What is the differential diagnosis (DD) of hematuria and what labs are needed?

Differential Diagnosis of Hematuria and Required Laboratory Tests

The differential diagnosis of hematuria is broad, ranging from benign causes to serious urologic and renal diseases, requiring a systematic evaluation with specific laboratory tests to determine the source and etiology of bleeding.

Initial Assessment of Hematuria

Classification of Hematuria

• Microscopic hematuria: Defined as ≥3 red blood cells per high-power field on microscopic evaluation of 2 of 3 properly collected urine specimens 1
• Macroscopic (gross) hematuria: Visible blood in urine, carries >10% risk of malignancy 2

Key Distinction: Glomerular vs. Non-Glomerular Source

Determining the source of bleeding is the first critical step:

Glomerular Source Indicators:

• Dysmorphic RBCs (>80% indicates glomerular source) 1
• Red blood cell casts (pathognomonic for glomerular bleeding) 1
• Significant proteinuria (>500-1000 mg/24 hours) 1
• Tea-colored urine 1

Non-Glomerular Source Indicators:

• Normal-shaped RBCs (>80% indicates lower tract bleeding) 1
• Absence of proteinuria and casts 1
• Bright red or pink urine 1

Differential Diagnosis

Glomerular Causes

1. Systemic diseases with renal involvement:

   • Lupus erythematosus
   • Vasculitis
   • Infections (hepatitis, endocarditis)
   • Henoch-Schönlein purpura 1

2. Primary renal diseases:

   • IgA nephropathy (Berger's disease)
   • Membranoproliferative glomerulonephritis
   • Crescentic glomerulonephritis
   • Alport syndrome 1
   • Thin basement membrane nephropathy 1

Non-Glomerular Causes

1. Urologic conditions:

   • Urinary tract infection
   • Urolithiasis (kidney stones)
   • Malignancy (bladder cancer, renal cell carcinoma, upper tract urothelial carcinoma) 3
   • Benign prostatic hyperplasia 2
   • Trauma 1

2. Other causes:

   • Drug-induced hematuria (especially analgesics) 4
   • Exercise-induced hematuria 1
   • Hypercalciuria 1
   • Coagulopathies (sickle cell disease, hemophilia) 1
   • Factitious hematuria (food dyes, medications) 1

Required Laboratory Tests

Basic Initial Tests for All Patients

1. Comprehensive urinalysis:

   • RBC count per high-power field
   • RBC morphology (dysmorphic vs. eumorphic) using phase contrast microscopy if available
   • Presence of casts, crystals, WBCs
   • Protein measurement (dipstick and quantification if positive) 1

2. Urine culture to rule out infection 1, 5

3. Serum creatinine to assess renal function 1

4. Complete blood count with platelets to evaluate for anemia or coagulopathy 1

Additional Tests Based on Initial Findings

For Suspected Glomerular Disease:

• 24-hour urine protein or spot protein-to-creatinine ratio 1
• Blood urea nitrogen (BUN) 1
• Serum complement levels (C3, C4)
• Antinuclear antibody (ANA), anti-double-stranded DNA
• Hepatitis B and C serology
• ANCA testing if vasculitis suspected
• Audiogram and slit lamp examination if Alport syndrome suspected 1

For Suspected Non-Glomerular Disease:

• Urine calcium-to-creatinine ratio to assess for hypercalciuria 1, 5
• Urine cytology (especially in patients with risk factors for transitional cell carcinoma) 1
• Coagulation studies if bleeding disorder suspected

Imaging Studies Based on Clinical Presentation

For Persistent Unexplained Hematuria:

• Renal and bladder ultrasound as initial imaging 1, 5
• CT urography for patients at high risk for urothelial carcinoma 3
• Cystoscopy for patients with risk factors for bladder cancer 1

Special Considerations

When to Consider Renal Biopsy:

• Persistent glomerular hematuria with proteinuria
• Declining renal function
• Systemic disease with renal involvement 1, 6

When to Refer to Specialists:

• Nephrology: For glomerular disease, persistent unexplained hematuria >2 weeks, or need for renal biopsy 4
• Urology: For gross hematuria, suspected malignancy, or urolithiasis 1, 2

Common Pitfalls to Avoid

1. Failure to distinguish glomerular from non-glomerular hematuria - This distinction is crucial for directing further evaluation
2. Overlooking benign causes - Always rule out exercise, menstruation, or medication-related hematuria before extensive workup 1
3. Inadequate follow-up - Patients with isolated hematuria should be monitored for development of hypertension, proteinuria, or renal insufficiency 1
4. Missing malignancy - Gross hematuria carries significant risk of malignancy and requires prompt urologic evaluation 2

By following this systematic approach to the differential diagnosis and laboratory evaluation of hematuria, clinicians can efficiently identify the underlying cause and implement appropriate management strategies.