Hematuria: Causes, Evaluation, and When to Investigate

Hematuria (blood in urine) is classified as gross (visible) or microscopic (≥3 RBC/HPF on microscopy). It is a symptom, not a diagnosis, and warrants systematic evaluation.

Differential Diagnosis by Anatomic Site

Category	Conditions	Key Features
Glomerular (Nephrologic)	IgA nephropathy, post-strep GN, lupus nephritis, ANCA vasculitis, thin basement membrane disease, Alport syndrome	Dysmorphic RBCs, RBC casts, proteinuria, hypertension, renal dysfunction
Non-Glomerular (Urologic)
Upper tract	Stones, urothelial carcinoma, papillary necrosis, TB, cysts (ADPKD), UPJ obstruction	Flank pain (colic), risk factors (smoking, analgesics)
Bladder	Cancer, cystitis, stones, schistosomiasis, radiation cystitis	Irritative voiding symptoms, smoking history
Prostate/Urethra	BPH, prostatitis, urethritis, urethral stricture, cancer	Male >50; obstructive symptoms
Systemic / Other	Anticoagulants, antiplatelets, bleeding disorders, sickle cell trait, exercise-induced, menstrual contamination, factitious	Medication review, coagulation studies, centrifuge urine to confirm RBCs

Diagnostic Algorithm

1. Confirm true hematuria: Microscopy (dipstick false + from myoglobin, hemoglobin, oxidizing agents, semen).
2. History/Physical: Pain, trauma, medications, family history, risk factors.
3. Urinalysis + Culture: RBC morphology, protein, WBC, casts, bacteria.
4. Risk stratification: Low (age <35, non-smoker, <25 RBC/HPF, no risk factors) → repeat UA in 6 mo. High → imaging + cystoscopy.
5. Imaging: CT urogram (gold standard for urothelial cancer, stones); US (radiation-averse, pregnant); MRI (contrast allergy, renal impairment).
6. Cystoscopy: Direct bladder/urethra visualization; office-based, flexible.
7. Nephrology referral: If glomerular features (proteinuria, casts, HTN, renal insufficiency).

Special Considerations

• Exercise-induced: Benign, resolves 24–72 hrs; exclude other causes if persistent.
• Pediatric: Hypercalciuria, UPJ obstruction, nutcracker syndrome, thin basement membrane.
• Anticoagulated patients: Still require evaluation; warfarin does not cause hematuria without underlying lesion.

Red Flags for Urgent Urology/Nephrology Referral

• Gross hematuria + clots
• Acute kidney injury
• Uncontrolled hypertension
• Suspected renal mass on imaging
• Persistent microscopic hematuria >6 months (high-risk)