What is the differential diagnosis for microscopic hematuria?

Differential Diagnosis for Microscopic Hematuria

The differential diagnosis for microscopic hematuria encompasses urologic malignancies, benign urologic conditions, glomerular diseases, systemic disorders, and transient causes—with the critical distinction being between glomerular and non-glomerular sources guiding subsequent evaluation.

Urologic/Non-Glomerular Causes

Malignancies (Most Critical to Exclude)

• Bladder cancer (transitional cell carcinoma) is the most frequently diagnosed malignancy in hematuria cases, accounting for 30-40% of gross hematuria and 2.6-4% of microscopic hematuria cases 1
• Renal cell carcinoma presents with painless hematuria and requires cross-sectional imaging for detection 2
• Upper tract urothelial carcinoma (renal pelvis/ureter) frequently presents with painless hematuria and cannot be adequately assessed by ultrasound alone 2
• Prostate cancer should be considered in men with elevated PSA and hematuria 1

Benign Urologic Conditions

• Urinary tract infection is a common cause of both microscopic and macroscopic hematuria, with white blood cells and micro-organisms present in urine 3, 1
• Urolithiasis (kidney and ureteric stones) causes painful hematuria and is detected on CT urography 3, 1
• Benign prostatic hyperplasia is a common benign cause of hematuria in men, though it does not exclude concurrent malignancy 1
• Trauma to the kidneys or lower urinary tract, even minor trauma to an anomalous kidney, can cause significant hematuria 1

Glomerular/Renal Parenchymal Causes

Primary Glomerular Diseases

• IgA nephropathy (Berger disease) is the most common glomerular cause of isolated microscopic hematuria in adults 1, 2
• Post-infectious glomerulonephritis presents with low C3 complement levels and proliferative changes 1
• Thin basement membrane nephropathy is the most common autosomal dominant cause of benign familial hematuria 1, 2
• Alport syndrome is hereditary nephritis with associated hearing loss and ocular abnormalities, requiring audiogram and slit lamp examination if suspected 1

Secondary Glomerular Diseases

• Lupus nephritis presents with low complement levels (C3, C4), positive ANA, and anti-dsDNA antibodies 1
• ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis) causes rapidly progressive glomerulonephritis with positive PR3 or MPO antibodies 1
• Henoch-Schönlein purpura and other systemic vasculitides may present with isolated microscopic hematuria 1

Metabolic and Anatomic Causes

• Hypercalciuria and hyperuricosuria are metabolic abnormalities causing microscopic hematuria, sometimes with mild proteinuria, potentially leading to nephrolithiasis 1, 2
• Nutcracker syndrome (left renal vein compression) causes hematuria with variable proteinuria, diagnosed by ultrasound with Doppler 1, 2

Systemic and Hematologic Causes

• Coagulopathies such as hemophilia can cause hematuria due to bleeding disorders 1
• Sickle cell disease causes hematuria due to renal papillary necrosis 1
• Anticoagulants and antiplatelet agents may unmask underlying pathology but do not cause hematuria themselves—evaluation must proceed regardless 3, 1

Transient/Benign Causes

• Vigorous exercise can cause transient hematuria that resolves with cessation of activity 1
• Menstruation can cause contamination of urine samples in women, leading to false-positive results 1
• Recent sexual activity, viral illness, or minor trauma can cause self-limited hematuria 1

Key Diagnostic Distinctions

Differentiating Glomerular from Non-Glomerular Sources

• Glomerular bleeding is indicated by >80% dysmorphic red blood cells, red cell casts (pathognomonic), tea-colored or cola-colored urine, and significant proteinuria (>0.5 g/g protein-to-creatinine ratio) 3, 1
• Non-glomerular bleeding is indicated by >80% normal red blood cells, bright red urine, absence of significant proteinuria, and presence of clots 1

Common Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited, due to 30-40% malignancy risk that mandates urgent urologic referral 1
• Do not attribute hematuria to anticoagulation as the sole explanation—these medications may unmask underlying pathology but do not cause hematuria 3, 1
• Do not rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBCs/HPF before initiating workup 3, 1
• Infection does not exclude malignancy—persistent hematuria after UTI treatment requires full urologic evaluation 1, 4