What is the appropriate work‑up for a patient with moderate hematuria on urinalysis?

Evaluation of Moderate Hematuria on Urinalysis

Moderate hematuria on urinalysis requires immediate microscopic confirmation showing ≥3 RBCs per high-power field before initiating any workup, followed by risk-stratified urologic evaluation that includes cystoscopy and upper tract imaging for most adults over 35-40 years. 1

Step 1: Confirm True Hematuria

• Obtain microscopic urinalysis on a properly collected clean-catch midstream specimen to verify ≥3 RBCs/HPF, as dipstick testing has only 65-99% specificity and produces false positives from myoglobin, hemoglobin, menstrual contamination, or other substances 1, 2
• Require confirmation on at least 2 of 3 specimens in low-risk patients before proceeding with extensive imaging, though a single positive specimen may justify full evaluation in high-risk individuals 1, 3
• Document the exact RBC count (e.g., 0-3,4-10,11-25,26-50, >50 RBCs/HPF) as higher degrees carry greater malignancy risk 3, 4

Step 2: Distinguish Glomerular from Urologic Sources

Glomerular Indicators (Nephrology Referral)

• Tea-colored or cola-colored urine suggests glomerular bleeding 1, 4
• >80% dysmorphic RBCs on urinary sediment examination with phase-contrast microscopy 1, 4
• Red blood cell casts are pathognomonic for glomerular disease 1, 4
• Significant proteinuria with protein-to-creatinine ratio >0.5 g/g (or >500 mg/24h) 1
• Elevated serum creatinine or declining renal function 1

Urologic Indicators (Proceed with Full Urologic Workup)

• Normal-shaped RBCs (>80%) with minimal or no proteinuria 1, 4
• Bright red or pink urine suggests lower urinary tract source 1
• Age >35-40 years automatically increases urologic malignancy risk 1, 2

Critical Pearl: The presence of glomerular features does not eliminate the need for urologic evaluation—both evaluations should be completed, as malignancy can coexist with medical renal disease 1

Step 3: Risk Stratification for Urologic Malignancy

High-Risk Features (Mandatory Full Workup: CT Urography + Cystoscopy)

• Age ≥60 years (men or women) 1
• Smoking history >30 pack-years 1, 4
• Any history of gross hematuria (even if currently microscopic) 1
• Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 1, 4
• Irritative voiding symptoms (urgency, frequency, nocturia) without documented infection 1
• >25 RBCs/HPF on microscopy 1, 5

Intermediate-Risk Features (Shared Decision-Making)

• Age 40-59 years (men) 1
• Smoking history 10-30 pack-years 1

Low-Risk Features (May Defer Extensive Imaging)

• Age <40 years with no other risk factors 1
• Never smoker or <10 pack-years 1
• 3-10 RBCs/HPF 1

Step 4: Complete Urologic Evaluation (for High/Intermediate Risk)

Upper Tract Imaging

• Multiphasic CT urography is the gold standard with 96% sensitivity and 99% specificity for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 5, 6
• Must include three phases: unenhanced (detects stones), nephrographic (evaluates renal parenchyma), and excretory (assesses urothelium) 1, 5
• Alternative imaging if CT contraindicated: MR urography or renal ultrasound with retrograde pyelography 1
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 1

Lower Tract Evaluation

• Flexible cystoscopy is mandatory for all patients with gross hematuria and for microscopic hematuria patients ≥40 years or with high-risk features 1, 2
• Flexible cystoscopy is preferred over rigid cystoscopy due to less pain with equivalent or superior diagnostic accuracy 1
• Cystoscopy provides direct visualization of bladder mucosa, urethra, and ureteral orifices to exclude bladder cancer (the most common malignancy in hematuria cases) 1, 4

Laboratory Testing

• Serum creatinine and BUN to assess renal function 1, 5
• Complete urinalysis with microscopy including examination for dysmorphic RBCs, casts, proteinuria, WBCs, and bacteria 1
• Urine culture if infection suspected, preferably before antibiotics 1, 5
• Voided urine cytology may be considered as adjunct in high-risk patients (age >60, smoking >30 pack-years, occupational exposures) but should not be used as initial screening tool 1

Step 5: Address Common Clinical Scenarios

If Urinary Tract Infection Suspected

• Obtain urine culture before antibiotics 1, 5
• Treat infection appropriately and repeat urinalysis 6 weeks after treatment 1
• If hematuria resolves after infection treatment in a low-risk patient, no further workup needed 1
• If hematuria persists after infection treatment, proceed with full urologic evaluation—infection does not exclude concurrent malignancy 1, 5

If Patient on Anticoagulation/Antiplatelet Therapy

• Do not attribute hematuria to anticoagulation—these medications may unmask underlying pathology but do not cause hematuria 1, 4, 2
• Proceed with full evaluation regardless of medication regimen 1

If Gross (Visible) Hematuria

• Urgent urologic referral (within 24-48 hours) is mandatory even if bleeding is self-limited, as gross hematuria carries a 30-40% risk of malignancy 1, 2, 7
• All patients with gross hematuria require cystoscopy and upper tract imaging regardless of age or other factors 1

Step 6: Follow-Up Protocol for Negative Initial Evaluation

• If initial workup is negative but hematuria persists, perform repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 8, 1
• After two consecutive negative annual urinalyses, no further testing is necessary 1
• Immediate re-evaluation is warranted if: gross hematuria develops, significant increase in microscopic hematuria, new urologic symptoms appear, or development of hypertension/proteinuria/glomerular bleeding 8, 1
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 8

Critical Pitfalls to Avoid

• Never ignore gross hematuria even if self-limited—30-40% malignancy risk mandates urgent evaluation 1, 4
• Never rely solely on dipstick without microscopic confirmation of ≥3 RBCs/HPF 1, 2
• Never defer evaluation due to anticoagulation—these medications unmask rather than cause hematuria 1, 4
• Never assume benign cause in patients >35-40 years without completing full urologic workup 1, 6
• Never use ultrasound alone for upper tract evaluation—it misses 62% of ureteral stones and has poor sensitivity for small renal masses 1

Special Populations

Pediatric Patients

• Children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs do not require imaging 1, 5
• Renal ultrasound is appropriate first-line imaging for children with gross hematuria to exclude nephrolithiasis and anatomic abnormalities 1, 5
• CT is not appropriate in initial evaluation of isolated nonpainful, nontraumatic hematuria in children 1, 5

Elderly Males (>60 years)

• Automatically classified as high-risk requiring full urologic evaluation with cystoscopy and CT urography regardless of other factors 1
• Benign prostatic hyperplasia may cause hematuria but does not exclude concurrent malignancy 1

The overwhelming majority of patients who undergo thorough initial workup without positive findings will remain cancer-free, but persistent hematuria in high-risk populations requires vigilant surveillance as hematuria may precede bladder cancer diagnosis by many years. 8