How to evaluate a patient with hematuria (blood in the urine) and potential underlying kidney disease?

Evaluation of Red Urine

Begin by confirming true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream specimens, as dipstick testing alone has limited specificity (65-99%) and can produce false positives. 1

Initial Confirmation and Exclusion of Pseudohematuria

• Verify microscopic hematuria before initiating any workup, as dipstick positivity from myoglobin, hemoglobin, menstrual contamination, or certain foods/medications does not constitute true hematuria 1, 2
• Collect properly obtained clean-catch midstream specimens, avoiding contamination from menstruation, vigorous exercise within 48 hours, or recent sexual activity 1, 2
• If urinary tract infection is suspected based on symptoms or urinalysis findings, obtain urine culture before antibiotics, treat appropriately, and repeat urinalysis 6 weeks after treatment completion to confirm resolution 2

Distinguish Glomerular from Non-Glomerular Sources

The presence of tea-colored or cola-colored urine, significant proteinuria (>500 mg/24 hours), dysmorphic RBCs (>80%), or red cell casts indicates glomerular disease and requires nephrology referral in addition to completing urologic evaluation. 3, 1

Glomerular indicators:

• Dysmorphic RBCs >80% on phase contrast microscopy (though this requires specialized equipment and expertise not available in most laboratories) 1, 4
• Red cell casts (pathognomonic for glomerular disease) 3, 1
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g or >500 mg/24 hours) 1, 5
• Tea-colored urine appearance 3, 1
• Elevated serum creatinine or declining renal function 1

Non-glomerular indicators:

• Bright red blood or clots suggest lower urinary tract bleeding 1
• Normal-appearing RBCs >80% on microscopy 1
• Absence of proteinuria or only trace amounts 3

Risk Stratification for Urologic Malignancy

All patients with gross hematuria require urgent urologic evaluation with cystoscopy and upper tract imaging regardless of whether bleeding is self-limited, as gross hematuria carries a 30-40% risk of malignancy. 1, 2

High-risk features requiring complete urologic evaluation:

• Age ≥60 years (males) or ≥60 years (females) 1
• Smoking history >30 pack-years 1
• Any history of gross hematuria 1, 2
• >25 RBCs per high-power field on microscopy 1
• Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 1, 2
• Irritative voiding symptoms (urgency, frequency, nocturia) without infection 1

Intermediate-risk features (shared decision-making for cystoscopy/imaging):

• Age 40-59 years (males) or 50-59 years (females) 1
• Smoking history 10-30 pack-years 1
• 11-25 RBCs per high-power field 1

Low-risk features (may defer imaging, repeat UA in 6 months):

• Age <40 years (males) or <50 years (females) 1
• Never smoker or <10 pack-years 1
• 3-10 RBCs per high-power field on single urinalysis 1
• No additional risk factors 1

Complete Urologic Evaluation Protocol

For patients with confirmed non-glomerular hematuria and risk factors, proceed with multiphasic CT urography (preferred) and cystoscopy to exclude malignancy. 1, 2

Upper tract imaging:

• Multiphasic CT urography is the preferred modality, including unenhanced, nephrographic, and excretory phases to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1
• MR urography or renal ultrasound with retrograde pyelography are alternatives if CT is contraindicated (renal insufficiency, contrast allergy) 1
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation in adults 1

Lower tract evaluation:

• Flexible cystoscopy is mandatory for all patients with gross hematuria and microscopic hematuria with risk factors, as it causes less pain and has equivalent or superior diagnostic accuracy compared to rigid cystoscopy 1, 2
• Voided urine cytology should be obtained in high-risk patients to detect high-grade urothelial carcinomas and carcinoma in situ 1

Laboratory evaluation:

• Serum creatinine, BUN, complete metabolic panel to assess renal function 1
• Complete blood count with platelets to evaluate for coagulopathy 1
• Urine culture if infection suspected, preferably before antibiotics 1

Pediatric Considerations (Age-Specific Approach)

Children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs are unlikely to have clinically significant renal disease and do not require imaging. 3

• Renal ultrasound is the preferred modality in children to assess kidney anatomy, size, and position before potential renal biopsy 3
• No imaging indicated for isolated microscopic hematuria without proteinuria in children 3
• CT is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria in children 3
• Gross hematuria in children requires renal and bladder ultrasound to exclude nephrolithiasis, anatomic abnormalities, and rarely renal or bladder tumors 3

Follow-Up Protocol for Negative Initial Evaluation

If the complete workup is negative but hematuria persists, repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 1, 2

• After two consecutive negative annual urinalyses, no further testing for asymptomatic microhematuria is necessary 1
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 1
• Immediate re-evaluation warranted if gross hematuria develops, significant increase in microscopic hematuria occurs, new urologic symptoms appear, or development of hypertension/proteinuria 1, 2

Critical Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 2
• Do not defer evaluation due to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves 1, 2
• Do not rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBCs/HPF before initiating workup 1, 2
• Do not attribute significant proteinuria solely to hematuria—total protein excretion >1,000 mg/24 hours cannot be explained by hematuria alone and requires nephrology evaluation 5
• Do not prescribe additional antibiotics for persistent hematuria after appropriate UTI treatment—this delays cancer diagnosis and provides false reassurance 1