What are the recommended diagnostic tests and treatments for hematuria (blood in urine)?

Diagnostic Testing for Hematuria

For blood detected in urine, confirm with microscopic urinalysis showing ≥3 red blood cells per high-power field (RBC/HPF) on two of three properly collected clean-catch midstream specimens before initiating any workup, as dipstick testing alone has limited specificity (65-99%) and should never trigger imaging or further investigation without microscopic confirmation. 1, 2

Initial Confirmation and Collection Technique

• Dipstick positivity must be verified by microscopic examination showing ≥3 RBCs/HPF before proceeding with any evaluation, as false positives are common 1, 2
• Collect clean-catch midstream urine specimens, with proper technique including retraction of foreskin in uncircumcised men; if phimosis prevents adequate collection, obtain a catheterized specimen 3
• Examine the specimen within two hours of collection to ensure accuracy 4
• The recommended definition requires ≥3 RBCs/HPF on two of three properly collected specimens to account for intermittent hematuria in patients with urologic malignancies 1

Risk Stratification for Determining Evaluation Intensity

High-risk patients require full urologic evaluation after even one positive specimen showing ≥3 RBCs/HPF 1, 2:

• Age ≥60 years (men) or ≥60 years (women) 2
• Smoking history >30 pack-years 2

• 25 RBCs/HPF on single urinalysis 2

• History of gross hematuria 2
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1, 5
• History of urologic disorders or pelvic irradiation 5

Complete Urologic Evaluation for Confirmed Hematuria

Laboratory Testing

• Microscopic examination of urinary sediment to assess for dysmorphic RBCs (>80% suggests glomerular origin) and red cell casts (pathognomonic for glomerular disease) 1, 2
• Serum creatinine to evaluate renal function 1, 3
• Urine culture if urinary tract infection suspected; if positive, treat appropriately and repeat urinalysis 6 weeks after treatment completion to confirm hematuria resolution 1, 5
• Voided urine cytology for all patients with risk factors for transitional cell carcinoma, as urothelial cancers are the most commonly detected malignancies in patients with microscopic hematuria 1, 3
• Quantify proteinuria using spot urine protein-to-creatinine ratio (normal <0.2 g/g); significant proteinuria (>500 mg/24 hours) strongly suggests glomerular disease 2

Upper Tract Imaging

• Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma in the pelvicaliceal system or ureter, and urolithiasis 1, 2
• Intravenous urography (IVU) remains an acceptable alternative for upper tract imaging, though it has limited sensitivity for small renal masses 1
• Renal ultrasound with Doppler can evaluate for structural abnormalities and conditions like Nutcracker syndrome (left renal vein compression) 2

Lower Tract Evaluation

• Cystoscopy is mandatory for all patients ≥40 years old with confirmed microscopic hematuria to detect bladder tumors and carcinoma in situ 2, 5
• For patients with risk factors for transitional cell carcinoma, cystoscopy should be performed regardless of cytology results 1
• If cytology shows malignant or atypical/suspicious cells, cystoscopy is required even in lower-risk patients 1

Glomerular vs. Non-Glomerular Differentiation

Indicators of glomerular origin requiring nephrology referral 2, 5:

• Dysmorphic RBCs >80% 2
• Red cell casts in urinary sediment 2
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g for three specimens) 2
• Elevated serum creatinine or declining renal function 2
• Tea-colored urine appearance 2
• Associated hypertension 2, 5

Follow-Up Protocol for Negative Initial Evaluation

• If all investigations are negative but hematuria persists, repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1, 5
• Consider comprehensive re-evaluation with repeat cystoscopy and imaging within 3-5 years for persistent or recurrent hematuria, particularly in high-risk populations 5
• Immediate re-evaluation is warranted if gross hematuria develops, significant increase in degree of microscopic hematuria occurs, or new urologic symptoms appear 5

Critical Pitfalls to Avoid

• Never defer evaluation in patients on anticoagulation or antiplatelet therapy, as these medications may unmask underlying pathology but do not cause hematuria; malignancy risk is similar regardless of anticoagulation status 2, 5
• Gross hematuria always requires urgent urologic referral even if self-limited, as it carries a 30-40% association with malignancy 2, 6
• Do not attribute hematuria solely to benign prostatic hyperplasia without completing full evaluation in high-risk patients 2
• Findings of 0-2 RBCs/HPF fall within normal range and do not warrant extensive urologic workup 2
• After treating UTI, documented microscopic confirmation of hematuria resolution is required—do not stop at symptom resolution alone 5