What is the appropriate management for a patient with hematuria and leukocyturia, potentially indicating a urinary tract infection or other kidney and urinary tract disorders?

Management of Urine with High Erythrocytes and Leukocytes

When both hematuria and leukocyturia are present, you must first rule out urinary tract infection with urine culture; if infection is confirmed, treat appropriately and repeat urinalysis 6 weeks after treatment completion to determine if hematuria persists—only then can you decide whether full urologic evaluation is needed. 1

Initial Diagnostic Approach

Confirm True Hematuria and Assess for Infection

• Verify microscopic hematuria with ≥3 red blood cells per high-power field (RBC/HPF) on properly collected clean-catch midstream urine specimens, as dipstick testing alone has limited specificity (65-99%) and should never be relied upon without microscopic confirmation. 2, 3

• Obtain urine culture immediately if infection is suspected based on the presence of leukocyturia, before initiating any antibiotic therapy. 1, 4

• If urinary tract infection is confirmed by positive culture, treat with appropriate antibiotics (such as trimethoprim-sulfamethoxazole for susceptible organisms including E. coli, Klebsiella, Enterobacter, Proteus mirabilis, and Proteus vulgaris). 5

• Repeat urinalysis 6 weeks after completing antibiotic treatment to confirm resolution of hematuria—this is a critical safety checkpoint that prevents delayed cancer diagnosis, as approximately 3% of patients with microscopic hematuria harbor genitourinary malignancy. 1

Exclude Benign Transient Causes

• Rule out menstruation, vigorous exercise, sexual activity, trauma, or viral illness as potential benign causes of hematuria. 2, 1

• If a benign cause is suspected, repeat urinalysis 48 hours after cessation of the potential cause (e.g., after menstruation ends or 48 hours after exercise). 1

• If hematuria resolves after treating infection or removing benign cause, no additional evaluation is necessary. 1

Risk Stratification for Persistent Hematuria

If hematuria persists after treating infection or excluding benign causes, stratify the patient's risk for urologic malignancy:

High-Risk Features (Require Immediate Complete Urologic Evaluation)

• Age ≥60 years (both males and females) 3, 1
• Smoking history >30 pack-years 3, 1
• >25 RBCs per high-power field 3, 1
• Any history of gross hematuria (even if self-limited, as this carries an odds ratio of 7.2 for urologic cancer) 2, 1
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 3, 1
• Irritative voiding symptoms without infection 1, 4

Intermediate-Risk Features

• Women age 50-59 years or men age 40-59 years 1
• Smoking history 10-30 pack-years 1
• 11-25 RBCs per high-power field 1

Low-Risk Features

• Women age <50 years or men age <40 years 1
• Never smoker or <10 pack-years 1
• 3-10 RBCs per high-power field on single urinalysis 1
• No additional risk factors for urothelial cancer 1

Distinguish Glomerular from Non-Glomerular Sources

Before proceeding with urologic evaluation, assess for signs of glomerular (kidney parenchymal) disease:

Indicators of Glomerular Disease (Require Nephrology Referral)

• Significant proteinuria >500-1000 mg/24 hours (or protein-to-creatinine ratio >0.2 g/g) 3, 1, 4
• Dysmorphic RBCs >80% on microscopic examination with phase contrast microscopy 3, 1, 4
• Red blood cell casts (pathognomonic for glomerular disease) 3, 1, 4
• Elevated serum creatinine or declining renal function 3, 1
• Tea-colored or cola-colored urine (suggests glomerular source) 4
• Hypertension accompanying hematuria 1, 4

Important caveat: The presence of glomerular features does not eliminate the need for urologic evaluation—both evaluations should be completed, as malignancy can coexist with medical renal disease. 4

Indicators of Non-Glomerular (Urologic) Source

• Normal-appearing RBCs without casts 3
• Absence of significant proteinuria (trace or <500 mg/24 hours) 4
• Normal serum creatinine 3
• Bright red blood in urine (suggests lower urinary tract bleeding) 4

Complete Urologic Evaluation for High-Risk or Intermediate-Risk Patients

Mandatory Components

• Multiphasic CT urography is the preferred imaging modality to detect renal cell carcinoma, transitional cell carcinoma, urolithiasis, and upper tract abnormalities (includes unenhanced, nephrographic phase, and excretory phase images). 3, 1, 4

• Cystoscopy is mandatory for all high-risk patients and intermediate-risk patients (through shared decision-making) to visualize bladder mucosa, urethra, and ureteral orifices for transitional cell carcinoma. 3, 1, 4

• Flexible cystoscopy is preferred over rigid cystoscopy as it causes less pain, has fewer post-procedure symptoms, and demonstrates equivalent or superior diagnostic accuracy. 1, 4

Additional Laboratory Testing

• Serum creatinine, BUN, and complete metabolic panel to assess renal function 1, 4
• Complete urinalysis with microscopy to examine for dysmorphic RBCs and casts 1, 4
• Voided urine cytology may be considered in high-risk patients (age ≥60, smoking history, irritative voiding symptoms) to detect high-grade urothelial carcinomas and carcinoma in situ 3, 1

Follow-Up Protocol for Negative Initial Evaluation

If the complete urologic evaluation is negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1, 4

• Consider repeat complete evaluation within 3-5 years for persistent or recurrent hematuria, particularly in high-risk populations 1

• After two consecutive negative annual urinalyses, no further testing for asymptomatic microhematuria is necessary 4

Immediate Re-Evaluation is Warranted If:

• Gross hematuria develops (30-40% malignancy risk) 1, 4
• Significant increase in degree of microscopic hematuria 1
• New urologic symptoms appear (flank pain, dysuria, irritative voiding symptoms) 1
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1

Critical Pitfalls to Avoid

• Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves, and evaluation must proceed regardless. 2, 3, 4

• Never ignore gross hematuria, even if self-limited—it carries a 30-40% risk of malignancy and requires urgent urologic referral. 2, 1, 4

• Do not prescribe additional courses of antibiotics for persistent hematuria after appropriate treatment—this delays cancer diagnosis and provides false reassurance. 4

• Do not treat asymptomatic bacteriuria—there is no benefit and high-quality evidence of harm including antibiotic resistance and Clostridioides difficile infection. 4

• Document microscopic confirmation of resolution of hematuria—do not stop at symptom resolution alone. 1