What is the appropriate workup for hematuria?

Workup for Hematuria

The appropriate workup for hematuria depends critically on whether the hematuria is gross (visible) or microscopic, the patient's age and risk factors, and whether features suggest a glomerular versus urologic source.

Initial Confirmation and Classification

Confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field (RBC/HPF) on at least two of three properly collected clean-catch midstream urine specimens before initiating any extensive workup. 1, 2 Dipstick testing alone has only 65-99% specificity and produces false positives from myoglobin, hemoglobin, menstrual contamination, or vigorous exercise. 1, 2

Gross (Visible) Hematuria

Any episode of gross hematuria in an adult warrants urgent urologic evaluation with cystoscopy and upper tract imaging, given the 30-40% risk of malignancy, regardless of whether bleeding is self-limited or a benign cause is suspected. 1, 3 This requires same-day or next-day urologic referral. 1

Microscopic Hematuria

For microscopic hematuria, proceed with risk stratification and determine whether features suggest glomerular versus non-glomerular sources. 1, 2

Distinguishing Glomerular from Non-Glomerular Sources

Examine urinary sediment for dysmorphic RBCs (>80% indicates glomerular disease), red cell casts (pathognomonic for glomerular disease), and quantify proteinuria using spot urine protein-to-creatinine ratio. 1, 2, 3

Features Suggesting Glomerular Disease:

• Tea-colored or cola-colored urine 1
• Dysmorphic RBCs >80% on phase-contrast microscopy 1, 3
• Red blood cell casts (pathognomonic) 1, 3
• Significant proteinuria (protein-to-creatinine ratio >0.5 g/g) 1, 3
• Elevated serum creatinine 1, 3
• Hypertension accompanying hematuria 1

If glomerular features are present, refer to nephrology in addition to completing urologic evaluation, as malignancy can coexist with medical renal disease. 1

Features Suggesting Non-Glomerular (Urologic) Source:

• Bright red blood 1
• Normal-shaped (isomorphic) RBCs 3
• Minimal or no proteinuria 3
• Normal serum creatinine 3

Risk Stratification for Urologic Malignancy

For confirmed microscopic hematuria without glomerular features, stratify patients by risk to determine the extent of urologic evaluation needed. 1, 3

High-Risk Features (require full urologic workup: cystoscopy + CT urography):

• Age ≥60 years (both men and women) 1, 3
• Smoking history >30 pack-years 1, 3
• Any history of gross hematuria 1, 3
• Occupational exposure to bladder carcinogens (benzenes, aromatic amines) 1, 3
• Irritative voiding symptoms without documented infection 1, 3
• Degree of hematuria >25 RBC/HPF 1, 3

Intermediate-Risk Features (shared decision-making regarding cystoscopy/imaging):

• Men age 40-59 years 3
• Women age ≥60 years with lower-risk features 3
• Smoking history 10-30 pack-years 3
• Hematuria 11-25 RBC/HPF 3

Low-Risk Features (may defer extensive imaging):

• Men <40 years and women <60 years 3
• Never smoker or <10 pack-years 3
• Hematuria 3-10 RBC/HPF 3

Complete Urologic Evaluation (for High-Risk Patients)

Laboratory Studies:

• Serum creatinine and complete metabolic panel to assess renal function 1, 2
• Complete urinalysis with microscopy 1, 2
• Urine culture if infection suspected (obtain before antibiotics) 1, 2
• Voided urine cytology for high-risk patients (age >60, smoking history, occupational exposure) 1, 2

Upper Tract Imaging:

Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis in intermediate- and high-risk patients. 1, 2 This includes unenhanced, nephrographic, and excretory phases to comprehensively evaluate kidneys, collecting systems, ureters, and bladder. 1

If CT is contraindicated (renal insufficiency or contrast allergy), MR urography or renal ultrasound with retrograde pyelography are alternatives, though less optimal. 1

Lower Tract Evaluation:

Cystoscopy is mandatory for all patients with gross hematuria and for microscopic hematuria patients with intermediate or high-risk features. 1, 2 Flexible cystoscopy is preferred over rigid cystoscopy because it causes less pain while providing equivalent or superior diagnostic accuracy. 1

Special Considerations

Anticoagulation/Antiplatelet Therapy:

Do not attribute hematuria to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves, and evaluation should proceed regardless. 1, 3

Urinary Tract Infection:

If microscopic hematuria resolves within six weeks after completing antibiotics in a low-risk patient, no further urologic workup is required. 1 However, persistent microscopic hematuria after infection treatment requires immediate comprehensive urologic evaluation. 1

Pediatric Patients:

• For isolated microscopic hematuria without proteinuria, imaging is usually not appropriate initially 4, 3
• For gross hematuria, renal and bladder ultrasound is first-line imaging to exclude tumors, stones, and anatomic abnormalities 4, 3
• For traumatic hematuria with concerning mechanism, multiorgan injury, deceleration injury, flank pain/ecchymosis, or congenital renal abnormalities, CT with IV contrast is recommended even with only microscopic hematuria 4, 3

Follow-Up Protocol

If complete workup is negative but hematuria persists, repeat urinalysis, voided urine cytology, and blood pressure measurement at 6,12,24, and 36 months. 1, 2 After two consecutive negative annual urinalyses, no further testing is necessary. 1

Immediate Re-Evaluation Warranted If:

• Gross hematuria develops 1, 2
• Significant increase in degree of microscopic hematuria 1, 2
• New urologic symptoms appear 1, 2
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Critical Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 3
• Do not defer evaluation due to anticoagulation 1, 3
• Do not rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBCs/HPF before initiating workup 1, 2
• Do not delay urologic referral for gross hematuria even if bleeding resolves spontaneously 3
• Recognize that glomerular features do not eliminate the need for urologic evaluation—both evaluations should be completed 1