1348.
4. Davis R, Jones JS, Barocas DA, et al. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol. 2012;188(6 Suppl):2473-2481.
5. Carville S, Wonderling D, Stevens P. Early identification and management of chronic kidney disease in adults: summary of updated NICE guidance. BMJ. 2014;349:g4507.
6. Shen L, Raman SS, Beland MD, et al. Expert Panel on Urologic Imaging. ACR Appropriateness Criteria® Hematuria. Reston, VA: American College of Radiology; 2014.
7. Dillman JR, Coley BD, Karmazyn B, et al. Expert Panel on Pediatric Imaging. ACR Appropriateness Criteria® Hematuria—Child. Reston, VA: American College of Radiology; 2012. http://www.guideline.gov/content.aspx?id=43874. Accessed 2015.
8. Smith-Bindman R, Aubin C, Bailitz J, et al. Ultrasonography versus computed tomography for suspected nephrolithiasis. N Engl J Med 2014;371(12):1100-1110.
9. Massengill SF. Hematuria. Pediatr Rev. 2008;29(10):342-348.
10. Taylor J, Flinter F. Familial haematuria: when to consider genetic testing. Arch Dis Child. 2014;99:857-861.
See Also
&NA;
Algorithm: Hematuria
Codes
&NA;
ICD10
  • R31.9 Hematuria, unspecified
  • R31.1 Benign essential microscopic hematuria
  • R31.0 Gross hematuria
Clinical Pearls
&NA;
  • Screening asymptomatic patients for microscopic hematuria is an “I” recommendation from the USPSTF (1)[B].
  • Asymptomatic hematuria and hematuria persisting after treatment of UTIs must be evaluated.
  • Patients with bladder cancer can have intermittent microscopic hematuria; a thorough evaluation in high-risk patients is needed after just one episode.
  • Routine use of anticoagulants should not cause hematuria unless there is an underlying urologic abnormality (1)[C].
  • Signs of underlying renal disease indicate the need for a nephrologic workup, but a urologic evaluation is still needed in the presence of persistent hematuria (4)[C].