What are the next steps in managing a patient with hematuria and leukocytosis?

Management of Hematuria with Leukocytosis

The immediate priority is to rule out urinary tract infection with urine culture, then proceed with risk-stratified hematuria evaluation based on patient age, smoking history, and degree of hematuria—while simultaneously investigating the leukocytosis for infectious, inflammatory, or hematologic causes. 1, 2

Initial Diagnostic Steps

Confirm True Hematuria

• Verify microscopic hematuria with ≥3 RBCs per high-power field on properly collected clean-catch midstream urine specimen 1, 3
• Do not rely solely on dipstick results, which have only 65-99% specificity and can produce false positives 1, 3
• Repeat urinalysis on two of three specimens if initial finding shows 3-10 RBCs/HPF in low-risk patients 4

Address the Leukocytosis

• Obtain complete blood count with differential to characterize the white blood cell elevation and identify cell types 2
• Do NOT treat with antibiotics empirically for asymptomatic pyuria—this causes antibiotic resistance and delays cancer diagnosis 1
• Obtain urine culture if urinary tract infection is suspected based on symptoms (dysuria, urgency, frequency, fever) 1, 3
• If urine culture is positive, treat appropriately and repeat urinalysis 6 weeks after completing antibiotics to confirm hematuria resolution 3

Risk Stratification for Hematuria

Use the 2025 AUA/SUFU risk stratification system to determine evaluation intensity 4, 5:

High-Risk Features (Require Full Urologic Evaluation)

• Age ≥60 years (men or women) 4
• Smoking history >30 pack-years 4

• 25 RBCs/HPF on single urinalysis 4

• History of gross hematuria 4
• Occupational exposure to benzenes or aromatic amines 1, 3
• Irritative voiding symptoms without infection 1

Intermediate-Risk Features

• Women age 50-59 years; Men age 40-59 years 4
• Smoking history 10-30 pack-years 4
• 11-25 RBCs/HPF on single urinalysis 4

Low-Risk Features

• Women age <50 years; Men age <40 years 4
• Never smoker or <10 pack-years 4
• 3-10 RBCs/HPF on single urinalysis 4

Complete Urologic Evaluation (for Intermediate/High-Risk)

Upper Tract Imaging

• Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 3, 5
• Include unenhanced, nephrographic phase, and excretory phase images 1
• If CT is contraindicated (renal insufficiency, contrast allergy), use MR urography or renal ultrasound with retrograde pyelography 1

Lower Tract Evaluation

• Cystoscopy is mandatory for all intermediate- and high-risk patients to visualize bladder mucosa, urethra, and ureteral orifices 1, 3, 5
• Flexible cystoscopy is preferred over rigid cystoscopy—causes less pain with equivalent or superior diagnostic accuracy 1, 3

Laboratory Testing

• Serum creatinine to assess renal function 1, 3, 5
• Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular source) and red cell casts (pathognomonic for glomerular disease) 1, 3, 5
• Check for proteinuria—significant proteinuria (>500 mg/24 hours) suggests renal parenchymal disease 1, 3

Evaluating the Leukocytosis

Benign Causes to Consider

• Infection (most common cause)—correlate with clinical symptoms and urine culture results 2, 6
• Physical or emotional stress, recent surgery, exercise, or trauma 2, 6
• Medications: corticosteroids, lithium, beta agonists 6
• Smoking, obesity, chronic inflammatory conditions 2
• Asplenia 2

Red Flags for Hematologic Malignancy

• Fever, unintentional weight loss, bruising, or fatigue 2
• Extremely elevated WBC count (>100,000/mm³ represents medical emergency) 6
• Concurrent abnormalities in red blood cell or platelet counts 6
• Hepatosplenomegaly or lymphadenopathy 6

When to Refer to Hematology/Oncology

• If malignancy cannot be excluded or another more likely cause is not identified, refer to hematology/oncology 2
• Primary bone marrow disorders (acute leukemias, chronic leukemias, myeloproliferative disorders) should be suspected with extreme elevations or concurrent cytopenias 6

Special Consideration: Glomerular vs. Non-Glomerular Source

Indicators of Glomerular Disease

• Tea-colored or cola-colored urine 1, 3
• Dysmorphic RBCs >80% on phase contrast microscopy 1, 3, 5
• Red cell casts in urinary sediment 1, 3, 5
• Significant proteinuria (>500 mg/24 hours) 1, 3, 5
• Elevated serum creatinine 1, 3, 5
• Associated hypertension 1, 3

Nephrology Referral Indications

• Persistent hematuria with dysmorphic RBCs >80% or red cell casts 1, 3, 5
• Proteinuria >500 mg/24 hours 1, 3, 5
• Elevated or rising serum creatinine 1, 3, 5
• Development of hypertension with persistent hematuria 1, 3, 5

Critical Pitfalls to Avoid

• Never attribute hematuria to anticoagulation or antiplatelet therapy alone—these medications may unmask underlying pathology but do not cause hematuria themselves 1, 3
• Never treat asymptomatic bacteriuria—this leads to antibiotic resistance, Clostridioides difficile infection, and delays cancer diagnosis 1
• Never ignore gross hematuria, even if self-limited—it carries a 30-40% malignancy risk and requires urgent urologic referral 1, 3
• Do not obtain urinary cytology or urine-based molecular markers in initial evaluation—not recommended by current guidelines 1
• Do not discharge patients with persistent microscopic hematuria after UTI treatment without repeat urinalysis at 6 weeks—approximately 3% harbor genitourinary malignancy 3

Follow-Up Protocol

If Initial Workup is Negative

• Repeat urinalysis at 6,12,24, and 36 months 4, 1, 3, 5
• Monitor blood pressure at each visit 4, 1, 3, 5
• Engage in shared decision-making regarding need for additional evaluation if hematuria persists 4

Immediate Re-Evaluation Required If:

• Gross hematuria develops 4
• Significant increase in degree of microscopic hematuria 4
• New urologic symptoms appear 4
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 4, 1