Hematuria

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Hematuria

Definition

Hematuria is the presence of blood in the urine. By convention:

Gross (macroscopic) hematuria — visible to the naked eye
Microscopic hematuria — detected only on urinalysis; defined as ≥3 RBCs/high-power field (HPF) on microscopic examination of a properly collected midstream clean-catch specimen

Urine dipstick alone is insufficient — it can be positive with myoglobinuria, hemoglobinuria, or oxidizing contaminants. Microscopic confirmation is required before initiating a full workup. — Campbell-Walsh-Wein Urology

Pseudohematuria (Red Urine Without RBCs)

Conditions that cause red/brown urine without true hematuria include:

Drugs: phenazopyridine, rifampin, nitrofurantoin, chloroquine, hydroxychloroquine
Foods: beets, blackberries, rhubarb
Metabolic: porphyria, myoglobinuria, hemoglobinuria, urate crystals
Dehydration (concentrated pigments)

Dipstick is positive in myoglobinuria/hemoglobinuria but microscopy shows no RBCs. — Rosen's Emergency Medicine

Classification by Origin

1. Glomerular Hematuria (Nephrologic)

Key features on urinalysis:

Dysmorphic RBCs — specifically acanthocytes (vesicle-like protrusions); >5% acanthocytes strongly suggests glomerular origin
Red cell casts (pathognomonic) or mixed RBC/WBC casts
Concurrent proteinuria strongly supports glomerular disease
This pattern constitutes nephritic urine

Nephritic syndrome = hematuria + impaired renal function + hypertension

Causes of glomerular hematuria:

Category	Examples
Genetic/structural	Alport syndrome (COL4A3/A4/A5 mutations), Thin Basement Membrane Nephropathy
IgA-mediated	IgA nephropathy (most common primary GN worldwide), IgA vasculitis (HSP)
Immune complex	MPGN, C3 glomerulopathy, post-infectious GN
Autoimmune	Lupus nephritis (SLE), ANCA vasculitis, anti-GBM disease (Goodpasture)
Vascular	Thrombotic microangiopathy (HUS/TTP), malignant hypertension

— Brenner & Rector's The Kidney

2. Non-Glomerular Hematuria (Urologic)

RBCs are eumorphic (normal shape); no casts. Bleeding from kidneys, ureters, bladder, prostate, or urethra.

Common urologic causes:

Urolithiasis (most common cause in adults overall)
Urinary tract infection / cystitis (most common cause in young women)
Bladder cancer — most common cause of gross hematuria in patients >50 years; found in 20–25% with gross hematuria
Renal cell carcinoma
Urothelial carcinoma (upper tract)
Benign prostatic hyperplasia (BPH — increased vascularity)
Renal papillary necrosis (sickle cell, analgesic nephropathy, diabetes)
Vascular: renal AV fistula, AAA (must exclude in ED)
Exercise-induced (transient, resolves with rest)
Trauma / urologic procedures
Anticoagulation (supratherapeutic — does not cause hematuria at therapeutic levels)
Hemorrhagic cystitis: cyclophosphamide, ifosfamide, radiation, BK virus (especially in immunocompromised/transplant patients), adenovirus

Localizing the Bleeding

Stream timing provides clues:

Pattern	Likely source
Initial stream hematuria	Urethra or prostate
Terminal hematuria	Bladder neck (contracts at end of voiding)
Total stream hematuria	Bladder or upper tract

Clot morphology:

Vermiform (worm-shaped) clots → formed in upper urinary tract (ureter molds them)
Cuboid/amorphous clots → formed in bladder

Risk Factors for Urologic Malignancy

Age >35 years (cystoscopy warranted)
Male sex
Smoking (most important modifiable risk factor for bladder cancer)
Industrial chemical exposure (aromatic amines, benzidine, dyes)
Prior alkylating chemotherapy (cyclophosphamide, ifosfamide)
Analgesic abuse (phenacetin)
Chronic foreign body / indwelling catheter (squamous cell carcinoma risk)
Schistosomiasis (squamous cell bladder cancer)
Gross hematuria (higher yield than microscopic)

Evaluation

Initial Assessment

Confirm true hematuria by microscopy (rule out pseudohematuria, menstruation, catheter artifact)
History: UTI symptoms? Trauma? Recent urologic procedure? Family history of renal disease? Medications? Smoking/occupational exposure?
Physical exam: BP, edema (nephrotic/nephritic), abdominal mass/bruit, flank tenderness, genital/rectal exam
Urinalysis with microscopy: RBC morphology, casts, proteinuria
Urine culture: to exclude infection
Renal function tests (serum creatinine, eGFR)

AUA Guidelines for Asymptomatic Microhematuria (AMH)

Step 1: Exclude benign causes (UTI, menstruation, recent procedure) → treat and repeat UA. If clears → release from care.

Step 2: If no benign cause → proceed with full evaluation:

Renal function testing
Cystoscopy — recommended for all adults ≥35 years old and/or those with malignancy risk factors; may be omitted in patients <35 without risk factors
CT Urogram (CTU) — preferred upper tract imaging (multiphasic CT with pre-contrast, nephrographic, and excretory phases); highest sensitivity/specificity for renal parenchymal and upper tract lesions
- Alternatives if CTU contraindicated (pregnancy, contrast allergy, renal insufficiency): MR urogram, retrograde pyelograms + non-contrast CT/US

If nephrologic signs (proteinuria, dysmorphic RBCs, red cell casts, AKI) → concurrent nephrology referral

Step 3 — Follow-up:

Negative evaluation: annual UA for ≥2 years
Persistent MH after negative evaluation: consider nephrology referral; repeat anatomic evaluation in 3–5 years or sooner if clinically indicated

Fig. AUA guideline algorithm for evaluation of asymptomatic microhematuria — Campbell-Walsh-Wein Urology

Symptomatic Microhematuria

Malignancy risk higher (~10.5% vs <5% asymptomatic)
Cystoscopy recommended regardless of age
Urine cytology is an option (but does not replace cystoscopy)

Gross Hematuria

Malignancy in 20–25%; cause found in ~50%
Assess hemodynamic stability, CBC (anemia), coagulation parameters if on anticoagulation
Full evaluation: cystoscopy + upper tract imaging (CTU) + urine cytology
If culture-documented UTI → treat first, then repeat UA to confirm clearance

Special Situations

Scenario	Key Point
Children	Microscopic hematuria defined as >5 RBCs/HPF on ≥2 weekly samples; most common cause is glomerular; evaluate for IgA nephropathy, Alport syndrome, hypercalciuria
Young women	Exclude UTI first — most common cause
Renal transplant recipients	Follow AUA AMH guidelines; additionally include BK virus in the differential (confirm with urine cytopathology and BK virus titers)
Anticoagulated patients	Therapeutic anticoagulation does NOT cause hematuria; persistent hematuria requires full workup
Post-exercise	Transient, benign; resolves within 24–72 hours with rest
Hemorrhagic cystitis	Cyclophosphamide/ifosfamide (acrolein metabolite) — prevented with mesna + hydration; treatment: irrigation, intravesical agents, embolization, or cystectomy in refractory cases

Urine Cytology and Tumor Markers

Routine cytology is NOT recommended for asymptomatic MH workup
High sensitivity for high-grade/CIS bladder cancer; low sensitivity for low-grade lesions
Blue-light cystoscopy (with ALA or HAL) — AUA recommends against use for MH evaluation (not validated in MH populations)
Urine NMP22, BTA, and other biomarkers: not recommended as standalone substitutes for cystoscopy

Key Statistics

Up to 25% of adults with hematuria are found to have a urologic malignancy
2.6% malignancy rate in screening studies of asymptomatic MH
~61% of hematuria patients have no significant pathology identified
Bladder cancer accounts for 97% of malignancies found in patients >35 with AMH
Gross hematuria: 30–40% have urinary tract malignancy (vs 5% in asymptomatic MH)

Sources: Campbell-Walsh-Wein Urology | Brenner & Rector's The Kidney | Rosen's Emergency Medicine | Textbook of Family Medicine 9e | National Kidney Foundation Primer on Kidney Diseases

Recent evidence: A 2023 systematic review and meta-analysis in J Urol (PMID 36883858) specifically evaluated diagnostic imaging modalities for asymptomatic microhematuria, supporting CTU as the preferred modality.

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