What is the appropriate workup for a patient with a history of cholecystectomy (gallbladder removal) presenting with hematuria (blood in urine)?

Hematuria Workup

For a patient with hematuria (regardless of prior cholecystectomy, which is irrelevant to the workup), proceed with risk stratification followed by cystoscopy and multiphasic CT urography for intermediate- and high-risk patients, while low-risk patients may be managed with less aggressive imaging.

Initial Confirmation and Risk Stratification

• Confirm true hematuria by documenting ≥3 red blood cells per high-power field on microscopic urinalysis from at least two of three properly collected clean-catch midstream specimens 1, 2
• Dipstick positivity alone is insufficient (specificity only 65-99%) and should never trigger extensive workup without microscopic confirmation 2

Risk stratification based on AUA criteria 2:

High-risk features:

• Age ≥60 years 2
• Smoking history >30 pack-years 2

• 25 RBC/HPF on urinalysis 2

• History of gross hematuria 2
• Occupational exposure to benzenes or aromatic amines 2
• History of pelvic irradiation 1
• Irritative voiding symptoms 1, 2

Intermediate-risk features:

• Men age 40-59 years 2
• 10-30 pack-years smoking 2
• 11-25 RBC/HPF 2

Low-risk features:

• Men age <40 years 2
• Never smoker or <10 pack-years 2
• 3-10 RBC/HPF 2

Exclude Glomerular Disease First

Before proceeding with urologic evaluation, assess for glomerular sources 2:

• Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular origin) and red blood cell casts (pathognomonic for glomerular disease) 3, 2
• Check for proteinuria using spot urine protein-to-creatinine ratio (normal <0.2 g/g) 3
• Measure serum creatinine and complete metabolic panel 1, 2
• Tea-colored or cola-colored urine strongly suggests glomerular disease 4

If glomerular disease is suspected (dysmorphic RBCs, red cell casts, significant proteinuria, or elevated creatinine), refer to nephrology in addition to completing urologic evaluation 2

Complete Urologic Evaluation for Non-Glomerular Hematuria

Imaging

For intermediate- and high-risk patients:

• Multiphasic CT urography (CTU) is the gold standard imaging modality 1, 2
• CTU must include three phases: unenhanced, nephrographic phase with IV contrast, and excretory phase to evaluate renal parenchyma and urothelium 1
• CTU has the highest sensitivity and specificity for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 2

Alternative imaging options (less optimal):

• MR urography if CT contraindicated due to renal insufficiency or contrast allergy 2
• Renal ultrasound alone is insufficient and only acceptable for low-risk patients 2
• Ultrasound combined with IVU is widely used but presents significant risk for missed diagnoses 1

Cystoscopy

• White light cystoscopy is mandatory for all patients ≥40 years old with microscopic hematuria and all patients with gross hematuria, regardless of age 1, 2
• Cystoscopy should be performed on all patients with risk factors (irritative voiding symptoms, tobacco use, chemical exposures) regardless of age 1
• Flexible cystoscopy is preferred over rigid cystoscopy due to less pain and equivalent or superior diagnostic accuracy 2
• Cystoscopy remains essential even with negative cytology, as it is the gold standard for detecting bladder tumors and carcinoma in situ 2

Laboratory Tests

• Urine culture if infection suspected, preferably before antibiotic therapy 3, 4
• Serum creatinine to assess renal function 2
• Spot urine calcium-to-creatinine ratio to evaluate for hypercalciuria 3
• Urine cytology is NOT recommended as part of routine microscopic hematuria evaluation due to inadequate sensitivity 2

Critical Pitfalls to Avoid

• Never attribute hematuria to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves 2, 4
• Never ignore gross hematuria, even if self-limited—it carries a 30-40% malignancy risk and mandates urgent urologic referral 3, 4
• Do not stop evaluation after negative cytology and culture alone—these tests lack sufficient sensitivity to exclude malignancy 2
• Do not attribute hematuria solely to benign conditions (like BPH) without completing full urologic evaluation, as approximately 3% of patients with microscopic hematuria harbor genitourinary malignancy 2
• Prior cholecystectomy is completely irrelevant to hematuria workup and should not influence the evaluation 5

Follow-Up Protocol for Negative Initial Evaluation

If cystoscopy and imaging are negative but hematuria persists 3, 2:

• Repeat urinalysis at 6,12,24, and 36 months 3, 2
• Monitor blood pressure at each visit 3, 2
• Consider repeat cystoscopy and imaging within 3-5 years for persistent or recurrent hematuria 2

Immediate re-evaluation is required if 2:

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

Special Considerations

• Exercise-induced hematuria is transient and resolves with rest, but other causes must be excluded first 3
• Menstruation can contaminate urine samples in women—ensure proper specimen collection 4
• Less than 1% of patients with negative thorough workup manifest serious disease during 14 years of follow-up, reinforcing the importance of completing initial workup 1
• In most patients with asymptomatic microscopic hematuria, a cause is never found (idiopathic microscopic hematuria accounts for approximately 80% of cases) 3