DEFINITION

Hematuria is defined as the abnormal presence of red blood cells (RBCs) in the urine and is commonly divided into gross and microscopic hematuria. Gross, or visible, hematuria can result from as little as 1 mL of blood in 1 L of urine, and therefore the color does not reflect the degree of blood loss. Also, numerous other substances can induce such a color change (see later, “Signs and Symptoms”). When true gross hematuria exists, the literature universally supports a full evaluation.¹

Microscopic hematuria is often found incidentally during office evaluation of urinary tract infection symptoms or during routine health screening. Approximately one million RBCs pass into the urine daily, which corresponds to 1 to 3 RBCs/high-power (HPF) field in centrifuged urine sediment examined microscopically.² Although much controversy exists, the American Urological Association (AUA) defines microscopic hematuria as 3 RBCs/high-power field on microscopic examination of the centrifuged urine specimen in two of three freshly voided, clean catch, midstream urine samples.³ Confirmation on repeat testing takes into account the intermittent nature of hematuria found in some diseases.

PREVALENCE

The reported prevalence of asymptomatic hematuria in adults varies widely. Population-based studies have shown prevalence rates of less than 1% to as high as 16%. This range is attributed to differences in patient demographics, amount of follow-up, definition and diagnostic technique, and the number of screening tests per patient.¹ Patients at high risk for urologic disease, such as older men, have a higher prevalence of hematuria.⁴

PATHOPHYSIOLOGY

The pathophysiology of hematuria depends on the anatomic site in the urinary tract from which blood loss occurs. A distinction has conventionally been drawn between glomerular and extraglomerular bleeding, separating nephrologic and urologic disease.

Blood originating from the nephron is termed glomerular or nephronal hematuria.⁵ RBCs can enter the urinary space from the glomerulus or, rarely, from the renal tubule. Disruption of the filtration barrier in the glomerulus may result from inherited or acquired abnormalities in the structure and integrity of the glomerular capillary wall. These RBCs can be trapped in Tamm-Horsfall mucoprotein and will be manifest in the urine by RBC casts. Finding casts in the urine represents significant disease at the glomerular level. However, in disease of the nephron, casts can be absent and isolated RBCs may be the only finding. The presence of proteinuria helps support a glomerular source of blood loss.

Hematuria without proteinuria or casts is termed isolated hematuria. Although a few glomerular diseases may produce isolated hematuria, this finding is more consistent with extraglomerular bleeding. Anything that disrupts the uroepithelium, such as irritation, inflammation, or invasion, can result in normal-appearing RBCs in the urine. Such insults may include malignancy, renal stones, trauma, infection, and medications. Also, nonglomerular renal causes of blood loss, such as tumors of the kidney, renal cysts, infarction, and arteriovenous malformations, can cause blood loss into the urinary space. Clues to the specific causes of hematuria are discussed in the next section.

SIGNS AND SYMPTOMS

The history, physical examination, and review of systems can provide important clues to the nature of the underlying disease, narrow the differential diagnosis, and separate glomerular from extraglomerular bleeding in the patient who presents with hematuria. One of the most important considerations is age, because childhood causes of hematuria may differ greatly from those in the adult. For example, hypercalciuria is a common cause of hematuria in children but is rare in adults.² In older adults, even transient hematuria carries an appreciable risk of cancer and should be strongly considered for further evaluation.¹

A family history of renal failure and cerebral aneurysms suggests polycystic kidney disease. Hearing loss and renal failure in male members of a family are seen in Alport’s disease. A family history without these symptoms may suggest thin basement membrane disease. A tendency to form kidney stones may run in families.

Many ingested substances can cause color change in the urine that can be mistaken for blood, and careful dietary and medication histories may elucidate a cause that can spare costly medical evaluations (Box 1).⁶ Recent strenuous exercise can produce transient hematuria by traumatic and nontraumatic mechanisms.⁷ Increased glomerular permeability may result from ischemic damage to the nephron as blood is shunted to exercising muscle or from an increased perfusion pressure secondary to efferent arteriolar vasoconstriction.

Constitutional symptoms such as fever, arthritis, and rash may suggest a glomerulonephritis associated with a connective tissue disease such as systemic lupus erythematosus. Hematuria or cola-colored urine following an upper respiratory illness is seen in immunoglobulin A (IgA) nephritis. Henoch-Schönlein purpura (HSP), the systemic variant of IgA nephritis, is commonly associated with palpable purpura of the skin and gastrointestinal manifestations. Absence of constitutional symptoms does not rule out a glomerulonephritis, however, because many primary renal diseases may manifest with only hematuria or proteinuria (or both).

A careful history of pain symptoms should be conducted. Suprapubic tenderness accompanied by dysuria, urgency, or hesitancy is found in cystitis. Prostatitis and urethritis also result in symptoms with urination. Severe pain in the flank, with radiation into the groin, is seen in ureteral distention or irritation by stones, clots, or other debris, such as that found in papillary necrosis. The rare loin pain–hematuria syndrome can have a similar pain pattern. Renal capsular distention from inflammation (pyelonephritis) or hematoma (trauma) can result in costovertebral angle tenderness. Bleeding or infection in a renal cyst can also result in costovertebral angle tenderness.

The characteristics of the hematuria can often help distinguish the cause and location of bleeding. A glomerular source of bleeding usually results in persistent microscopic hematuria, with or without periods of gross hematuria. In renal sources of hematuria, the blood is equally dispersed throughout the urine stream and does not clot.⁶ If clots are present, it is important to ascertain where in the urine stream they occur. Hematuria or clots at the beginning of the urine stream, initial hematuria, is a symptom of a urethral cause. Terminal hematuria, occurring at the end of the urine stream, may occur with a prostatic, bladder, or trigonal cause of hematuria.⁶

Important physical examination findings in the patient with hematuria may include fever and hypertension. The examination should include a search for signs of the above-mentioned systemic illnesses, such as rash and joint tenderness. Complete abdominal and back examinations should be performed to evaluate for tenderness or masses. In men, a complete genitourinary examination, including the prostate, is important to look for any visible urethral lesion or evidence of prostatitis. A pelvic examination should be done in women to exclude the possibility of contamination of urine by vaginal bleeding.