What is the differential diagnosis and management approach for a patient presenting with hematuria?

Differential Diagnosis of Hematuria

Classification and Major Categories

Hematuria has three primary source categories: urologic (non-glomerular), glomerular (renal parenchymal), and systemic causes, with the distinction between urologic and glomerular sources being the most critical initial determination. 1

Urologic (Non-Glomerular) Causes

Malignancy is the most concerning urologic cause and accounts for 30-40% of gross hematuria cases and 2.6-4% of microscopic hematuria cases 1, 2:

• Bladder cancer (transitional cell carcinoma) - most frequently diagnosed malignancy in hematuria workups 1
• Renal cell carcinoma 1
• Prostate cancer 1

Benign urologic conditions 1:

• Urinary tract infection - common cause of both microscopic and macroscopic hematuria 1
• Urolithiasis (kidney and ureteric stones) - causes painful hematuria 1
• Benign prostatic hyperplasia (BPH) - common in men, though does not exclude concurrent malignancy 1
• Trauma to kidneys or lower urinary tract 1

Glomerular (Renal Parenchymal) Causes

Glomerulonephritis 1:

• Post-infectious glomerulonephritis 1
• IgA nephropathy 1
• Lupus nephritis 1
• Vasculitis 1

Hereditary nephropathies 1:

• Alport Syndrome - hereditary nephritis with associated hearing loss 1
• Thin basement membrane nephropathy - autosomal dominant condition causing progressive chronic kidney disease 1

Other renal parenchymal disease 1:

• Interstitial renal disease, including drug-induced interstitial disease or analgesic nephropathy 1

Systemic and Other Causes

Hematologic disorders 1:

• Coagulopathies (hemophilia) 1
• Sickle cell disease - causes hematuria due to renal papillary necrosis 1

Metabolic causes 1:

• Hypercalciuria - can lead to nephrolithiasis 1
• Hyperuricosuria - can lead to nephrolithiasis 1

Vascular causes 1:

• Nutcracker syndrome - left renal vein compression causing hematuria with variable proteinuria 1

Transient/benign causes 1, 3:

• Vigorous exercise - causes transient hematuria 1
• Menstruation - causes contamination of urine samples in women leading to false-positive results 1
• Sexual activity 3
• Viral illness 3
• Recent urologic procedures 3

Critical Diagnostic Distinctions

Distinguishing Glomerular from Non-Glomerular Sources

Examine urinary sediment for dysmorphic RBCs and red cell casts 1, 3:

• >80% dysmorphic red blood cells suggests glomerular origin 1, 3
• >80% normal red blood cells suggests lower urinary tract bleeding 1
• Red cell casts are pathognomonic for glomerular disease 1, 3

Urine color provides diagnostic clues 1, 2:

• Tea-colored or cola-colored urine suggests glomerular source 1, 2
• Bright red urine suggests lower urinary tract bleeding 2

Proteinuria assessment 1, 3:

• Significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.2 g/g) strongly suggests renal parenchymal disease 1, 3
• The presence of both proteinuria and hematuria strongly suggests glomerular origin, particularly with dysmorphic RBCs or red cell casts 1

Age-Specific Differential Considerations

In children 1:

• Glomerulonephritis is a common cause 1
• Congenital anomalies 1
• Isolated microscopic hematuria without proteinuria or dysmorphic RBCs is unlikely to represent clinically significant renal disease 1

In adults, especially >35-40 years 1, 2:

• Malignancy becomes a significant risk factor 1
• Males ≥60 years are classified as high-risk and require complete urologic evaluation 1
• Males 40-59 years are intermediate-risk 1

Important Clinical Pearls

Never attribute hematuria solely to anticoagulation or antiplatelet therapy - these medications may unmask underlying pathology but do not cause hematuria themselves, and full evaluation must proceed regardless 1, 2, 3

Gross hematuria demands immediate action - it carries a 30-40% risk of malignancy and requires urgent urologic referral even if self-limited 1, 2, 3

Confirm microscopic hematuria properly - dipstick positivity (65-99% specificity) should be confirmed with microscopic analysis showing ≥3 RBCs per high-power field on at least two of three properly collected specimens before initiating extensive workup 1, 3

Medications like Cialis (tadalafil) do not cause hematuria - they may only unmask underlying urinary tract pathology that requires investigation 1