Hematuria

Hematuria is the presence of ≥ 3 red blood cells (RBCs) per high-power field (HPF) in the urine. It is often classified by visibility and origin. In microscopic hematuria, urine appears normal to the naked eye, and RBCs are only detectable under microscopy. Macroscopic hematuria (gross hematuria) is visible discoloration of urine that results from frank blood. Glomerular hematuria originates from glomerular damage. Causes include glomerulonephritis (GN), e.g., IgA nephropathy or thin basement membrane disease. It is characterized by dysmorphic red blood cells observed on urine microscopy. Nonglomerular hematuria results from urothelial damage (e.g., nephrolithiasis, malignancy, cystitis, trauma), or tubulointerstitial disease (e.g., renal papillary necrosis, interstitial nephritis) and is characterized by normal RBC morphology on urine microscopy. The underlying cause is determined through further evaluation, e.g., urinalysis (UA) and imaging, and guides the appropriate management. Mimics of hematuria include myoglobinuria, porphyria, and the consumption of certain medications (e.g., rifampin) and foods (e.g., beetroots).

Hematuria is the presence of ≥ 3 RBCs per HPF in the urine and may be further categorized according to: ^[1]

• Visibility
  • Macroscopic hematuria; (gross hematuria): frank blood in urine resulting in visible bright red or red-brown discoloration of the urine
  • Microscopic hematuria: RBCs are present in the urine sediment, but no urine discoloration is visible to the naked eye. ^[2]
• Timing during urination
  • Initial hematuria: frank blood in the urine that occurs at the beginning of micturition and clears by the end of micturition
  • Terminal hematuria: passage of blood or clots in urine during the last part of micturition (when the bladder neck contracts)
  • Total hematuria: passage of blood or clots throughout micturition
• Associated features
  • Painless hematuria: passage of blood or clots in urine in the absence of renal or urinary symptoms
  • Isolated hematuria
    • The presence of RBCs in the urine with no other abnormalities (e.g., changes in urine protein, serum creatinine, or blood pressure)
    • Can be transient (e.g., exercise-induced hematuria, infection) or persistent
• Location of damage
  • Glomerular hematuria
  • Nonglomerular hematuria

Macroscopic hematuria in adults is most commonly caused by nephrolithiasis, UTI/pyelonephritis, BPH, or malignancy. ^[3]

Infectious ^[1][4][5]

• Urinary tract infection
• Urethritis
• Prostatitis
• Pyelonephritis
• Tuberculosis
• Schistosomiasis

Glomerular (glomerulonephritis) ^[1][4][5]

• Anti-GBM disease
• Immune complex-mediated GN
  • IgA nephropathy
  • IgA vasculitis
  • Postinfectious GN
  • Endocarditis
  • Cryoglobulinemic vasculitis
  • Systemic lupus erythematosus
• ANCA-associated GN
  • Eosinophilic granulomatosis with polyangiitis
  • Microscopic polyangiitis
  • Granulomatosis with polyangiitis
• Inherited glomerular disorders
  • Alport syndrome
  • Thin basement membrane disease

Tubulointerstitial ^[1][4][5]

• Acute interstitial nephritis
• Chronic interstitial nephritis
• Renal papillary necrosis from, e.g.:
  • Sickle cell disease
  • Acute pyelonephritis
  • Diabetes mellitus
  • Analgesics
• Crystalline nephropathy

Urothelial ^[1][4][5]

• Renal cell carcinoma
• Nephroblastoma (children)
• Nephrolithiasis
• Urethral strictures
• Urinary tract cancer
• Prostate cancer
• Benign prostatic hypertrophy
• Urinary tract polyps

Genitourinary trauma

• Renal injuries (e.g., blunt abdominopelvic trauma or penetrating thoracoabdominal trauma)
• Ureteral injuries (e.g., MVC deceleration injuries, posterior torso trauma, pelvic fracture)
• Urethral injuries (e.g., direct penile trauma, straddle injury)
• Bladder injuries (e.g., bladder rupture, penetrating pelvic trauma or blunt abdominopelvic trauma)
• Urinary tract instrumentation
  • Recent bladder catheterization
  • Recent urologic surgery (e.g., TURP, TURBT, percutaneous nephrostomy)
  • Invasive diagnostic investigations and procedures in urology

Structural ^[1][4][5]

• Polycystic kidney disease
• Medullary sponge kidney
• Vascular, e.g.:
  • AVM
  • Renal artery aneurysm
  • Renal vein thrombosis
  • Renal infarction
  • Left renal vein compression

Hematologic ^[1][4][5]

• Coagulopathy, e.g.:
  • Hemophilia
  • Platelet dysfunction
• Thrombotic microangiopathy (e.g., thrombotic thrombocytopenic purpura)

Inflammatory ^[1][4][5]

• Radiation-induced hemorrhagic cystitis
• Interstitial cystitis
• Renal transplant rejection

Medication-induced ^[1][4][5]

• Analgesics
• Aminoglycosides
• Calcineurin inhibitors
• Cyclophosphamide, ifosfamide (medication-induced hemorrhagic cystitis)

Approach ^[6][7][8]

• Macroscopic hematuria ^[6]
  • ABCDE approach
  • Initial management of genitourinary trauma if indicated
  • Suprapubic palpation to assess for bladder distention
  • Laboratory studies: CBC, coagulation studies
  • Assessment for postvoid residual volume
  • Urology consultation as needed for management (e.g., bladder irrigation to prevent clot retention) ^[6]
• Microscopic hematuria with proteinuria (e.g., nephritic sediment) ^[7][8]
  • Evaluate for causes of GN in consultation with nephrology.
  • Evaluate for red flags for RPGN (e.g., rapidly rising creatinine levels, hemoptysis).
  • See also “Management of nephritic syndrome.”

Hemorrhagic shock due to hematuria is rare but may occur in patients with prior radiation or vascular causes. If present, obtain type and screen and do not delay hemodynamic resuscitation and blood transfusion for diagnostic studies. ^[9]

Bladder irrigation to prevent clot retention ^[6][10][11]

Bladder irrigation may also be indicated for cystolithiasis and intravesical medication administration.

• Indication: macroscopic hematuria at risk of clot formation
• Goal: prevention of urine retention, pain, significant hemorrhage, and/or bladder distention or rupture
• Technique
  1. Insert urinary catheter: use large-bore (≥ 22 French) three-way Foley catheter
  2. Begin manual bladder irrigation.
  3. Initiate continuous bladder irrigation (CBI) after manual bladder irrigation.
  4. If macroscopic hematuria persists after initial CBI, obtain abdominal and pelvic imaging.
     • No residual clot: Continue CBI with normal saline as directed by urology.
     • Residual clot: Consider cystoscopy for clot evacuation, direct visualization, and management of bleeding source.

Manual bladder irrigation

1. Attach a 50–60 mL catheter-tipped syringe to the outflow port of the three-way Foley catheter.
2. Aspirate as much urine as possible to reduce discomfort.
3. Forcefully inject ∼ 50 mL of normal saline through the same port to break up clots.
4. Aspirate and discard the fluid, noting the return volume.
5. Repeat the irrigation process until urine is clear, then flush with an additional 1000 mL of saline.
6. Stop immediately if the return volume is significantly less than injected and consult urology.

Continuous bladder irrigation

1. Consult urology to determine irrigation duration.
2. Suspend two 2–4 liter bags of normal saline on an IV pole and connect to irrigation tubing.
3. Attach tubing to the inflow port of the three-way Foley catheter and the outflow port to a large drainage bag.
4. Start continuous gravity flow; adjust to keep urine light pink to clear (typically 1–2 L/hour).
5. Monitor outflow every 15–30 minutes.
6. Stop infusion if inflow significantly exceeds outflow.

CBI does not break up existing clots, always perform manual bladder irrigation before starting CBI.

Complications

• Infection
• Bladder distention and rupture
• Bladder spasms and pain
• Dilutional hyponatremia and/or other electrolyte abnormalities

History ^[12]

• Urinary symptoms
  • Timing of blood in urine
    • Initial hematuria: suggests urethral damage (e.g., urethritis, urethral stricture, urethral laceration)
    • Terminal hematuria: suggests damage to the bladder neck, prostate, or trigonal area (e.g., benign prostatic hyperplasia, prostatitis, bladder polyps)
    • Total hematuria: suggests damage to the bladder, ureters or kidneys (e.g., urolithiasis, UTI, polycystic kidney disease)
  • Blood clots in urine: characteristic of nonglomerular bleeding ^[3]
  • Lower urinary tract symptoms, e.g.:
    • Dysuria (pain, burning, urge to void): suggests infection
    • Difficulty voiding (urine retention, straining, intermittent stream, dribbling): suggests obstruction
  • Flank pain: characteristic of ureteral obstruction (e.g., urolithiasis, blood clot)
  • Suprapubic pain: often occurs in infections, urinary retention, bladder mass
• Nonurinary symptoms
  • Fever
  • Constitutional symptoms
  • Skin changes (e.g., edema, rashes, petechiae, purpura): suggests a systemic process (e.g., vasculitis)
  • Menstrual symptoms
  • Recent or current upper respiratory tract infection
• Past medical history
  • Chronic kidney disease, polycystic kidney disease
  • Sickle cell disease
  • Abnormal uterine bleeding, endometriosis
  • Recent surgery or instrumentation on or near the urinary tract
  • Chemotherapy (e.g., cyclophosphamide, ifosfamide)
  • Pelvic radiation
  • Autoimmune diseases (e.g., vasculitides)
• Medication: e.g., nephrotoxic agents, anticoagulants
• Family history: kidney disease
• Social history
  • Sexual history
  • Smoking history (including pack-years)
  • Recent strenuous exercise
  • Occupational exposures
• Travel history: especially areas endemic for schistosomiasis or tuberculosis

Painless hematuria is a typical finding in malignancy.

Focused physical examination ^[3][12]

• Abdomen and back examination to assess for CVA tenderness, renal mass, suprapubic tenderness, palpable bladder
• Pelvic examination to assess for other sources of blood (e.g., menstrual bleeding)
• DRE to assess for prostatitis, prostate mass
• Dermatological examination to assess for rash, petechiae, purpura
• Extremity examination to assess for arthritis, synovitis, peripheral edema
• See also “Clinical features of genitourinary trauma.”

Approach to hematuria ^[13][14][15]

• Identify and manage transient causes (e.g., UTI, nephrolithiasis); reassess for hematuria following treatment.
• Evaluate persistent hematuria based on suspected mechanism (e.g., glomerular vs. nonglomerular hematuria), regardless of whether the patient is receiving antiplatelet or anticoagulant therapy. ^[16]
• Obtain trauma diagnostics if there are general indications for imaging in genitourinary trauma.

Repeat the UA before pursuing further diagnostic evaluation if a benign etiology is suspected. Vigorous exercise, instrumentation to the urinary tract, sexual intercourse, menstruation, and fever are common causes of transient hematuria. ^[4]

Initial studies ^[12][15][16]

• BMP: to evaluate renal function
• Urine dipstick: to detect heme in urine (high sensitivity, low specificity)
• Urine microscopy: to confirm ≥ 3 RBCs per HPF and assess for WBCs, bacteria, nitrites, RBC morphology, and protein
  • Glomerular hematuria; : nephritic sediment (e.g., RBC casts, proteinuria, dysmorphic RBCs)
  • Nonglomerular hematuria: normal RBC morphology, otherwise bland urine sediment
  • No RBCs: mimics of hematuria (e.g., hemoglobinuria, myoglobinuria)
  • Crystals: suggestive of nephrolithiasis
  • WBCs, bacteria, nitrites, leukocyte esterase ^[1]
    • Consider infection as the cause in patients with (e.g., lower urinary tract symptoms).
    • Sterile pyuria: Causes include TB, analgesic nephropathy, and other tubulointerstitial diseases.
• Urine culture: to assess for complicated UTI (see “Urinary tract infections”)
• Urine microscopy with < 3 RBCs per HPF: Repeat UA three times at 6-week intervals. ^[13]

Glomerular and nonglomerular hematuria ^[1][12]

Dysmorphic RBCs, RBC casts, and/or significant proteinuria on urine microscopy suggest a glomerulopathy. ^[12]

Additional studies ^[15][16]

Nonglomerular hematuria

• Gross hematuria: Consult urology regarding CT urography followed by cystoscopy (with biopsy if needed) for diagnostic confirmation of urinary tract cancer. ^[15][16]
• Microhematuria: Order additional studies (e.g., imaging) for urinary tract cancer using risk-based assessment of microhematuria.

Glomerular hematuria

• Evaluate for causes of GN (e.g., anti-GBM disease, ANCA-associated GN) in consultation with nephrology.
  • Renal biopsy is usually required for diagnostic confirmation.
  • See “Management of nephritic syndrome” for diagnostic studies in patients with nephritic sediment.
• Consider imaging for urinary tract cancer using risk-based assessment of microhematuria.

Diagnosis of glomerular disease does not rule out urinary tract malignancy. ^[15]

Older age, male sex, and smoking are the main risk factors for urinary tract cancer. ^[15]

General principles ^[3][12]

• Definitive management is based on the underlying cause of hematuria.
• Provide supportive care measures to ensure:
  • Adequate urinary drainage (see “Bladder drainage for clot retention”).
  • Adequate hydration (e.g., via oral or IV fluids)

Repeat UA after treatment of transient causes of hematuria to confirm the resolution of hematuria.

Disposition ^[3]

• Inpatient management indications
  • Need for continuous monitoring and therapy
    • Ongoing massive hematuria (e.g., in hemorrhagic cystitis)
    • Sepsis (e.g., in complicated pyelonephritis)
    • Significant AKI (e.g., in RPGN or acute renal papillary necrosis)
  • Need for interventional therapy (e.g., procedures, IV therapy)
    • Complicated nephrolithiasis
    • Clot retention
    • Refractory pain
• Outpatient management: Consider for patients without need for urgent intervention or monitoring.

Referrals and follow-up

• Urology
  • Suspected or confirmed malignancy
  • Urinary tract obstruction, clot retention, or complicated nephrolithiasis
  • Known or suspected genitourinary trauma
  • Postoperative patient with hematuria (e.g., after cesarean birth, laparoscopic surgery)
• Nephrology
  • Suspected or confirmed glomerular disease
  • AKI at high risk of complications, e.g., AKI stage 3, indications for acute dialysis
• Primary care: uncomplicated disease, e.g., lower UTI, uncomplicated nephrolithiasis, or microscopic hematuria of unknown cause

• Heme-positive urine dipstick: remains pigmented after centrifugation ^[12]
  • Hemoglobinuria: pink or red urine
  • Myoglobinuria: rusty or cola-colored urine
  • False positives: alkaline urine; presence of semen, bacterial peroxidase, or oxidizing cleaning agents
• Heme-negative urine dipstick ^[12]
  • Porphyrias
    • Porphyria cutanea tarda: tea-colored urine
    • Acute intermittent porphyria: red-purple urine
  • Bile pigmenturia: brown urine
  • Food-induced urine discoloration
    • Beetroot
    • Rhubarb
  • Drug-induced urine discoloration ^[1]
    • Red-orange
      • Rifampin: discoloration of bodily fluids (urine, sweat, tears)
      • Phenazopyridine
      • Phenytoin
      • Deferoxamine
    • Dark brown or red-brown
      • Metronidazole
      • Levodopa
      • Methyldopa
      • Imipenem-cilastatin
      • Nitrofurantoin
      • Chloroquine
  • False negative: high vitamin C intake

Very high urine ascorbic acid levels can cause false-negative urine dipstick reactions for blood. ^[12]