What are the next steps for a 58-year-old female with persistent kidney pain and hematuria (blood in urine) for over one week, despite normal laboratory tests and urinalysis (UA) results?

Imaging Evaluation for Persistent Hematuria with Normal Initial Workup

This 58-year-old woman with persistent kidney pain and hematuria for over one week, despite normal labs and urinalysis, requires immediate upper tract imaging with multiphasic CT urography and cystoscopy to exclude malignancy and other serious urologic pathology. 1, 2, 3

Critical Context: "Normal" UA Does Not Mean No Hematuria

The statement that UA is "normal" requires clarification, as this directly determines the entire diagnostic pathway:

• If microscopic examination truly shows 0-2 RBCs/HPF: This falls within normal limits and technically does not constitute hematuria requiring urologic workup 1
• However, the clinical presentation of visible kidney pain with reported "hematuria" for >1 week strongly suggests either:
  • Gross hematuria was present but not captured on this particular UA specimen
  • Intermittent hematuria that resolved by time of testing
  • Dipstick-positive result that wasn't confirmed microscopically 1, 3

Given the symptomatic presentation with flank pain, this patient requires full urologic evaluation regardless of a single negative UA. 1, 2

Why This Patient Cannot Be Dismissed

High-Risk Features Present

This patient has multiple concerning characteristics that mandate complete evaluation:

• Age 58 years (female): Places her in intermediate-to-high risk category for urothelial malignancy 1, 2
• Symptomatic presentation: Kidney pain with hematuria suggests structural pathology (nephrolithiasis, renal mass, or urothelial tumor) rather than benign transient causes 1, 3
• Persistent symptoms >1 week: Duration excludes transient benign causes like exercise, trauma, or viral illness 2, 3
• Gross hematuria carries 30-40% malignancy risk: If patient reports visible blood, this alone mandates urgent urologic referral even if self-limited 1, 2

Critical Pitfall to Avoid

Never attribute hematuria to a single negative UA when clinical suspicion is high. Hematuria can be intermittent, and malignancies (particularly urothelial carcinomas) can present with episodic bleeding. 1, 2 A history of gross hematuria significantly increases cancer risk (odds ratio 7.2) and requires complete evaluation regardless of subsequent negative testing. 2

Recommended Diagnostic Algorithm

Step 1: Confirm True Hematuria Status

• Repeat urinalysis with microscopic examination to document ≥3 RBCs/HPF on at least one properly collected clean-catch midstream specimen 1, 3
• Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular source), red cell casts (pathognomonic for glomerular disease), and degree of proteinuria 1, 2, 3
• Obtain urine culture to definitively exclude urinary tract infection as cause 1, 2, 3

Step 2: Assess for Glomerular vs. Non-Glomerular Source

Glomerular indicators (if present, nephrology referral indicated):

• Dysmorphic RBCs >80% 1, 2
• Red cell casts 1, 2
• Significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.5) 1, 2
• Elevated serum creatinine or declining renal function 1, 2
• Tea-colored or cola-colored urine 1

Non-glomerular indicators (urologic evaluation required):

• Normal-appearing RBCs (>80% non-dysmorphic) 1
• Bright red blood 1
• Flank pain (suggests nephrolithiasis, renal mass, or pyelonephritis) 1
• Minimal or no proteinuria 1, 2

Step 3: Complete Urologic Evaluation (Required for This Patient)

Upper tract imaging:

• Multiphasic CT urography is the preferred modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis in adults with hematuria 1, 2, 3
• CT urography provides comprehensive evaluation of kidneys, ureters, and bladder in multiple phases 1, 3
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation and misses small renal masses and urothelial tumors 1

Lower tract evaluation:

• Cystoscopy is mandatory for all patients ≥40 years with hematuria to detect bladder tumors and carcinoma in situ 1, 2, 3
• Flexible cystoscopy is preferred over rigid cystoscopy (less pain, equivalent diagnostic accuracy) 1, 3

Laboratory evaluation:

• Serum creatinine to assess renal function 1, 2, 3
• Complete metabolic panel 1
• Urine cytology in high-risk patients (age >40, smoking history, occupational exposures, irritative voiding symptoms) 1, 3

Special Considerations for Symptomatic Presentation

Kidney Pain with Hematuria Differential

The combination of flank pain and hematuria narrows the differential diagnosis:

Most likely etiologies requiring imaging:

• Nephrolithiasis: Most common cause of painful hematuria; CT urography will detect stones with high sensitivity 1, 4
• Renal cell carcinoma: Can present with flank pain, hematuria, and palpable mass (classic triad, though rarely all present) 1, 3
• Urothelial carcinoma of renal pelvis or ureter: Can cause obstruction and flank pain 1, 3
• Renal infarction or papillary necrosis: Less common but serious causes 1

Why "Normal Labs" Don't Exclude Serious Pathology

• Normal serum creatinine doesn't exclude renal masses, stones, or urothelial tumors 1, 3
• Normal inflammatory markers don't exclude malignancy 5
• A single negative UA doesn't exclude intermittent bleeding from tumor or stone 1, 2

Follow-Up Strategy If Initial Workup Negative

If CT urography and cystoscopy are negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1, 2, 3
• Immediate re-evaluation warranted if:
  • Gross hematuria develops 1, 2
  • Significant increase in degree of microscopic hematuria 1, 2
  • New urologic symptoms appear 1, 2
  • Development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2
• Consider repeat cystoscopy and imaging within 3-5 years for persistent or recurrent hematuria, particularly in high-risk populations 2

When to Refer to Nephrology

Nephrology referral is indicated if:

• Dysmorphic RBCs >80% with or without red cell casts 1, 2, 3
• Proteinuria >500 mg/24 hours 1, 2, 3
• Elevated serum creatinine or declining renal function 1, 2
• Hypertension with persistent hematuria 1, 2

Both urologic and nephrologic evaluation may be needed simultaneously if features of both glomerular and non-glomerular disease are present. 2