⚠️ Must-Not-Miss Diagnoses
Urothelial malignancy (bladder cancer — most common cause of gross hematuria in adults >35), renal cell carcinoma, upper tract urothelial carcinoma, rapidly progressive glomerulonephritis (RBC casts = emergency).
Differential Diagnosis by Key Features
| Clinical Feature | Think Of | Priority |
|---|---|---|
| Painless gross hematuria, smoker, >35 years old | Bladder cancer | HIGH — urgent urology referral |
| Flank pain + hematuria, colicky, radiating to groin | Nephrolithiasis | Moderate |
| Dysuria + frequency + hematuria, women | UTI/cystitis | Common, treat first |
| RBC casts on microscopy, proteinuria, hypertension | Glomerulonephritis | HIGH — nephrologist urgently |
| Recent strep infection + hematuria, child or young adult | Post-streptococcal GN | Moderate |
| Hematuria + flank mass + weight loss | Renal cell carcinoma | HIGH |
| BPH symptoms + hematuria, elderly man | BPH with hematuria | Moderate — still needs workup |
Systematic Approach
Confirm
True vs pseudo-hematuria
Confirm blood on dipstick is true hematuria. Myoglobinuria (rhabdomyolysis), hemoglobinuria (hemolysis), and certain foods/medications (beets, rifampin) cause red urine with negative urine microscopy for RBCs.
Microscopy
Urine microscopy is essential
RBC casts = glomerulonephritis (nephrology emergency). Dysmorphic RBCs = glomerular origin. Normal-appearing RBCs = lower urinary tract source. WBC casts = pyelonephritis. Cast-free = stone, tumor, or infection most likely.
Localize
Upper vs lower tract
Timing: initial stream (urethral/prostate), terminal (bladder neck/prostate), total (upper tract or bladder). Clots suggest significant bleeding — urology referral. Flank pain suggests upper tract.
Workup
Malignancy evaluation in appropriate patients
All adults >35 with gross hematuria and adults with risk factors and microscopic hematuria need: CT urography + cystoscopy (urology referral). Younger patients with microscopic hematuria and UTI symptoms: treat and recheck after treatment.
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