What is the recommended workup for a patient presenting with microhematuria?

Microhematuria Workup

Confirm True Microhematuria First

Before initiating any workup, confirm microscopic hematuria by demonstrating ≥3 red blood cells per high-power field (RBC/HPF) on microscopic urinalysis in at least two of three properly collected clean-catch midstream urine specimens. 1, 2 Dipstick positivity alone has limited specificity (65-99%) and should never trigger imaging or invasive procedures without microscopic confirmation. 3

Initial Risk Stratification

Once confirmed, stratify patients into risk categories based on the following factors 1, 3, 2:

High-Risk Features (require complete urologic evaluation):

• Age ≥40 years (men) or ≥60 years (women) 4, 1
• Smoking history >30 pack-years 1, 3
• Occupational exposure to chemicals (benzenes, aromatic amines) 4, 3
• History of gross hematuria 3
• Irritative voiding symptoms without infection 4, 3
• Male sex 3
• ≥25 RBC/HPF 3

Important: Anticoagulation therapy does NOT explain hematuria and should never defer evaluation—these medications may unmask underlying pathology. 4, 3

Determine Glomerular vs. Non-Glomerular Source

Examine urinary sediment for the following 1, 3, 2:

Glomerular indicators (refer to nephrology):

• 80% dysmorphic RBCs 3, 2

• Red blood cell casts (pathognomonic for glomerular disease) 3
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g) 3
• Elevated serum creatinine or declining renal function 1, 3
• Tea-colored urine 3

If glomerular source suspected: Immediate nephrology referral for evaluation of primary renal disease, which may include complement levels (C3, C4), ANA, ANCA testing, and consideration of renal biopsy. 3, 2 This does NOT preclude urologic evaluation—both can coexist. 4

Complete Urologic Evaluation for Non-Glomerular Hematuria

Laboratory Testing

• Serum creatinine, BUN, complete metabolic panel 4, 3, 2
• Urine culture if infection suspected (preferably before antibiotics) 3
• Voided urine cytology for high-risk patients 3, 2

Imaging of Upper Urinary Tract

Multiphasic CT urography is the preferred imaging modality for intermediate- and high-risk patients to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis. 3, 2 Renal ultrasound alone is insufficient for comprehensive upper tract evaluation. 3

Cystoscopy

Cystoscopy is mandatory for all patients ≥35 years old with confirmed microhematuria. 4, 1 For patients <35 years, cystoscopy should be performed if any risk factors are present (smoking, chemical exposure, irritative voiding symptoms, history of urologic disorders). 4, 1 Flexible cystoscopy is preferred as it causes less pain with equivalent diagnostic accuracy. 3

Special Clinical Scenarios

Urinary tract infection present: Treat with appropriate antibiotics, then repeat urinalysis 6 weeks after treatment to confirm resolution. 1 If hematuria persists, proceed with full evaluation—infection does not exclude malignancy. 1

Benign prostatic hyperplasia: BPH can cause hematuria but does NOT exclude concurrent malignancy. 3 Complete evaluation is still required.

Resolved hematuria at 3-month follow-up: If initial workup (cystoscopy and renal ultrasound) was negative and hematuria has resolved, further imaging may not be necessary. 5 However, patients with risk factors should still be monitored.

Follow-Up Protocol for Negative Initial Evaluation

If the complete workup is negative but microhematuria persists 4, 1, 2:

• Repeat urinalysis at 6,12,24, and 36 months
• Monitor blood pressure at each visit
• Consider repeat evaluation within 3-5 years for persistent or recurrent microhematuria 4

Immediate re-evaluation warranted if:

• Gross hematuria develops 3
• Substantial increase in degree of microhematuria 4
• New urologic symptoms appear 4
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 3, 2

Critical Pitfalls to Avoid

• Never attribute hematuria to medications alone (including anticoagulants, Cialis, or other drugs)—always investigate for underlying pathology. 4, 3
• Gross hematuria has 30-40% association with malignancy and requires urgent urologic referral even if self-limited. 3
• Do not skip cystoscopy in patients ≥35 years—bladder cancer is the most frequently diagnosed malignancy in hematuria cases. 4, 3
• Dipstick alone is never sufficient—always confirm with microscopic urinalysis showing ≥3 RBC/HPF. 1, 3