Evaluation and Management of Microscopic Hematuria

Definition and Diagnostic Confirmation

Microscopic hematuria is definitively diagnosed when ≥3 red blood cells per high-power field (RBC/HPF) are present on microscopic examination of a properly collected urine specimen. 1, 2

Dipstick testing alone is insufficient—it has only 65-99% specificity and produces false positives from myoglobin, hemoglobin, menstrual blood, or contaminants 2, 3
Confirm with microscopic urinalysis on at least two of three properly collected clean-catch midstream specimens before initiating any workup 2, 4
In women, specimens with >2 squamous epithelial cells per HPF indicate contamination and should be recollected—ideally by catheterization if repeated voided specimens are inadequate 5
A single positive specimen (≥3 RBC/HPF) is sufficient to proceed with evaluation in patients with high-risk features 2

Risk Stratification (AUA/SUFU 2020 Guidelines)

The 2020 AUA/SUFU guidelines stratify patients into low-risk, intermediate-risk, and high-risk categories based on multiple factors: 1, 2

High-Risk Features (Require Full Urologic Evaluation: Cystoscopy + CT Urography)

Age ≥60 years (both men and women) 1, 2
Smoking history >30 pack-years 1, 2
25 RBC/HPF on urinalysis 1, 2
Any history of gross hematuria (even if self-limited) 1, 2
Occupational exposure to benzenes, aromatic amines, or other bladder carcinogens 2, 3
Irritative voiding symptoms (urgency, frequency, dysuria) without documented infection 2, 3

Intermediate-Risk Features (Shared Decision-Making Regarding Cystoscopy/Imaging)

Men age 40-59 years or women age 50-59 years 2, 3
Smoking history 10-30 pack-years 2, 3
11-25 RBC/HPF on urinalysis 2, 3

Low-Risk Features (May Defer Extensive Imaging)

Men <40 years or women <50 years 2, 3
Never smoker or <10 pack-years 2, 3
3-10 RBC/HPF 2, 3

Initial Laboratory Evaluation

Urinalysis with Microscopy

Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular origin) and red cell casts (pathognomonic for glomerular disease) 2, 4, 6
Assess for proteinuria using spot urine protein-to-creatinine ratio (normal <0.2 g/g; >0.5 g/g suggests renal parenchymal disease) 2, 7

Serum Creatinine and Renal Function

Measure serum creatinine and estimate GFR to identify renal insufficiency 2, 4
Elevated creatinine with hematuria suggests glomerular disease 2, 7

Urine Culture

Obtain urine culture before starting antibiotics if infection is suspected 2, 3
If UTI is confirmed, treat appropriately and repeat urinalysis 6 weeks after treatment completion 2, 3
If hematuria resolves after treating infection in a low-risk patient, no further workup is needed 2, 3
If hematuria persists after infection treatment, proceed with full urologic evaluation 2, 3

Distinguishing Glomerular vs. Urologic Sources

Glomerular Indicators (Warrant Nephrology Referral)

Dysmorphic RBCs >80% of urinary sediment 2, 4, 6
Red cell casts (pathognomonic for glomerular bleeding) 2, 4
Significant proteinuria (protein-to-creatinine ratio >0.5 g/g or >500 mg/24 hours) 2, 7
Elevated serum creatinine or declining renal function 2, 7
Hypertension accompanying hematuria and proteinuria 2, 7
Tea-colored or cola-colored urine 2

Important: 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 2, 6

Urologic Indicators (Require Cystoscopy and Imaging)

Predominantly normal-shaped (isomorphic) RBCs (>80% of sediment) 2, 6
Minimal or no proteinuria 2, 6
Age >35-40 years 2, 4
Smoking history 2, 4
Occupational chemical exposure 2, 3

Complete Urologic Evaluation for Non-Glomerular Hematuria

Upper Tract Imaging: Multiphasic CT Urography

Multiphasic CT urography is the preferred imaging modality for intermediate- and high-risk patients. 1, 2, 4

Includes unenhanced, nephrographic, and excretory phases 2
Detects renal cell carcinoma, transitional cell carcinoma, and urolithiasis with 96% sensitivity and 99% specificity for urothelial malignancy 2
Alternative imaging (MR urography or renal ultrasound with retrograde pyelography) may be used if CT is contraindicated due to renal insufficiency or contrast allergy 2, 4

Renal ultrasound alone is insufficient for comprehensive upper tract evaluation. 2, 4

Lower Tract Evaluation: Flexible Cystoscopy

Cystoscopy is mandatory for all patients ≥40 years with microscopic hematuria and for all patients with gross hematuria. 1, 2, 4

Flexible cystoscopy is preferred over rigid cystoscopy—it causes less pain with equivalent or superior diagnostic accuracy 2, 7, 4
Directly visualizes bladder mucosa, urethra, and ureteral orifices to detect transitional cell carcinoma (the most common malignancy in hematuria patients) 2, 4
Bladder cancer accounts for 30-40% of gross hematuria cases and 2.6-4% of microscopic hematuria cases 2

Voided Urine Cytology

Consider in high-risk patients (age >60 years, smoking >30 pack-years, occupational exposures) to detect high-grade urothelial carcinomas and carcinoma in situ 2, 4
Not recommended as part of routine initial evaluation in low-risk patients 2, 4

Follow-Up Protocol After Negative Initial Evaluation

If the complete urologic workup is negative but hematuria persists: 1, 2, 3

Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1, 2, 3
After two consecutive negative annual urinalyses, no further testing is necessary 1, 2
Consider repeat complete evaluation (cystoscopy and imaging) within 3-5 years for persistent hematuria in high-risk patients 2, 3

Immediate Re-Evaluation Is Warranted If:

Gross hematuria develops 1, 2, 3
Significant increase in degree of microscopic hematuria 1, 2, 3
New urologic symptoms appear (flank pain, irritative voiding) 1, 2, 3
Development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2, 3

Critical Pitfalls to Avoid

Never ignore gross hematuria—even if self-limited, it carries a 30-40% malignancy risk and mandates urgent urologic referral 2
Do not attribute hematuria to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria; evaluation must proceed regardless 2, 3, 4
Do not rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBC/HPF before initiating workup 2, 3
Do not defer evaluation in patients >35-40 years—age alone is a sufficient risk factor for full urologic workup 2, 4
Do not omit cystoscopy based on imaging alone—bladder cancer requires direct visualization and cannot be excluded by CT 2
Do not assume infection explains persistent hematuria—if hematuria persists 6 weeks after treating UTI, proceed with full urologic evaluation 2, 3

Special Populations

Pediatric Considerations

Children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs do not require imaging—clinical follow-up is appropriate 2
Renal ultrasound is the preferred first-line imaging for children with gross hematuria to exclude nephrolithiasis and anatomic abnormalities 2
CT is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria in children 2

Elderly Patients

Males ≥60 years are automatically classified as high-risk and require cystoscopy and CT urography regardless of other factors 1, 2
Women ≥60 years with any additional risk factor (smoking, gross hematuria, >25 RBC/HPF) also require full evaluation 1, 2

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