Hematuria

Hematuria, defined as the presence of red blood cells (RBCs) in the urine, can be classified according to quantity, occurrence during voiding, and origin of bleeding. In microhematuria, color changes in the urine are not clearly visible to the naked eye, and RBCs are only detectable under microscopy. Macrohematuria (gross hematuria) is visible discoloration of urine that results from frank blood. Glomerular hematuria originates from damage to the glomeruli. Nonglomerular hematuria results from damage to the kidneys or upper/lower urinary tract. If hematuria is detected, patients should undergo further evaluation (e.g., urinalysis) to determine the underlying cause. Other causes of red discoloration of the urine include myoglobinuria, porphyria, certain drugs (e.g., rifampin), and the consumption of certain foods (e.g., beetroots).

• Hematuria: the presence of red blood cells (RBCs) in the urine

According to quantity

• Macroscopic hematuria (gross hematuria)
  • Frank blood in urine resulting in visible red/brown discoloration of the urine
  • Suggests damage to the kidneys, upper/lower urinary tract (see “Nonglomerular hematuria” below)
• Microscopic hematuria ^[1]
  • RBCs are present in the urine sediment but no urine discoloration is visible to the naked eye.
  • Can indicate damage to the glomeruli (see “Glomerular hematuria” below)
  • However, a number of conditions can cause nonglomerular microscopic hematuria (e.g., UTIs, BPH, urolithiasis, malignancies, menstruation).

According to the occurrence during voiding

• Initial hematuria
  • Gross hematuria that occurs at the beginning of micturition and clears by the end of micturition
  • Typically suggests urethral damage (e.g., anterior urethral injury, posterior urethral injury)
• Terminal hematuria
  • Passage of blood or clots in urine during the last part of micturition (when the bladder neck contracts)
  • Suggests damage to the bladder neck, prostate, or trigonal area (e.g., benign prostatic hyperplasia, prostatitis)
• Total hematuria
  • Passage of blood or clots throughout the entire micturition
  • Suggests damage to the bladder, ureters or kidneys (e.g., urolithiasis, UTI, polycystic kidney disease)
• Painless hematuria (asymptomatic hematuria)
  • Passage of blood or clots in urine in the absence of renal or urinary symptoms
  • Suggests malignancy (e.g., transitional cell cancer, renal cell carcinoma, prostate cancer)

Gross painless hematuria is the most common clinical finding in urinary tract cancer and should be evaluated with cystoscopy.

According to origin

Glomerular hematuria

• Nephritic syndrome
  • Characteristic of glomerulonephritis
  • Hematuria with proteinuria is considered glomerulonephritis until proven otherwise.
• Isolated hematuria: the presence of RBCs in the urine with no other urinary abnormalities (e.g., changes in urine protein, serum creatinine, or blood pressure)
  • Transient isolated hematuria
    • Strenuous exercise (i.e., exercise-induced hematuria)
    • Infections
  • Persistent isolated hematuria
    • Most likely IgA nephropathy
    • Alport syndrome
    • Thin basement membrane nephropathy

Nonglomerular hematuria

• Urolithiasis
• Infection
  • Cystitis
  • Urethritis
  • Prostatitis
• Malignancy: especially if otherwise asymptomatic
  • Urothelial cancer
  • Renal cell carcinoma
  • Prostate cancer
  • In children, nephroblastoma
• Coagulation disorders
  • Platelet dysfunction
  • Hemophilia
• Urinary tract obstruction
  • Benign prostatic hyperplasia
  • Congenital anomalies
• Polycystic kidney disease
• Renal papillary necrosis
  • Sickle cell disease
  • Acute pyelonephritis
  • Diabetes mellitus
  • Analgesics
• Trauma (e.g., urethral, bladder, ureteral, or renal injury) ^[2]
• Drugs
  • Cyclophosphamide, sulfonamides
  • Warfarin, heparin

Medical history and physical examination

• Personal and family history
  • Kidney disease (e.g., polycystic kidney disease) or renal failure
  • Sickle cell disease
• Medication: e.g., anticoagulants, nephrotoxic agents
• Travel history: especially areas endemic for Schistosoma haematobium or tuberculosis
• Additional urinary symptoms
  • Dysuria (pain, burning, urge to void)
  • Flank pain
  • Difficulty voiding (urine retention, straining, intermittent stream, dribbling)
• Additional nonurinary symptoms
  • Recent or current upper respiratory infection
  • Skin changes (e.g., edema, rashes, petechiae, purpura)
  • Menstruational abnormalities

Urinalysis

• Urine dipstick: detects heme in urine (high sensitivity, low specificity)
  • A negative result for heme on urine dipstick makes hematuria very unlikely.
  • A positive result for heme does not confirm hematuria because the test does not distinguish between the presence of RBCs, hemoglobin, and myoglobin.
  • If additional proteinuria is present, evaluate for glomerular diseases.
• Urine sediment: Confirm hematuria with microscopy (≥ 3 RBCs/HPF).
  • If RBC casts and proteinuria are present: Evaluate for glomerular diseases.
  • If the morphology of RBCs is normal: Evaluate for nonglomerular causes (e.g., coagulation disorders, kidney stones, malignancy).
  • Urine that is positive for heme on dipstick but shows no RBCs on microscopy indicates hemoglobinuria or myoglobinuria.
  • In hemoglobinuria and myoglobinuria, the urine remains pigmented after centrifugation because the pigments are dissolved in the urine and do not settle at the bottom like RBCs in hematuria.
• Urine culture: Perform if clinical signs of infection exist or dipstick is positive for WBCs (pyuria) and/or leukocyte esterase (see “Urinary tract infection”).

When hematuria (red or brown urine, positive urine dipstick) is suspected, the presence of RBCs must be confirmed with microscopic analysis of the urine sediment.

Findings of glomerular and nonglomerular hematuria

Diagnosis of underlying disease

• See “Glomerulonephritis.”
• See “Urinary tract infection.”
• See “Urolithiasis.”
• See “Bladder cancer.”

• Hemoglobinuria and myoglobinuria
  • Both conditions cause red, amber, or “Coca-Cola” colored transparent urine that remains pigmented after centrifugation.
  • Urine remains pigmented after centrifugation because the pigments are dissolved in the urine and do not settle at the bottom like RBCs in hematuria.
• Porphyrias
  • Tea colored urine in porphyria cutanea tarda
  • Red-purple urine in acute intermittent porphyria
• Beeturia: red discoloration of urine after eating beetroot
• Drug-induced urine discoloration
  • Rifampin: harmless red-orange discoloration of bodily fluids (urine, sweat, tears)
  • Phenazopyridine: orange discoloration of urine

The differential diagnoses listed here are not exhaustive.