Hematuria: A Merck Manual of Patient Symptoms podcast

Hematuria is RBCs in urine, specifically > 3 RBCs per high-power field on urine sediment examination. Urine may be red or bloody (gross hematuria) or not visibly discolored (microscopic hematuria). Isolated hematuria is urinary RBCs without other urine abnormalities (eg, proteinuria, casts).

Red urine is not always due to RBCs. Red or reddish brown discoloration may result from the following:

• Hb or myoglobin in urine
• Porphyria (most types)
• Foods (eg, beets, rhubarb, sometimes food coloring)
• Drugs (most commonly phenazopyridine, but sometimes cascara, diphenylhydantoin, methyldopa, phenacetin, phenindione, phenolphthalein, phenothiazine, and senna)

Pathophysiology

RBCs may enter urine from anywhere along the urinary tract—from the kidneys, collecting system and ureters, prostate, bladder, and urethra.

Etiology

Most cases involve transient microscopic hematuria that is self-limited and idiopathic. Transient microscopic hematuria is particularly common in children, present in up to 5% of their urine samples. There are numerous specific causes (see Table 2: Symptoms of Genitourinary Disorders: Some Common Specific Causes of Hematuria).

The most common specific causes differ somewhat by age, but overall the most common are

• UTI
• Prostatitis
• Urinary calculi (in adults)

Cancer and prostate disease are a concern mainly in patients > 50, although younger patients with risk factors may develop cancer.

Glomerular disorders can be a cause at all ages. Glomerular disorders may represent a primary renal disorder (acquired or hereditary) or be secondary to many causes, including infections (eg, group A β-hemolytic streptococcal infection), connective tissue disorders (eg, SLE at all ages, Henoch-Schönlein purpura [HSP] in children), and blood disorders (eg, mixed cryoglobulinemia, serum sickness). Worldwide, IgA nephropathy is the most common form of glomerulonephritis.

Schistosoma haematobium, a parasitic fluke that causes significant disease in Africa (and, to a lesser extent, in India and parts of the Middle East), can invade the urinary tract, causing hematuria. Schistosomiasis is considered only if people have spent time in endemic areas.

Table 2
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Some Common Specific Causes of Hematuria Cause Suggestive Findings Diagnostic Approach* Infection Urinary irritative symptoms, with or without fever Urinalysis and culture Calculi Sudden-onset, usually colicky, severe flank or abdominal pain, sometimes with vomiting Abdominal CT without contrast or ultrasonography of the abdomen Glomerular disease (numerous forms) In many patients, hypertension, edema, or both Possibly red or dark (cola-colored) urine Sometimes preceding infection, family history of renal disorders, or connective tissue disorder Urinalysis Urine sediment examination for RBC cast and dysmorphic RBCs Serologic tests Renal biopsy Cancer (bladder, kidney, prostate, ureter) Mainly in patients > 50 or with risk factors (smoking, family history, chemical exposures) Sometimes voiding symptoms with bladder cancer Often systemic symptoms with renal cell carcinoma In men, PSA, pelvic and prostate ultrasonography, biopsy In all patients, cystoscopy Prostatic hyperplasia Mainly in patients > 50 Often, urinary obstructive symptoms Palpably enlarged prostate PSA Measurement of postvoid residual urine volume Ultrasonography of pelvis Prostatitis Mainly in patients > 50 Often, urinary irritative and obstructive symptoms Painful, tender prostate Clinical evaluation Sometimes transrectal ultrasonography or cystoscopy Polycystic kidney disease Chronic flank or abdominal pain Hypertension Large kidneys Ultrasonography or noncontrast CT of the abdomen Sickle cell disease or trait In blacks, mainly children and young adults, often with known disease Sickle cell preparation Hb electrophoresis Endometriosis Hematuria coinciding with menses Clinical evaluation Trauma (blunt or penetrating) Usually, presentation as injury rather than as hematuria CT of the abdomen and pelvis Loin pain–hematuria syndrome Flank pain Hematuria CT Nutcracker syndrome Hematuria Left testicular pain Varicocele CT angiography *All patients require urinalysis and evaluation of renal function; older patients require imaging of kidneys and pelvis. PSA = prostate-specific antigen. Some Common Specific Causes of Hematuria Cause Suggestive Findings Diagnostic Approach* Infection Urinary irritative symptoms, with or without fever Urinalysis and culture Calculi Sudden-onset, usually colicky, severe flank or abdominal pain, sometimes with vomiting Abdominal CT without contrast or ultrasonography of the abdomen Glomerular disease (numerous forms) In many patients, hypertension, edema, or both Possibly red or dark (cola-colored) urine Sometimes preceding infection, family history of renal disorders, or connective tissue disorder Urinalysis Urine sediment examination for RBC cast and dysmorphic RBCs Serologic tests Renal biopsy Cancer (bladder, kidney, prostate, ureter) Mainly in patients > 50 or with risk factors (smoking, family history, chemical exposures) Sometimes voiding symptoms with bladder cancer Often systemic symptoms with renal cell carcinoma In men, PSA, pelvic and prostate ultrasonography, biopsy In all patients, cystoscopy Prostatic hyperplasia Mainly in patients > 50 Often, urinary obstructive symptoms Palpably enlarged prostate PSA Measurement of postvoid residual urine volume Ultrasonography of pelvis Prostatitis Mainly in patients > 50 Often, urinary irritative and obstructive symptoms Painful, tender prostate Clinical evaluation Sometimes transrectal ultrasonography or cystoscopy Polycystic kidney disease Chronic flank or abdominal pain Hypertension Large kidneys Ultrasonography or noncontrast CT of the abdomen Sickle cell disease or trait In blacks, mainly children and young adults, often with known disease Sickle cell preparation Hb electrophoresis Endometriosis Hematuria coinciding with menses Clinical evaluation Trauma (blunt or penetrating) Usually, presentation as injury rather than as hematuria CT of the abdomen and pelvis Loin pain–hematuria syndrome Flank pain Hematuria CT Nutcracker syndrome Hematuria Left testicular pain Varicocele CT angiography *All patients require urinalysis and evaluation of renal function; older patients require imaging of kidneys and pelvis. PSA = prostate-specific antigen.

Evaluation

History

History of present illness includes duration of hematuria and any previous episodes. Urinary obstructive symptoms (eg, incomplete emptying, nocturia, difficulty starting or stopping) and irritative symptoms (eg, irritation, urgency, frequency, dysuria) should be noted. Patients should be asked about the presence of pain and its location and severity.

Review of systems should seek symptoms of possible causes, including joint pain and rashes (connective tissue disorder).

Past medical history should include questions about any recent infections, particularly a sore throat that may indicate a group A ß-hemolytic streptococcal infection. Conditions known to cause urinary tract bleeding (particularly kidney calculi, sickle cell disease or trait, and glomerular disorders) should be sought. Also, conditions that predispose to a glomerular disorder, such as a connective tissue disorder (particularly SLE and RA), endocarditis, shunt infections, and abdominal abscesses, should be identified. Risk factors for GU cancer should be identified, including smoking (the most significant), drugs (eg, cyclophosphamide, phenacetin), and exposure to industrial chemicals (eg, nitrates, nitrilotriacetate, nitrites, trichloroethylene).

Family history should identify relatives with known polycystic kidney disease, a glomerular disorder, or GU cancer. Patients should be asked about travel to areas where schistosomiasis is endemic. Drug history should note use of anticoagulants or antiplatelet drugs (although anticoagulation itself does not cause hematuria).

Physical examination

Vital signs should be reviewed for fever and hypertension.

The heart should be auscultated for murmurs (suggesting endocarditis).

The abdomen should be palpated for masses; flanks should be percussed for tenderness over the kidneys. In men, a digital rectal examination should be done to check for prostate enlargement, nodules, and tenderness.

The face and extremities should be inspected for edema (suggesting a glomerular disorder), and the skin should be inspected for rashes (suggesting vasculitis, SLE, or HSP).

Red flags

The following findings are of particular concern:

• Gross hematuria
• Persistent microscopic hematuria, especially in older patients
• Age > 50
• Hypertension and edema

Interpretation of findings

Clinical manifestations of the various causes overlap significantly, so urine and often blood tests are required. Depending on results, imaging tests may then be needed. However, some clinical findings provide helpful clues (see Table 2: Symptoms of Genitourinary Disorders: Some Common Specific Causes of Hematuria).

• Blood clots in urine essentially rule out a glomerular disorder. Glomerular disorders are often accompanied by edema, hypertension, or both; symptoms may be preceded by an infection (particularly a group A β-hemolytic streptococcal infection in children).
• Calculi usually manifest with excruciating, colicky pain. Less severe, more continuous pain is more likely to result from infection, cancer, polycystic kidney disease, glomerulonephritis, and loin pain–hematuria syndrome.
• Urinary irritative symptoms suggest bladder or prostate infection but may accompany certain cancers (mainly bladder and prostate).
• Urinary obstructive symptoms usually suggest prostate disease.
• An abdominal mass suggests polycystic kidney disease or renal cell carcinoma.
• A family history of nephritis, sickle cell disease or trait, or polycystic kidney disease suggests that as a cause.
• Travel to Africa, the Middle East, or India suggests the possibility of schistosomiasis.

On the other hand, some common findings (eg, prostate enlargement, anticoagulant use), although potential causes of hematuria, should not be assumed to be the cause without further evaluation.

Testing

Before testing proceeds, true hematuria should be distinguished from red urine by urinalysis. In women with vaginal bleeding, the specimen should be obtained by straight catheterization to avoid contamination by a nonurinary source of blood. Red urine without RBCs suggests myoglobinuria or hemoglobinuria, porphyria, or ingestion of certain drugs or foods.

Presence of casts, protein, or dysmorphic RBCs (unusually shaped, with spicules, folding, and blebs) indicates a glomerular disorder. WBCs or bacteria suggest an infectious etiology. However, because urinalysis shows predominantly RBCs in some patients with cystitis, urine culture is usually done. A positive culture result warrants treatment with antibiotics. If hematuria resolves after treatment and no other symptoms are present, no further evaluation is required for patients < 50, especially women.

If patients < 50 (including children) have only microscopic hematuria and no urine findings suggesting a glomerular disorder, no clinical manifestations suggesting a cause, and no risk factors for cancer, they can be observed, with urinalysis repeated every 6 to 12 mo. If hematuria is persistent, ultrasonography or CT with contrast is suggested.

Patients < 50 with gross hematuria require ultrasonography or CT of the abdomen and pelvis.

If urine or clinical findings suggest a glomerular disorder, renal function is evaluated by measuring BUN, serum creatinine, and electrolytes; doing a urinalysis; and periodically determining the urine protein/creatinine ratio. Further evaluation of a glomerular disorder may require serologic tests, kidney biopsy, or both.

All patients ≥ 50 yr require cystoscopy, as do patients who are < 50 but have risk factors, such as a family history of cancer. Men ≥ 50 require testing for prostate-specific antigen; those with elevated levels require further evaluation for prostate cancer.

Treatment

Treatment is directed at the cause.

Key Points

• Red urine should be differentiated from hematuria (RBCs in urine).
• Urinalysis and urine sediment examination help differentiate glomerular from nonglomerular causes.
• Risk of serious disease increases with aging and with duration and degree of hematuria.
• Cystoscopy and imaging tests are usually needed only for patients > 50 or for younger patients with risk factors for cancer.

Last full review/revision September 2009 by Seyed-Ali Sadjadi, MD