What is the next step in evaluating a patient with hematuria (blood in urine) without white blood cells (WBC) or nitrates, and a history of possible kidney issues?

Evaluation of Hematuria Without WBC or Nitrites

Confirm true microscopic hematuria with microscopic urinalysis showing ≥3 RBCs per high-power field before initiating any workup, then proceed with risk stratification and complete urologic evaluation including cystoscopy and upper tract imaging for intermediate- to high-risk patients. 1, 2

Initial Confirmation and Exclusion of Benign Causes

• Do not rely on dipstick testing alone—dipstick has only 65-99% specificity and requires microscopic confirmation with ≥3 RBCs/HPF on at least two of three properly collected clean-catch midstream urine specimens 1, 2

• The absence of WBC and nitrites effectively rules out urinary tract infection as the cause, eliminating the need for urine culture or empiric antibiotics 2, 3

• Exclude transient benign causes by repeating urinalysis 48 hours after cessation of potential triggers: menstruation, vigorous exercise, or recent sexual activity 2, 3

• Never attribute hematuria to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves, and evaluation must proceed regardless 1, 2

Risk Stratification for Malignancy

The 2025 AUA/SUFU guidelines stratify patients into three risk categories based on age, smoking history, and degree of hematuria 2, 4:

High-Risk Features (requiring cystoscopy + CT urography):

• Age ≥60 years (either sex) 2, 4
• Smoking history >30 pack-years 2, 4

• 25 RBCs/HPF on urinalysis 2, 4

• Any history of gross hematuria 1, 2
• Occupational exposure to benzenes or aromatic amines 2, 3
• Irritative voiding symptoms (urgency, frequency, nocturia) without infection 2, 4

Intermediate-Risk Features (shared decision-making for cystoscopy + imaging):

• Women age 50-59 years or men age 40-59 years 2
• Smoking history 10-30 pack-years 2
• 11-25 RBCs/HPF 2

Low-Risk Features (may defer imaging, repeat UA in 6 months):

• Women <50 years or men <40 years 2
• Never smoker or <10 pack-years 2
• 3-10 RBCs/HPF 2

Distinguishing Glomerular from Non-Glomerular Sources

Before proceeding with urologic evaluation, assess for glomerular disease indicators 2, 3:

• Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular origin) and red cell casts (pathognomonic for glomerular disease) 2, 3

• Check for proteinuria—significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.5) strongly suggests renal parenchymal disease 2, 3

• Assess renal function with serum creatinine, BUN, and complete metabolic panel 2, 3

• Tea-colored or cola-colored urine suggests glomerular bleeding rather than urologic pathology 2

If glomerular features are present (dysmorphic RBCs >80%, red cell casts, significant proteinuria, or elevated creatinine), refer to nephrology in addition to completing urologic evaluation—malignancy can coexist with medical renal disease 2, 3

Complete Urologic Evaluation for Non-Glomerular Hematuria

For patients with confirmed microscopic hematuria without glomerular features and with intermediate- to high-risk factors 1, 2:

Upper Tract Imaging:

• Multiphasic CT urography is the preferred modality—includes unenhanced, nephrographic, and excretory phases to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 2, 3
• If CT is contraindicated (renal insufficiency, contrast allergy), use MR urography or renal ultrasound with retrograde pyelography 2
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 2

Lower Tract Evaluation:

• Cystoscopy is mandatory for all intermediate- and high-risk patients to visualize bladder mucosa, urethra, and ureteral orifices 1, 2
• Flexible cystoscopy is preferred over rigid cystoscopy—causes less pain with equivalent or superior diagnostic accuracy 2

Additional Testing:

• Do not obtain urine cytology or molecular markers in the initial evaluation—not recommended by current guidelines 1
• Voided urine cytology may be considered in very high-risk patients (age >80 years, heavy smoking history) but is not part of standard initial workup 2

Follow-Up Protocol for Negative Initial Evaluation

If the complete workup is negative but hematuria persists 2, 3:

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 2, 3

• After two consecutive negative annual urinalyses, no further testing for asymptomatic microhematuria is necessary 2

• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 2, 3

Immediate re-evaluation is warranted if 2, 3:

• Gross hematuria develops (30-40% malignancy risk) 1, 2
• Significant increase in degree of microscopic hematuria occurs 2
• New urologic symptoms appear (flank pain, dysuria, irritative voiding) 2
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 2, 3

Critical Pitfalls to Avoid

• Never ignore even self-limited gross hematuria—carries 30-40% malignancy risk and requires urgent urologic referral 1, 2

• Do not defer evaluation due to anticoagulation—malignancy risk is similar regardless of anticoagulation status 2, 3

• Do not screen asymptomatic adults with urinalysis for cancer detection—hematuria found incidentally still requires appropriate evaluation based on risk stratification 1

• Do not attribute persistent hematuria to benign prostatic hyperplasia without proving prostatic origin through appropriate evaluation—concurrent malignancy must be excluded 2

• Given the patient's history of possible kidney issues, nephrology referral is indicated if any glomerular features develop during follow-up (proteinuria, hypertension, declining renal function) 2, 3