What are the guidelines for evaluating and managing a patient with hematuria, considering factors such as age, sex, and medical history, including conditions like urinary tract infection, bladder cancer, and impaired renal function?

Guidelines for Hematuria Evaluation and Management

Define and Confirm True Hematuria

Microscopic hematuria must be confirmed as ≥3 red blood cells per high-power field (RBC/HPF) on microscopic urinalysis—dipstick positivity alone is insufficient and should never trigger a full workup. 1

• Dipstick testing has limited specificity (65-99%) and can produce false positives from myoglobinuria, povidone iodine, or dehydration 1, 2
• For asymptomatic microscopic hematuria, confirm with microscopic examination on at least 2 of 3 properly collected clean-catch midstream specimens before proceeding 1
• High-risk patients (discussed below) may warrant full evaluation after a single positive specimen showing ≥3 RBC/HPF 3

Immediate Urologic Referral: Gross Hematuria

All adults with gross hematuria require urgent urologic evaluation with cystoscopy and upper tract imaging, even if self-limited, because the malignancy risk is 30-40%. 1, 4

• This recommendation applies regardless of whether the patient is on anticoagulation or antiplatelet therapy 1, 4
• Painless gross hematuria has particularly strong association with malignancy 1

Initial Clinical Assessment for Microscopic Hematuria

Obtain a focused history targeting specific high-risk features 5, 4:

• Smoking history: Quantify as pack-years (>30 pack-years = high risk; 10-30 = intermediate risk; <10 = low risk) 5, 4
• Age and sex: Men ≥60 years and women ≥60 years have elevated malignancy risk 5, 4
• History of gross hematuria: Even remote episodes significantly increase cancer risk 1, 4
• Occupational exposures: Benzenes, aromatic amines, or other chemical carcinogens 5, 4
• Irritative voiding symptoms: Urgency, frequency, nocturia may indicate bladder cancer or interstitial cystitis 5, 4

Physical examination should include 1, 5:

• Blood pressure measurement (hypertension suggests renal parenchymal disease) 1, 5
• Pelvic examination in women to exclude gynecologic or urethral pathology 1
• Digital rectal examination in men to assess prostate 1

Exclude Benign Transient Causes

Before proceeding with extensive workup, exclude and treat reversible causes 1, 5, 4:

• Urinary tract infection: Obtain urine culture before starting antibiotics, then repeat urinalysis 6 weeks post-treatment 5, 4
• Menstruation: Repeat urinalysis at appropriate time in cycle 4
• Vigorous exercise or sexual activity: Repeat urinalysis 48 hours after cessation 5, 4
• Recent urologic procedures: Repeat urinalysis after appropriate interval 5

If a benign cause is identified and treated, repeat urinalysis to confirm resolution 1, 5

Risk Stratification Using 2025 AUA/SUFU Criteria

Categorize patients into risk groups based on the following factors 5, 4:

High Risk (malignancy risk 1.3-6.3%):

• Men ≥60 years 5, 4
• Smoking history >30 pack-years 5, 4
• History of gross hematuria 5, 4
• Occupational chemical exposure 5, 4

Intermediate Risk (malignancy risk 0.2-3.1%):

• Women ≥60 years 5
• Men 40-59 years 5
• Smoking history 10-30 pack-years 5

Low/Negligible Risk (malignancy risk 0-0.4%):

• Women <60 years 5
• Men <40 years 5
• Never smoker or <10 pack-years 5

Distinguish Glomerular from Non-Glomerular Sources

Before urologic referral, assess for signs of primary renal disease 1, 4, 2:

Features suggesting glomerular disease:

• Dysmorphic RBCs (>80% on phase contrast microscopy) or red cell casts 1, 4
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g or >500-1000 mg/24h) 5, 4
• Elevated serum creatinine or declining renal function 5, 4
• Tea-colored or cola-colored urine 4
• Hypertension with hematuria 5, 4

If glomerular features present: Refer to nephrology rather than urology 1, 4

Complete Urologic Evaluation for Intermediate and High-Risk Patients

For patients with non-glomerular microscopic hematuria and intermediate or high-risk features, perform both cystoscopy and upper tract imaging. 1, 5

Upper Tract Imaging

• Multiphasic CT urography is the preferred modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 5, 4, 3
• CT urography should include unenhanced, nephrographic, and excretory phases 4
• If CT contraindicated (renal insufficiency, contrast allergy): Consider MR urography or renal ultrasound with retrograde pyelography 4
• Traditional intravenous urography (IVU) is acceptable but has limited sensitivity for small renal masses 4

Cystoscopy

• Flexible cystoscopy is preferred over rigid cystoscopy (less pain, fewer post-procedure symptoms, equivalent or superior diagnostic accuracy) 4, 3
• Mandatory for all intermediate and high-risk patients to visualize bladder mucosa, urethra, and ureteral orifices 5, 4, 3

Additional Testing

• Do NOT obtain urinary cytology or urine-based molecular markers in the initial evaluation 1
• Urine cytology may be considered only in highly selected cases with risk factors for carcinoma in situ or persistent irritative symptoms 3
• Serum creatinine to assess renal function 5, 4

Management of Low-Risk Patients

For low-risk patients with confirmed microscopic hematuria and no benign cause identified 5, 4:

• Shared decision-making regarding whether to pursue cystoscopy and imaging 1, 5
• Consider observation with serial urinalysis 5
• Lower threshold for complete evaluation if any concerning features develop 5

Critical Caveats

Anticoagulation/antiplatelet therapy does NOT explain hematuria and should never defer evaluation. 1, 4

• These medications may unmask underlying pathology but do not cause hematuria themselves 1, 4
• Pursue the same evaluation as in patients not on these agents 1

Do not screen asymptomatic adults with urinalysis for cancer detection. 1

Always ask patients with microscopic hematuria about any history of gross hematuria. 1

• Even remote episodes significantly elevate cancer risk 1, 4

Follow-Up for Negative Initial Evaluation

If complete urologic evaluation is negative but hematuria persists 5, 4:

• Repeat urinalysis at 6,12,24, and 36 months 5, 4
• Monitor blood pressure at each visit 5, 4
• Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 5, 4

Immediate re-evaluation is warranted if: 4

• Gross hematuria develops 4
• Significant increase in degree of microscopic hematuria 4
• New urologic symptoms appear 4
• Development of hypertension, proteinuria, or declining renal function 4