Hematuria is red blood cells (RBCs) in urine, specifically > 3 RBCs per high-power field on urine sediment examination. Urine may be red, bloody, or cola-colored (gross hematuria with oxidation of blood retained in the bladder) 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:
Hemoglobin or myoglobin in urine
Porphyria (most types)
Foods (eg, beets, rhubarb, sometimes food coloring)
Pathophysiology of Isolated Hematuria
Red blood cells (RBCs) may enter urine from anywhere along the urinary tract—from the kidneys, collecting system and ureters, prostate, bladder, and urethra. In females, normal or abnormal uterine bleeding may be misdiagnosed as hematuria.
Etiology of Isolated Hematuria
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 Some Specific Causes of Hematuria).
The most common specific causes differ somewhat by age, but overall the most common are
Urinary tract infections (UTIs)
Urinary calculi (in adults)
Congenital or acquired anatomic abnormalities
Cancers of the genitourinary system
Vigorous exercise may cause transient hematuria. 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 beta-hemolytic streptococcal infection), systemic rheumatic diseases (eg, systemic lupus erythematosus [SLE], granulomatosis with polyangiitis, immunoglobulin A–associated vasculitis [Henoch-Schönlein purpura] in children), and blood disorders (eg, mixed cryoglobulinemia, serum sickness). Worldwide, IgA nephropathy is the most common form of glomerulonephritis. Thin basement membrane disease and mild IgA nephropathy may cause isolated hematuria; however, most other glomerular causes of hematuria are accompanied by proteinuria.
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. Mycobacterium tuberculosis may also infect the lower or upper urinary tract and cause hematuria, occasionally causing urethral strictures.
Other causes of hematuria include
Urinary tract instrumentation or procedure (eg, Foley catheterization, prostate or kidney biopsy, lithotripsy)
Radiation cystitis
Drug-induced hemorrhagic cystitis
Vascular etiology—which is rare (eg, renal infarction, renal vein embolism, renal arteriovenous malformation)
Some Common Specific Causes of Hematuria
Cause | Suggestive Findings | Diagnostic Approach* |
|---|---|---|
Infection | Urinary irritative symptoms, with or without fever | Urinalysis and culture |
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 systemic rheumatic disease Usually proteinuria (except with thin basement membrane disease and mild IgA nephropathy) | Urinalysis Urine sediment examination for RBC cast and dysmorphic RBCs Serologic tests |
Mainly in patients > Sometimes voiding symptoms with bladder cancer Often systemic symptoms with renal cell carcinoma | In all patients without another obvious cause, cystoscopy and possible bladder biopsy; if prostate cancer is suspected, PSA and possibly prostate biopsy | |
Mainly in patients > 50 Often, urinary obstructive symptoms Palpably enlarged prostate | PSA Measurement of postvoid residual urine volume Ultrasonography of pelvis | |
Mainly in patients > 50 Often, urinary irritative and obstructive symptoms Painful, tender prostate with acute infection | Clinical evaluation Sometimes transrectal ultrasonography or cystoscopy | |
Chronic flank or abdominal pain Large kidneys | Ultrasonography or noncontrast CT/MRI of the abdomen | |
Renal papillary infarction or necrosis | Often in people with sickle cell disease or trait Sometimes heavy analgesic use (analgesic nephropathy) | Sometimes sickle cell preparation and Hb electrophoresis |
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 | Urinalysis and 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. | ||
Hb = hemoglobin; PSA = prostate-specific antigen; RBC = red blood cell. | ||
Evaluation of Isolated Hematuria
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 and whether they have vigorously exercised.
Review of systems should seek symptoms of possible causes, including joint pain and rashes (systemic rheumatic disease), and hearing loss or ocular manifestations (hereditary nephritis, also called Alport syndrome). Presence of fever, night sweats, or weight loss should also be noted.
Past medical history should include questions about any recent infections, particularly a sore throat that may indicate a group A beta-hemolytic streptococcal infection. Conditions known to cause urinary tract bleeding (particularly urinary tract calculi, sickle cell disease or trait, and glomerular disorders) should be sought, along with any history of congenital urinary tract anomalies. Also, conditions that predispose to a glomerular disorder, such as a systemic rheumatic disease (particularly systemic lupus erythematosus [SLE], granulomatosis with polyangiitis, microscopic polyangiitis ), endocarditis, shunt infections, and abdominal abscesses
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, and tuberculosis risk factors should be assessed. Medication history should note use of anticoagulants, antiplatelets (although controlled anticoagulation itself does not cause hematuria), and heavy analgesic use.
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 immunoglobulin A–associated vasculitis).
Red flags
The following findings are of particular concern:
Gross hematuria and concurrent proteinuria
Persistent microscopic hematuria, especially in older patients
Age > 50
Hypertension and edema
Systemic symptoms (eg, fever, night sweats, weight loss)
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 Some Common 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 beta-hemolytic streptococcal infection in children).
Calculi usually manifest with excruciating, colicky pain. Calculi may be present and not cause any discomfort. 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.
Systemic symptoms (eg, fever, night sweats, weight loss) may indicate cancer or subacute infection (eg, tuberculosis [TB]) or a systemic rheumatic disease.
On the other hand, some common findings (eg, prostate enlargement, excessive anticoagulation), 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 red blood cells (RBCs) suggests myoglobinuria or hemoglobinuria, porphyria, or ingestion of certain medications or foods. Generally, the presence of hematuria should be confirmed by testing a second specimen.
Presence of casts, protein, or dysmorphic RBCs (unusually shaped, with spicules, folding, and blebs) indicates a glomerular disorder. White blood cells 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 < 35 (including children) have only microscopic hematuria and no urine findings suggesting a glomerular disorder, no clinical manifestations suggesting a cause, no risk factors for cancer, and an identified benign cause (eg, infection, mild trauma), they can be observed, with urinalysis repeated every 6 to 12 months. If a benign cause is not evident or hematuria is persistent, testing is indicated (1), beginning with ultrasonography or CT with contrast, sometimes followed by cystoscopy.
Patients < 50 with gross hematuria or unexplained systemic symptoms require ultrasonography or CT of the abdomen and pelvis.
If urine or clinical findings suggest a glomerular disorder, renal function is evaluated by measuring blood urea nitrogen, 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 ≥ 35 require cystoscopy, as do patients who are < 35 but have risk factors, such as a family history of cancer, or systemic symptoms (1). Men ≥ 50 require discussion of testing for prostate-specific antigen through shared decision making; those with elevated levels require further evaluation for prostate cancer.
Evaluation reference
1. Barocas DA, Boorjian ST, Alvarez RD, et al: Microhematuria: AUA/SUFU guideline. J Urol 204(4):778-786, 2020. doi: 10.1097/JU.0000000000001297
Treatment of Isolated Hematuria
Treatment is directed at the cause.
Key Points
Red urine should be differentiated from true hematuria (red blood cells 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 for patients > 35 or for younger patients with systemic symptoms or risk factors for cancer.
