What is the appropriate workup for an adult patient with no significant past medical history presenting with hematuria?

Workup for Hematuria in Adults

Confirm true hematuria first with microscopic urinalysis showing ≥3 RBCs per high-power field on at least two of three properly collected clean-catch midstream urine specimens before initiating any workup, as dipstick testing alone has only 65-99% specificity and can produce false positives. 1

Step 1: Confirm True Hematuria and Exclude Transient Causes

• Verify microscopic hematuria (≥3 RBCs/HPF) on at least two of three properly collected specimens 1, 2
• If history suggests benign transient causes (vigorous exercise, sexual activity, menstruation, minor trauma), repeat urinalysis 48 hours after cessation of the activity 3
• No further evaluation needed if hematuria resolves after eliminating transient causes 3
• In women, perform urethral and vaginal examination to exclude local contamination; obtain catheterized specimen if clean-catch is unreliable 3

Step 2: Initial Laboratory Evaluation

• Complete urinalysis with microscopy examining for:

  • Dysmorphic RBCs (>80% suggests glomerular origin) 1, 4
  • Red cell casts (pathognomonic for glomerular disease) 1, 4
  • Degree of proteinuria (>0.5 g/g protein-to-creatinine ratio suggests renal parenchymal disease) 1
  • White blood cells and bacteria (suggests infection) 3, 4

• Serum creatinine to assess renal function 3, 1

• Urine culture if infection suspected, preferably before antibiotics 1, 2

  • If positive, treat appropriately and repeat urinalysis 6 weeks after treatment 3, 2
  • If hematuria resolves with infection treatment, no additional evaluation necessary 3
  • If hematuria persists after treating infection, proceed with full urologic evaluation 1

Step 3: Risk Stratification for Malignancy

High-risk features requiring immediate complete urologic evaluation: 1, 2, 4

• Any episode of gross hematuria (30-40% malignancy risk) 1, 4
• Age ≥60 years (males) or ≥60 years (females) 1
• Smoking history >30 pack-years 1, 2
• Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 1, 4
• History of gross hematuria (even if currently microscopic) 1
• Irritative voiding symptoms without infection 1

• 25 RBCs/HPF on microscopy 1

Intermediate-risk features: 1

• Age 40-59 years (males) or age <60 years (females)
• Smoking history 10-30 pack-years
• 11-25 RBCs/HPF

Low-risk features: 1

• Age <40 years (males) or <60 years (females)
• Never smoker or <10 pack-years
• 3-10 RBCs/HPF

Step 4: Determine Glomerular vs. Non-Glomerular Source

Glomerular indicators (nephrology referral needed): 1, 4

• Tea-colored or cola-colored urine 1, 4
• Dysmorphic RBCs >80% 1, 4
• Red cell casts (pathognomonic) 1, 4
• Significant proteinuria (protein-to-creatinine ratio >0.5 g/g) 1
• Elevated serum creatinine or declining renal function 1
• Hypertension with hematuria 1

If glomerular features present:

• Refer to nephrology for additional workup (complement levels C3/C4, ANA, ANCA, renal biopsy consideration) 1
• Still complete urologic evaluation, as malignancy can coexist with medical renal disease 1

Step 5: Complete Urologic Evaluation (for Non-Glomerular or High-Risk Patients)

Upper Tract Imaging

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

• Includes unenhanced, nephrographic phase, and excretory phase 1
• Detects renal cell carcinoma, transitional cell carcinoma, and urolithiasis 3, 1

Alternative imaging if CT contraindicated:

• MR urography for patients with renal insufficiency or contrast allergy 1
• Renal ultrasound with retrograde pyelography (less optimal, insufficient alone) 3, 1

Lower Tract Evaluation

Cystoscopy is mandatory for: 1, 2

• All patients with gross hematuria 1, 2
• All patients ≥40 years with microscopic hematuria 2
• Microscopic hematuria patients with high-risk features 1, 2

Flexible cystoscopy preferred over rigid cystoscopy (less pain, equivalent or superior diagnostic accuracy) 1

Urine Cytology

Voided urine cytology recommended for: 3, 1

• All patients with risk factors for transitional cell carcinoma 3
• High-risk patients (age >60, smoking history, occupational exposure) 1
• Useful adjunct to cystoscopy, especially for detecting carcinoma in situ 3

Step 6: Follow-Up Protocol

If initial workup negative but hematuria persists: 1, 2

• Repeat urinalysis, voided urine cytology, and blood pressure at 6,12,24, and 36 months 1, 2
• After two consecutive negative annual urinalyses, no further testing needed 1
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 1

Immediate re-evaluation warranted if: 1

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

Critical Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 4, 5
• Never defer evaluation due to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria 1, 4
• Never rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBCs/HPF 1, 2
• Never attribute hematuria to urinary tract infection without confirming resolution after treatment—persistent hematuria requires full evaluation 1, 2
• Never assume benign prostatic hyperplasia explains hematuria without excluding concurrent malignancy 1
• Glomerular features do not eliminate need for urologic evaluation—malignancy can coexist with renal disease 1