What is the treatment for hematuria (blood in urine) with a negative Urinary Tract Infection (UTI) diagnosis?

Treatment for Hematuria with Negative UTI

The primary treatment for hematuria with a negative UTI diagnosis should focus on identifying and addressing the underlying cause through appropriate diagnostic evaluation, as there is no universal treatment for hematuria itself.

Diagnostic Approach

Initial Assessment

• Rule out benign causes of hematuria:
  • Recent vigorous exercise
  • Menstruation
  • Trauma
  • Recent urological procedures
  • Viral illness 1

Laboratory Evaluation

• Complete urinalysis with microscopic examination (not just dipstick)
• Urine culture to confirm absence of infection
• Renal function tests (eGFR, creatinine, BUN)
• Complete blood count 2

Risk Stratification

Categorize patients into risk groups based on:

• Age (women ≥50 years, men ≥40 years are higher risk)
• Smoking history (>30 pack-years increases risk)
• Intensity of hematuria (gross vs. microscopic)
• Presence of proteinuria
• Family history of renal cell carcinoma
• Occupational exposures 2

Imaging Recommendations

For Microscopic Hematuria without Proteinuria

• Initial imaging is usually not necessary 1, 2
• If persistent, consider ultrasound of kidneys and bladder 1

For Macroscopic (Gross) Hematuria or Hematuria with Proteinuria

• Ultrasound of kidneys and bladder as initial imaging test 2
• For high-risk patients, consider CT urography 1, 2
• For patients with renal insufficiency or contrast allergy, consider MR urography 2

Treatment Based on Underlying Cause

When No Specific Cause Is Found

• If initial evaluation is negative, repeat urinalysis in 3 months
• If hematuria persists after negative urologic workup, conduct yearly urinalyses
• After two consecutive negative annual urinalyses, no further evaluation is necessary 2

For Glomerular Causes

• If glomerulonephritis is suspected (based on dysmorphic RBCs, proteinuria):
  • Refer to nephrology for evaluation
  • Consider blood urea nitrogen test, serum creatinine test, and complete blood count 1
  • For significant proteinuria (>1g/day), strict blood pressure control and monitoring of renal function 2

For Structural Abnormalities

• Treatment depends on the specific finding:
  • Renal stones: appropriate stone management
  • Bladder tumors: referral to urology for further management
  • Benign prostatic hyperplasia: medical or surgical management as appropriate 2

For Interstitial Cystitis

• Consider this diagnosis in patients with persistent hematuria, negative evaluation, and irritative voiding symptoms
• Treatment may include dietary modifications, pelvic floor physical therapy, and medications such as pentosan polysulfate sodium 3

Special Considerations

Patients on Anticoagulants

• Do not assume anticoagulation is the sole cause of hematuria
• Up to 17% of patients on anticoagulants with hematuria have significant underlying pathology 4
• Full evaluation is warranted even with excessive anticoagulation 5

Elderly Patients

• Higher risk of significant pathology
• More likely to have asymptomatic bacteriuria without true infection
• Pyuria is common in absence of infection, particularly in those with lower urinary tract symptoms 6

Follow-up Recommendations

• For persistent or recurrent hematuria after initial negative workup, consider repeat evaluation within 3-5 years 2
• Timely referral to urology or nephrology is crucial, as delays in evaluation can be associated with decreased survival 2

Common Pitfalls

• Assuming a benign cause without complete evaluation in high-risk patients
• Inadequate imaging in high-risk patients
• Treating asymptomatic bacteriuria with antibiotics
• Failing to consider non-infectious causes when UTI has been ruled out 2