What is the cause of hematuria in a patient with no kidney stones?

Causes of Hematuria Without Kidney Stones

When kidney stones are ruled out, the most important causes to consider are urinary tract infection, bladder or kidney cancer (especially in adults over 40), benign prostatic hyperplasia in men, and glomerular kidney diseases. 1

Primary Urologic Causes (Non-Stone)

Malignancy is the most critical diagnosis to exclude when stones are not present:

• Bladder cancer accounts for 30-40% of gross hematuria cases and 2.6-4% of microscopic hematuria cases 1
• Kidney cancer (renal cell carcinoma) must be considered, particularly in older adults 1
• Risk increases dramatically with age >35-40 years, smoking history, male gender, and occupational exposure to chemicals like benzenes or aromatic amines 1

Urinary tract infection is one of the most common benign causes:

• Look for accompanying symptoms: dysuria, urgency, frequency, fever 2
• White blood cells and micro-organisms in urine confirm infection 2
• Critical pitfall: Always obtain urine culture and repeat urinalysis 6 weeks after treatment to confirm hematuria resolution—persistent hematuria after treating infection requires full urologic evaluation 3

Benign prostatic hyperplasia (BPH) in men:

• Common benign cause in older males 1
• However, BPH does not exclude concurrent malignancy—gross hematuria from BPH must be proven through appropriate evaluation 1

Glomerular/Kidney Parenchymal Causes

Glomerulonephritis should be suspected when specific features are present:

• Tea-colored or cola-colored urine (not bright red) suggests glomerular bleeding 2, 1
• Proteinuria >2+ on dipstick, especially with protein-to-creatinine ratio >0.2 g/g 2, 1
• Dysmorphic red blood cells (>80%) or red blood cell casts on microscopy—these are pathognomonic for glomerular disease 2, 1
• Common types include post-infectious glomerulonephritis, IgA nephropathy (Berger disease), and lupus nephritis 2, 1

Alport syndrome (hereditary nephritis):

• Consider when there is family history of kidney disease and hearing loss 2, 1
• Requires audiogram and slit lamp examination if suspected 2

Thin basement membrane nephropathy:

• Autosomal dominant condition, most common cause of benign familial hematuria 2
• Screening family members' urine may be useful 2

Other Important Causes

Trauma (even minor):

• Any history of abdominal or flank trauma warrants consideration 2
• Minor trauma to an anomalous kidney can cause major clinical consequences 2

Medications and systemic conditions:

• Anticoagulants/antiplatelet agents do NOT cause hematuria—they may unmask underlying pathology that requires investigation 1, 3
• Coagulopathies (hemophilia) can cause hematuria due to bleeding disorders 1
• Sickle cell disease causes hematuria through renal papillary necrosis 1

Vigorous exercise can cause transient hematuria 1

Hypercalciuria and hyperuricosuria are metabolic causes that can lead to microscopic hematuria and potentially nephrolithiasis 1

Critical Diagnostic Approach

Distinguish glomerular from non-glomerular sources immediately:

• Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular) and red cell casts 1, 3
• Check for significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.2) 1, 3
• Measure serum creatinine to assess renal function 1, 3

For non-glomerular hematuria without benign explanation:

• Multiphasic CT urography is the preferred imaging to detect renal cell carcinoma, transitional cell carcinoma, and other upper tract pathology 1, 3
• Cystoscopy is mandatory for all adults with gross hematuria and most with microscopic hematuria who have risk factors 1, 3

For glomerular hematuria:

• Nephrology referral is indicated for persistent significant proteinuria, red cell casts, >80% dysmorphic RBCs, elevated creatinine, or hypertension with hematuria 1, 3
• Renal biopsy may be necessary for definitive diagnosis of IgA nephropathy, Alport syndrome, or other glomerular diseases 1

Common Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—it carries a 30-40% malignancy risk and requires urgent urologic referral 1, 4
• Do not attribute hematuria to anticoagulation therapy without full evaluation—these medications unmask pathology but don't cause hematuria 1, 3
• Confirm microscopic hematuria with ≥3 RBCs per high-power field on at least two of three properly collected specimens before initiating extensive workup 1, 3
• Factitious causes like food substances (beets) or medications coloring urine should be excluded—these don't have actual red blood cells in urine 2