What are the appropriate next steps for a 69‑year‑old woman with painless hematuria and pyuria, negative urine culture, and normal serum creatinine?

Urgent Urologic Evaluation Required

This 69-year-old woman with persistent hematuria and pyuria despite negative urine culture requires immediate urologic referral for cystoscopy and upper tract imaging (CT urography) to exclude malignancy—her age and sex place her at intermediate-to-high risk for urothelial carcinoma, and the 30-40% malignancy risk associated with hematuria mandates complete evaluation regardless of the absence of infection. 1

Immediate Next Steps

1. Confirm True Microscopic Hematuria

• Verify that microscopic urinalysis shows ≥3 red blood cells per high-power field (RBC/HPF) on at least two of three properly collected clean-catch midstream specimens before proceeding with extensive workup 1, 2
• Dipstick testing alone has only 65-99% specificity and can produce false positives from contamination or menstrual blood 1

2. Complete Urologic Evaluation (Mandatory)

Upper Tract Imaging

• Multiphasic CT urography is the preferred imaging modality, comprising unenhanced, nephrographic, and excretory phases to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 3
• This is superior to renal ultrasound alone, which is insufficient for comprehensive upper tract evaluation 1

Lower Tract Evaluation

• Flexible cystoscopy is mandatory for all women ≥60 years with microscopic hematuria to visualize bladder mucosa, urethra, and ureteral orifices 1, 2
• Flexible cystoscopy causes less pain than rigid cystoscopy while providing equivalent or superior diagnostic accuracy 1

Additional Testing

• Voided urine cytology should be obtained given her high-risk status (age ≥60 years) to detect high-grade urothelial carcinomas and carcinoma in situ 1

Why Infection Does Not Explain This Case

• Pyuria without positive culture does not exclude malignancy—the combination of sterile pyuria and hematuria is particularly concerning for urothelial carcinoma or other urologic pathology 1
• The American Urological Association explicitly states that pyuria should never delay complete urologic evaluation in patients with hematuria 1
• Do not prescribe empiric antibiotics—this delays cancer diagnosis and provides false reassurance 1

Risk Stratification

This patient has multiple high-risk features for malignancy:

• Age ≥60 years (women in this age group are intermediate-to-high risk) 1
• Persistent hematuria despite negative culture 1
• Normal creatinine (1.01) argues against glomerular disease as the primary cause 1

The American Urological Association guidelines classify her as requiring full urologic evaluation with both cystoscopy and CT urography 1, 2

Distinguishing Glomerular from Non-Glomerular Sources

Assess for Glomerular Features

• Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular origin) and red blood cell casts (pathognomonic for glomerular disease) 1, 3
• Check for significant proteinuria using spot urine protein-to-creatinine ratio—values >0.5 g/g strongly suggest renal parenchymal disease 1
• The absence of proteinuria, normal creatinine, and lack of dysmorphic RBCs or casts point toward a non-glomerular (urologic) source 1, 4

If Glomerular Features Are Present

• Nephrology referral is indicated for significant proteinuria, dysmorphic RBCs >80%, red cell casts, or elevated serum creatinine 1, 5
• However, glomerular features do not eliminate the need for urologic evaluation—malignancy can coexist with medical renal disease 1

Common Pitfalls to Avoid

• Never attribute hematuria to "sterile pyuria" alone—this combination is a red flag for urothelial carcinoma 1
• Do not delay evaluation waiting for infection to "declare itself"—a negative culture after appropriate collection effectively rules out UTI 1
• Do not assume benign cause based on normal creatinine—renal function does not predict urologic malignancy risk 1, 3
• Never ignore hematuria in elderly women—bladder cancer detection rates are substantial in this population, and delays beyond 9 months are associated with worse cancer-specific survival 1

Follow-Up Protocol If Initial Workup Is Negative

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1
• Immediate re-evaluation is warranted if gross hematuria develops, significant increase in microscopic hematuria occurs, new urologic symptoms appear, or development of hypertension or proteinuria 1
• After two consecutive negative annual urinalyses, no further testing is necessary 1

Summary Algorithm

1. Confirm microscopic hematuria (≥3 RBC/HPF on ≥2 specimens) 1, 2
2. Examine urinary sediment for dysmorphic RBCs, casts, and proteinuria 1
3. Refer urgently to urology for cystoscopy and CT urography 1, 2
4. Obtain urine cytology given age ≥60 years 1
5. Consider nephrology referral only if glomerular features emerge (proteinuria, dysmorphic RBCs, casts, elevated creatinine) 1, 5
6. Do not prescribe antibiotics or delay evaluation 1