Evaluation of hematuria in adults

INTRODUCTION — 

Hematuria is defined as the presence of blood in the urine. It can be visible to the naked eye (gross [visible] hematuria) or detectable only on examination of the urine sediment by microscopy or automated microscopy (microscopic hematuria).

Hematuria that is not explained by an obvious condition (eg, cystitis, ureteral stone) is fairly common. In many such patients, particularly young adult patients, the hematuria is transient and of no consequence. On the other hand, there is an appreciable risk of malignancy in older patients (eg, over age 35 years) with hematuria, even if transient. However, even among older patients, a urologic cause for the hematuria can often not be identified.

The evaluation of hematuria in adults will be reviewed here. Other aspects of hematuria are discussed separately:

●Evaluation of hematuria in children - (See "Evaluation of gross hematuria in children" and "Evaluation of microscopic hematuria in children".)

●Isolated persistent glomerular hematuria - (See "Isolated and persistent glomerular hematuria in adults".)

●Management of acute gross hematuria - (See "Management of acute gross hematuria in adults".)

●Exercise-induced hematuria - (See "Exercise-induced hematuria".)

DEFINITIONS — 

Hematuria is defined as the presence of blood in the urine. It can be categorized as follows:

●Gross (visible) hematuria – Gross (visible) or macroscopic hematuria refers to blood in the urine that is visible to the naked eye. It can present with red, pink, “rusty”, or brown urine. The color change does not necessarily reflect the degree of blood loss, since as little as 1 mL of blood per liter of urine can induce a visible color change.

●Microscopic hematuria – Microscopic hematuria refers to blood that is detectable only on examination of the urine sediment by microscopy (picture 1) or automated microscopy. It may be discovered incidentally when blood (either red blood cells [RBCs] or hemoglobin) is found on a urinalysis or dipstick done for other purposes.

Microscopic hematuria is commonly defined as the presence of ≥3 RBCs per high-power field (40x magnification) in a centrifuged fresh urine sediment [1]. However, there is no “safe” lower limit below which significant disease can be excluded [2]. Lowering the cut-off value of RBCs chosen to define hematuria results in a greater number of false positive test results (ie, no underlying abnormality is found). On the other hand, if higher cut-off values are chosen, it is more likely that the test will miss the presence of significant abnormalities.

GENERAL PRINCIPLES

Detection of hematuria — There are two methods of detecting hematuria:

●Urine dipstick – The urine dipstick test for blood (heme) is a highly sensitive test for the detection of hematuria. Heme acts as a pseudoperoxidase, and when heme-containing urine is exposed to peroxide and a chromogen on the test strip, a color change takes place. However, a positive dipstick for heme may result not only from urinary red blood cells (RBCs) but also from free hemoglobin or free myoglobin. Thus, a positive dipstick must always be confirmed with microscopic examination of the urine.

A positive dipstick test of 1+ or greater is considered to be significant hematuria. A trace positive result, unless accompanied by RBCs on urine microscopy, is not considered evidence of hematuria.

False positive dipstick tests can be caused by the presence of semen in the urine, an alkaline urine with a pH >9, or contamination with oxidizing agents used to clean the perineum. Rarely, a very dilute urine produces osmotic lysis of almost all of the urinary RBCs, resulting in an apparently false positive test (because the dipstick detects hemoglobin but no RBCs are visible). This does not constitute a false positive test.

False negative dipstick tests are unusual; as a result, a negative dipstick test usually excludes abnormal hematuria. False negative dipstick tests have been reported in patients ingesting large amounts of vitamin C; the clinical relevance of this observation is not known [3].

●Microscopic examination – A positive dipstick for hematuria should be confirmed by microscopic examination of the sediment of 10 to 15 mL of centrifuged fresh urine. Microscopic examination is the gold standard for the detection of microscopic hematuria (defined as ≥3 RBCs per high-power field). It can also be helpful in distinguishing between glomerular and nonglomerular sources of hematuria. (See 'Glomerular versus nonglomerular hematuria' below.)

Microscopic examination of the urine sediment is most reliable when performed by an experienced examiner. However, the vast majority of urinalyses are processed by clinical laboratories that employ automated urine microscopic analyzers to identify cells and particles in urine. Automated analyzers accurately identify RBCs in the urine but are not reliable in distinguishing RBC morphology (eg, isomorphic RBCs versus dysmorphic RBCs).  

A discussion of the proper technique for preparing and examining the urine sediment is presented separately. (See "Urinalysis in the diagnosis of kidney disease", section on 'Urine sediment technique'.)

Confirming true hematuria

●Confirming microscopic hematuria – Microscopic hematuria is frequently detected as an incidental finding on a urinalysis or dipstick. As discussed above, a positive dipstick for blood should always be confirmed by microscopic examination of the urine sediment. This can help reduce the unnecessary evaluation of patients without true microscopic hematuria [4]. (See 'Detection of hematuria' above.)

There is no consensus on how many urinalyses are needed to confirm the presence of microscopic hematuria. The 2020 American Urological Association (AUA) guidelines state that a single urinalysis with ≥3 RBCs per high-power field is sufficient to diagnose microscopic hematuria [5]. We repeat the urinalysis at least once for confirmation.

●Confirming gross hematuria – Red to brown colored urine can be caused by a variety of conditions other than bleeding into the urinary tract, including the following (see "Urinalysis in the diagnosis of kidney disease", section on 'Red to brown urine'):

•Use of certain medications, such as phenazopyridine, rifampin, phenytoin, nitrofurantoin, or hydroxycobalamin

•Consumption of food dyes

•Ingestion of beets (beeturia), rhubarb, or senna

•Acute intermittent porphyria

Thus, the initial step in the evaluation of red to brown urine is to confirm that the discoloration is due to blood or another substance. This can be accomplished by the following two steps:

•Urine dipstick – If the urine dipstick test for blood is positive, the likely cause of the red/brown discoloration is blood or free hemoglobin or myoglobin. A negative test eliminates these etiologies as the cause of urine discoloration.

•Urine centrifugation – After centrifugation of the urine, if the sediment is red/brown, then the etiology is most likely blood (algorithm 1). Microscopic examination of the sediment should confirm the presence of RBCs. If the supernatant is red/brown and the sediment is not discolored, then the red/brown urine is not due to blood but to another substance, such as free hemoglobin or myoglobin. How these disorders can be distinguished is discussed elsewhere. (See "Urinalysis in the diagnosis of kidney disease", section on 'Hemoglobinuria and myoglobinuria'.)

Glomerular versus nonglomerular hematuria — Distinguishing between glomerular and other sources of hematuria is important in guiding the evaluation of hematuria. Patients with clear evidence of glomerular hematuria may not need to be evaluated for potentially serious urologic disease unless there is some other reason to do so. Although the identification of dysmorphic RBCs, proteinuria, cellular casts, and/or kidney function impairment warrants a nephrologic evaluation, it does not necessarily preclude the need for a urologic workup.

Glomerular hematuria may result from immune-mediated injury to the glomerular capillary wall or, in noninflammatory glomerulopathies such as thin basement membrane nephropathy, from localized gaps in the glomerular capillary wall [6].

Signs of glomerular bleeding (best identified by a nephrologist or other experienced examiner) include the following (table 1):

●RBC casts – The presence of red blood cell (RBC) casts (picture 2) seen by urine microscopy is virtually diagnostic of glomerulonephritis or vasculitis, although such casts are seen in acute interstitial nephritis on rare occasion. The absence of these casts, however, does not exclude glomerular hematuria.

●Dysmorphic RBCs – RBCs seen by urine microscopy are typically uniform and round (as in a peripheral blood smear) with extrarenal bleeding, but they usually have a dysmorphic appearance with kidney lesions [7-9], particularly but not only in glomerular diseases (picture 3A) [9]. This change in morphology is manifested by blebs, budding, and segmental loss of membrane, resulting in marked variability in RBC shape and a reduction in mean RBC size (picture 3B) [10]. RBC injury in this setting may be due both to mechanical trauma as the cells pass through rents in the glomerular basement membrane and to osmotic trauma as the cells flow through the nephron [11]. The proportion of RBCs with a dysmorphic appearance that is required to diagnose glomerular hematuria varies widely from ≥3 to 90 percent; a reasonable number to employ is ≥40 percent [12].

Optimal assessment of RBC morphology requires phase-contrast microscopy [13], which is not generally available in a clinician's office and which requires experience in its use to gain proficiency.

●Acanthocytes – The type of dysmorphic RBC may be of diagnostic importance. While dysmorphic RBCs alone may be predictive of only renal bleeding, acanthocytes (ring-shaped RBCs with vesicle-shaped protrusions that are best seen on phase-contrast microscopy) appear to be most predictive of glomerular disease (picture 3A-B) [13,14]. In one study, for example, the presence of acanthocytes comprising ≥5 percent of excreted RBCs had a sensitivity and specificity for glomerular disease of 52 and 98 percent, respectively [13]. Regardless of the absolute number or percentage, the presence of acanthocytes in the urine should lead the clinician to consider nephrology consultation rather than a lengthy urological evaluation.

●Brown or cola-colored urine – A change in the urine color with gross hematuria may also be helpful. The urine is typically red to pink with nonglomerular bleeding. Although red urine also may be seen with glomerular bleeding (particularly in alkaline urine), the combination of prolonged transit time through the nephron and an acid urine pH may result in the formation of methemoglobin, which has a smoky brown or cola color. (See "Urinalysis in the diagnosis of kidney disease", section on 'Red to brown urine'.)

●Proteinuria – Proteinuria (and, more specifically, albuminuria) that is temporally related to the hematuria is suggestive of glomerular disease. Proteinuria tends to be higher in patients with glomerular hematuria than in patients with nonglomerular hematuria, but considerable overlap exists, such that mild to moderate proteinuria can be seen with both glomerular and nonglomerular hematuria. However, a higher percentage of urine protein in the form of albumin is consistent with glomerular hematuria [15].

The diagnostic importance of proteinuria varies with the time of onset. If, for example, the patient has previously identified proteinuria well before the onset of hematuria, then a separate disease may be responsible for the hematuria.

Microscopic hematuria alone does not typically lead to a significant increase in protein excretion. A dipstick test for protein that is greater than 1+ is rarely observed with nonglomerular bleeding, even with gross hematuria, unless the amount of gross blood is very large. Extremely bloody urine, especially with clots, should trigger an evaluation for a nonglomerular source even if abnormal proteinuria is present. (See "Evaluation of proteinuria in adults".)

●Impaired kidney function – A rise in serum creatinine (or reduction in estimated glomerular filtration rate [eGFR]) that is temporally related to the hematuria may be a sign of glomerular disease. However, acute kidney injury can also be seen with urinary obstruction due to a kidney/ureteral stone or blood clots.

●Absence of blood clots – Blood clots, if present, are almost always due to nonglomerular bleeding [16]. They are indicative of heavy focal bleeding in which whole blood is shed into the urine in amounts sufficient to support clot formation.

Transient hematuria — Transient microscopic hematuria is a common problem in adults [17-20]. The following observations illustrate the range of findings:

●In a prospective cohort study including 2,421,585 members (of all ages) of a managed care organization with at least one urinalysis, 967,297 (40 percent) had asymptomatic microscopic hematuria [20]. Of these, a second urinalysis was positive for microscopic hematuria in 643,304 (66 percent). Thus, approximately one-third of individuals with an initially positive urinalysis had transient hematuria.

●Another study evaluated 1000 young males who had yearly urinalyses between the ages of 18 and 33 years; hematuria was seen in 39 percent on at least one occasion and 16 percent on two or more occasions [17].

No obvious etiology can be identified in most patients with transient hematuria. Fever, infection, menses, trauma, exercise, and recent instrumentation (eg, urinary catheterization) are potential causes of transient hematuria. (See "Exercise-induced hematuria".)

Transient hematuria can also occur with urinary tract infection (eg, cystitis). In this setting, hematuria is typically accompanied by pyuria and bacteriuria, and patients often complain of dysuria. A potential source of error is that dysuria (but not pyuria and bacteriuria) can also be seen with macroscopic hematuria from bladder cancer.

An important exception to the typically benign nature of transient hematuria occurs in patients at high risk for malignancy, in whom even transient hematuria carries an appreciable association with malignancy (assuming there is no evidence of glomerular bleeding) [2,18,19,21-24]. As an example, screening studies limited to healthy males over the age of 50 to 60 years found that 8 to 9 percent of patients with intermittent asymptomatic hematuria, as detected by a dipstick for heme, had a urinary tract malignancy [23,24]. (See 'Follow-up of transient hematuria' below.)

CAUSES OF HEMATURIA — 

Hematuria may be a symptom of an underlying disease, some of which are life threatening and some of which are treatable (figure 1). The causes vary with age, with the most common being inflammation or infection of the bladder, stones, and, in older patients, a kidney or urinary tract malignancy or benign prostatic hyperplasia (BPH) (figure 2) [2,19,22,25-29].

RISK FACTORS FOR MALIGNANCY — 

The 2025 American Urological Association (AUA) guidelines on microscopic hematuria included the following risk factors for urothelial malignancy [1]:

●Male sex

●Older age (≥60 years for females and ≥40 years for males)

●Past or current smoking history in which the risk correlates with the extent of exposure

●Occupational exposure to chemicals or dyes (benzenes or aromatic amines), such as printers, painters, and chemical plant workers

●Degree of microscopic hematuria

●Persistence of microscopic hematuria

●History of gross hematuria

●History of irritative voiding symptoms

●History of chronic urinary tract infection

●History of pelvic irradiation

●History of exposure to cyclophosphamide or ifosfamide

●History of a chronic indwelling foreign body

●History of exposure to aristolochic acid

●History of heavy non-narcotic analgesic use, which is also associated with an increased incidence of carcinoma of the kidney

●Family history of urothelial carcinoma or Lynch syndrome

●Sickle cell trait/sickle cell disease (not included in the AUA guidelines but associated with renal medullary carcinoma, especially sickle cell trait) (see "Sickle cell trait", section on 'Renal medullary carcinoma')

The 2025 AUA guidelines also introduced a revised risk stratification system to categorize patients evaluated for microscopic hematuria as being low/negligible-, intermediate-, or high-risk for developing urothelial cancer (algorithm 2) [1]. Risk categories were based on factors such as age, sex, smoking and other urothelial cancer risk factors, degree and persistence of microscopic hematuria, and prior gross hematuria. The aim of this stratification system was to limit the unnecessary risk and cost associated with “over-evaluation” of patients at low to intermediate risk for urothelial cancer, while simultaneously avoiding “under-evaluation” of patients at high risk. Several studies have validated the ability of the AUA system to define distinct patient groups that have differing degrees of risk of urothelial malignancy [30-32]. (See 'Asymptomatic patients' below.)

Several studies have illustrated the importance of gross (visible) hematuria and older age on cancer risk:

●In a prospective cohort study of 4414 members of a managed care organization with unexplained, asymptomatic microscopic hematuria who were referred for urologic evaluation, 111 cancers were identified (2.5 percent); 100 were bladder cancers, and 11 were renal cancers [20]. However, the prevalence of malignancy was 11.2 percent among patients 50 years or older who also had a history of gross hematuria plus at least one additional risk factor (male sex, smoking, or more than 25 red blood cells [RBCs] per high-power field). By contrast, the prevalence of cancer was 0.2 percent among patients younger than 50 years who did not have a history of gross hematuria. This study suggests that individuals at low risk for malignancy (ie, with none of the risk factors listed above) who have asymptomatic microscopic hematuria may not require a urologic referral.

●In another study of 1930 patients (mean age of 58 years, 62 percent male) who were referred to a hematuria clinic because of gross or microscopic hematuria, 12 percent had bladder cancer, 0.7 percent had kidney and upper tract tumors, and 61 percent had no cause identified [21]. In addition:

•At age 50 to 59 years, malignancy was identified in 20.4 versus 1.9 percent of males with macroscopic versus microscopic hematuria, respectively, and in 8.9 versus 1.9 percent of females with macroscopic versus microscopic hematuria, respectively.

•At age 60 to 69 years, malignancy was found in 28.9 versus 7.9 percent of males with macroscopic versus microscopic hematuria, respectively, and 21.1 versus 4.5 percent of females with macroscopic versus microscopic hematuria, respectively.

The risk factors for bladder and renal cell carcinomas are discussed in detail separately. (See "Epidemiology and risk factors of urothelial carcinoma of the bladder" and "Epidemiology, pathology, and pathogenesis of renal cell carcinoma", section on 'Established risk factors'.)

INITIAL EVALUATION — 

The initial evaluation of patients with confirmed hematuria includes a targeted history, physical examination, and laboratory testing to identify potential causes and risk factors for hematuria and to determine whether further evaluation and referral to a specialist (nephrology or urology) are warranted.

History — We perform a targeted history to identify potential causes and risk factors for hematuria, with a focus on the following elements:

●History of gross hematuria – All patients should be assessed for the presence or absence of gross (visible) hematuria. In patients with gross hematuria, we ask about the color and appearance of the urine, number and frequency of past episodes, and presence or absence of visible blood clots. Blood clots, if present, are almost always due to nonglomerular bleeding. (See 'Glomerular versus nonglomerular hematuria' above.)

The point at which gross hematuria is noted during urination may be helpful in localizing its source [33]:

•Hematuria occurring primarily at the beginning of urination is usually from a urethral source.

•Blood that is only noticed as a discharge between voidings or as a stain on undergarments, while the voided urine itself appears clear, indicates an origin at the urethral meatus or the anterior urethra.

•Terminal hematuria, with blood appearing towards the end of voiding, generally originates from the bladder neck or prostatic urethra.

•Hematuria occurring throughout voiding can originate from anywhere in the urinary tract, including the bladder, ureters, or kidneys.

●Associated symptoms – We assess for the presence of associated symptoms, such as:

•Unilateral flank pain (which may radiate to the groin), which usually suggests ureteral obstruction due to a stone or blood clot but can occasionally be seen with malignancy or IgA nephropathy.

•Dysuria with or without fever, which is usually indicative of a urinary tract infection but may also occur with bladder malignancy or sexually transmitted disease.

•Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). The cellular proliferation in BPH is associated with increased vascularity, and the new vessels can be fragile. This can lead to mild hematuria. (See "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia", section on 'Clinical manifestations'.)

•A recent upper respiratory infection or symptoms of upper respiratory disease, which raise the possibility of postinfectious or infection-related glomerulonephritis, IgA nephropathy, vasculitis, anti-glomerular basement membrane (GBM) disease, or sometimes Alport syndrome.

•Systemic symptoms, such as fever, rash, joint pain, or weight loss, which might suggest a systemic condition associated with glomerular disease (eg, systemic lupus erythematosus [SLE] or IgA vasculitis [Henoch-Schönlein purpura]). Recent weight loss that is not deliberate may also suggest an occult malignancy.

●Causes of transient hematuria – We ask about recent events that can be associated with transient hematuria, such as menses (in females), vigorous exercise (eg, long-distance running), acute trauma (eg, riding a motorcycle), or recent instrumentation (eg, urinary catheterization or cystoscopy). Cyclic hematuria in females that is most prominent during and shortly after menstruation suggests endometriosis of the urinary tract [34]. (See 'Transient hematuria' above.)

●Risk factors for malignancy – We assess the patient for risk factors for bladder and kidney cancer. (See 'Risk factors for malignancy' above.)

●Comorbid health conditions – We assess the patient for other comorbid health conditions that can be associated with hematuria, such as:

•Sickle cell trait or disease in Black patients, which can lead to papillary necrosis and hematuria, as well as renal medullary carcinoma. (See 'Patients with sickle cell trait/disease' below and "Sickle cell trait", section on 'Urologic complications' and "Sickle cell trait", section on 'Renal medullary carcinoma' and "Sickle cell disease effects on the kidney", section on 'Hematuria and/or flank pain'.)

•A history of bleeding disorder or bleeding from multiple sites due to excessive anticoagulation therapy. However, clinicians should not assume that hematuria alone can be explained by chronic anticoagulation therapy. (See 'Patients on antiplatelet or anticoagulant therapy' below.)

•A history of kidney stones. Patients with existing kidney stones may have ongoing microscopic hematuria. However, clinicians should not assume that hematuria in such patients is necessarily due to kidney stones. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Hematuria'.)

•A history of kidney disease, such as IgA nephropathy, Alport syndrome, thin basement membrane nephropathy (TBMN), or polycystic kidney disease (ADPKD). Patients with IgA nephropathy, Alport syndrome, or TBMN may have persistent isolated hematuria that may not necessitate further workup. Hematuria in patients with ADPKD may be caused by rupture of a cyst into the collecting system or nephrolithiasis.

●Medications – We review the patient’s medications for agents that may cause hematuria, including the following:

•Cyclophosphamide, which can cause hemorrhagic cystitis or bladder cancer. (See "Cyclophosphamide in rheumatic diseases: General principles of use and toxicity", section on 'Bladder toxicity'.)

•Analgesics (eg, phenacetin), which can cause papillary necrosis or urothelial cancer. (See "Clinical manifestations and diagnosis of analgesic nephropathy" and "Urinary tract malignancy and atherosclerotic disease in patients with chronic analgesic misuse".)

•Drugs that cause acute or chronic interstitial nephritis, such as nonsteroidal antiinflammatory drugs (NSAIDs), penicillins and cephalosporins, proton pump inhibitors, rifampin, sulfonamides, and diuretics. (See "Clinical manifestations and diagnosis of acute interstitial nephritis", section on 'Drugs'.)

•Drugs that may promote kidney stone formation, such as carbonic anhydrase inhibitors (table 2). (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Medications'.)

Antiplatelet agents and anticoagulants may make hematuria appear more pronounced but should not be assumed to be the sole cause of hematuria in patients taking these medications. (See 'Patients on antiplatelet or anticoagulant therapy' below.)

●Family history – We assess for any family history of kidney stones, kidney disease (eg, Alport syndrome, polycystic kidney disease) or kidney or bladder cancer. (See 'Patients with a family history of kidney cancer' below.)

●Infectious exposures – We ask about travel or residence in areas endemic for Schistosoma haematobium or tuberculosis, infectious agents that can cause genitourinary manifestations including hematuria. (See "Schistosomiasis: Epidemiology and clinical manifestations", section on 'Genitourinary schistosomiasis' and "Urogenital tuberculosis", section on 'Renal and urologic tuberculosis'.)

Physical examination — Physical examination should be guided by the clinical history and may include the following assessments:

●Blood pressure measurement – New or worsening hypertension may be seen in patients with glomerular disease and other underlying kidney disease. Hypotension or orthostatic hypotension may be observed in patients with heavy gross hematuria and clinically significant anemia.

●Assessment for edema – New or worsening edema and recent weight gain could suggest underlying glomerular disease.

●Abdominal exam – The presence of costovertebral angle tenderness or suprapubic tenderness could suggest a kidney stone or urinary tract infection. The abdomen should also be palpated for masses.

●Skin exam – The skin should be examined for new rashes or purpura that could suggest a systemic condition associated with glomerular disease (eg, SLE or IgA vasculitis [Henoch-Schönlein purpura]). (See "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", section on 'Mucocutaneous involvement' and "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Skin manifestations'.)

●Genitourinary exam – In male patients, an examination of the genitals may identify urethral lesions that could explain hematuria. In addition, a rectal examination with palpation of the prostate may be helpful in assessing for prostate enlargement, prostatitis, or prostate cancer. In female patients, examination of the external genitalia, introitus, and periurethral tissue may help to detect urethral or other gynecologic lesions that could cause hematuria.

Laboratory testing — We obtain the following laboratory tests as part of the initial evaluation:

●Urinalysis and examination of the sediment – A urinalysis should be performed to confirm persistent hematuria, evaluate for signs of urinary tract infection, and check for the presence of proteinuria. (See 'Confirming true hematuria' above.)

•If there are signs of urinary tract infection (eg, white blood cells [WBCs] in the urine, positive dipstick for leukocyte esterase and/or nitrite), we obtain a urine culture to confirm infection.

•If proteinuria is present (ie, 1+ or greater) on dipstick, we quantify the proteinuria, either with a spot urine protein-to-creatinine ratio (UPCR) or urine albumin-to-creatinine ratio (UACR). (See "Evaluation of proteinuria in adults", section on 'Quantitative measurement'.)

Microscopic examination of the urine sediment, if performed by an experienced examiner (eg, a nephrologist), can suggest a potential site of bleeding (glomerular versus nonglomerular) (see 'Glomerular versus nonglomerular hematuria' above). However, many clinical laboratories employ automated urine microscopic analyzers to identify cells and particles in urine; these platforms have not been shown to be as reliable as trained clinicians to distinguish RBC morphology. Clinicians should not rely upon the results of automated urine microscopy to identify signs of glomerular bleeding. If an experienced examiner is not available, referral to a nephrologist is reasonable while urologic sources of bleeding are also considered. (See "Urinalysis in the diagnosis of kidney disease", section on 'Urine sediment technique'.)

●Basic metabolic panel – A basic metabolic panel should be obtained to assess kidney function (serum creatinine and estimated glomerular filtration rate [eGFR]).

WHEN TO REFER TO THE EMERGENCY DEPARTMENT — 

Isolated hematuria rarely represents a true emergency unless non-glomerular hematuria is so brisk that it results in significant or symptomatic anemia or blood clots obstruct the ureter(s) or bladder outflow (ie, urethra). We refer the following patients to the emergency department for more immediate evaluation and management:

●Patients with gross (visible) hematuria and visible blood clots who are experiencing symptoms of urinary tract obstruction or urinary retention (eg, anuria, lower abdominal pain). (See 'Gross (visible) hematuria' below and "Management of acute gross hematuria in adults", section on 'Assess for bladder outflow obstruction'.)

●Patients with gross hematuria and symptoms and signs of clinically significant anemia, including tachycardia, pallor, hypotension, orthostasis, dyspnea, chest pain, and lightheadedness. (See "Management of acute gross hematuria in adults", section on 'Assess for anemia or shock'.)

●Patients with gross hematuria and severe flank or abdominal pain, as they may have obstructive nephrolithiasis. (See 'Gross (visible) hematuria' below.)

DIAGNOSTIC APPROACH BASED ON INITIAL EVALUATION — 

Subsequent evaluation of the patient is guided by the clinical presentation and the findings of the initial evaluation. (See 'Initial evaluation' above.)

Gross (visible) hematuria — In patients presenting with gross hematuria, we take the following diagnostic approach (algorithm 3):

●Visible blood clots present – Patients who have visible blood clots in the urine require more urgent evaluation as these clots may lead to urinary tract obstruction and urinary retention.

•Nonpregnant patients – In nonpregnant patients with visible blood clots in the urine, we obtain computed tomography (CT) of the abdomen and pelvis without and with contrast for urography, also called CT urography (CTU), and refer the patient for urgent urology evaluation for cystoscopy and further workup. If CTU cannot be performed, magnetic resonance urography (MRU) is a reasonable alternative. (See 'Imaging studies' below and 'Cystoscopy' below.)

•Pregnant patients – In pregnant patients with visible blood clots in the urine, the preferred imaging study is kidney and bladder ultrasound rather than CTU, largely to rule out ureteral obstruction or urolithiasis. If ultrasound demonstrates hydronephrosis, MRU without contrast is used to localize the point of obstruction. Since hematuria as a symptom of malignancy is exceedingly rare in pregnant patients, further evaluation with CTU and cystoscopy should be deferred, if possible, until after delivery. For those at higher risk of malignancy (eg, older age, past or current smoking history), cystoscopy can be considered during pregnancy based on shared decision making. (See 'Imaging studies' below.)

●No visible blood clots – If the patient does not have visible blood clots in the urine, our approach is as follows:

•Patients with acute flank pain – In patients who present with acute unilateral flank pain suggestive of obstructive nephrolithiasis, we obtain imaging (noncontrast computed tomography [CT] or ultrasound with or without an abdominal radiograph) to evaluate for ureteral obstruction due to a stone. The evaluation of suspected nephrolithiasis is discussed in detail separately. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Diagnostic imaging'.)

If imaging does not identify a urinary stone as the source of hematuria, the patient should be evaluated for other possible causes of hematuria, as discussed below for all other patients.

•Patients with findings suggestive of UTI – In patients with findings suggestive of urinary tract infection (UTI; eg, dysuria, fever, presence of white blood cells [WBCs] in the urine, positive dipstick for nitrite), we obtain a urine culture to evaluate for UTI. In patients with UTI, the infection should be treated and the urinalysis should be repeated approximately six weeks after completion of antibiotic therapy in order to determine if the hematuria is persistent. If the repeat urinalysis is negative for microscopic hematuria, we attribute the hematuria to the UTI and discontinue further evaluation. If the repeat urinalysis is positive for microscopic hematuria, the patient should proceed to further evaluation for persistent hematuria.

•Patients with findings suggestive of glomerular hematuria – In patients who have any findings suggestive of glomerular hematuria (eg, red blood cell [RBC] casts, dysmorphic RBCs, proteinuria, impaired kidney function), we refer to nephrology for further evaluation and management. Such evaluation may involve additional laboratory testing and possibly a kidney biopsy to obtain a definitive diagnosis. However, a nephrologic evaluation does not necessarily preclude the need for a urologic workup. If a glomerular cause of hematuria is not identified and the patient has persistent hematuria, the patient should be evaluated for urologic sources of hematuria. (See 'Glomerular versus nonglomerular hematuria' above and "Glomerular disease: Evaluation and differential diagnosis in adults", section on 'Glomerular hematuria'.)

•All other patients – Most adults presenting with gross (visible) hematuria who do not have visible blood clots, a UTI, suspected nephrolithiasis, or suspected glomerular hematuria should have imaging of the urinary tract and referral to urology for cystoscopy, given the high risk of urothelial cancer in this population [1]. (See 'Risk factors for malignancy' above.)

-Nonpregnant patients – For nonpregnant patients, the preferred imaging study is CTU. If CTU cannot be performed, MRU is a reasonable alternative. (See 'Imaging studies' below.)

All nonpregnant patients with gross hematuria and no evidence of UTI, nephrolithiasis, or glomerular disease should undergo cystoscopy. Cystoscopy permits direct visualization of the bladder and can detect malignant or other sources of bleeding. (See 'Cystoscopy' below.)

-Pregnant patients – For pregnant patients, the preferred imaging study is kidney and bladder ultrasound rather than CTU, largely to rule out ureteral obstruction or urolithiasis. If ultrasound demonstrates hydronephrosis, MRU without contrast is used to localize the point of obstruction. Since hematuria as a symptom of malignancy is exceedingly rare in pregnant patients, further evaluation with CTU and cystoscopy should be deferred, if possible, until after delivery. For those at higher risk of malignancy (eg, older age, past or current smoking history), cystoscopy can be considered during pregnancy based on shared decision making. (See 'Imaging studies' below.)

The acute management of patients with ongoing or recent gross hematuria is discussed separately. (See "Management of acute gross hematuria in adults".)

Microscopic hematuria — In patients who have microscopic hematuria without gross hematuria, the approach differs depending upon whether or not the patient has additional symptoms associated with the hematuria. (See 'History' above.)

Symptomatic patients — In patients with microscopic hematuria who have associated symptoms (see 'History' above), our subsequent evaluation is guided by the specific symptoms (algorithm 2):

●Acute flank pain – In patients who present with acute unilateral flank pain suggestive of obstructive nephrolithiasis, we obtain imaging (noncontrast CT or ultrasound with or without an abdominal radiograph) to evaluate for ureteral obstruction due to a stone. The evaluation of suspected nephrolithiasis is discussed in detail separately. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Diagnostic imaging'.)

If imaging does not identify a urinary stone as the source of hematuria, the patient should be evaluated for other possible causes of hematuria.

●Dysuria with or without fever – In patients with dysuria with or without fever, we obtain a urine culture to evaluate for UTI. In patients with UTI, the infection should be treated and the urinalysis should be repeated approximately six weeks after completion of antibiotic therapy in order to determine if the hematuria is persistent. If the repeat urinalysis is negative for microscopic hematuria, we attribute the hematuria to the UTI and discontinue further evaluation. If the repeat urinalysis is positive for microscopic hematuria, the patient should proceed to further evaluation for persistent hematuria.

●Obstructive symptoms – Patients with hematuria and lower urinary tract symptoms (LUTS) should be referred to urology. Such patients are typically evaluated with imaging and cystoscopy. (See "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia" and "Clinical presentation and diagnosis of prostate cancer", section on 'Symptoms'.)

●Recent upper respiratory infection or symptoms of upper respiratory disease – Patients with hematuria and a recent upper respiratory infection or upper respiratory symptoms should have their kidney function assessed and, if abnormal, should be referred to nephrology. Such patients may require additional laboratory testing and possibly a kidney biopsy to obtain a definitive diagnosis. (See 'Kidney biopsy' below and "Glomerular disease: Evaluation and differential diagnosis in adults", section on 'Glomerular hematuria'.)

●Systemic symptoms – Patients who present with hematuria and systemic symptoms (eg, fever, rash, joint pain, or weight loss) that suggest a systemic condition associated with glomerular disease should be referred to nephrology. Such patients may require additional laboratory testing and possibly a kidney biopsy to obtain a definitive diagnosis. (See 'Kidney biopsy' below and "Glomerular disease: Evaluation and differential diagnosis in adults", section on 'Glomerular hematuria'.)

Asymptomatic patients — In patients with asymptomatic microscopic hematuria, we take the following approach (algorithm 2):

●Patients with a potential cause of transient hematuria – In patients with asymptomatic microscopic hematuria who have a potential cause of transient hematuria (menses, vigorous exercise, acute trauma, or recent instrumentation), we repeat the urinalysis to determine if hematuria is persistent. (See 'Transient hematuria' above.)

•In menstruating females, the urinalysis should be repeated later in the cycle once menstrual bleeding has ceased. If this is not possible, a tampon can be inserted, and urinalysis can be obtained after the perineum is cleansed.

•In patients who had hematuria identified in the setting of vigorous exercise, the urinalysis should be repeated approximately four to six weeks later during a period of no exercise.

•Patients with acute trauma and microscopic hematuria should have a confirmatory urinalysis after six weeks.

•Patients with hematuria identified after recent instrumentation should have a repeat urinalysis in one to two weeks.

If the repeat urinalysis is negative for microscopic hematuria, the patient has transient hematuria. Additional follow-up is advised for patients with transient hematuria if they are at high risk for urothelial malignancy. (See 'Follow-up of transient hematuria' below.)

If the repeat urinalysis is positive for microscopic hematuria, the patient should proceed to further evaluation for persistent hematuria.

●Patients with findings suggestive of UTI – In asymptomatic patients with findings suggestive of UTI (eg, presence of WBCs in the urine, positive dipstick for nitrite), we obtain a urine culture to evaluate for UTI. In patients with UTI, the infection should be treated and the urinalysis should be repeated approximately six weeks after completion of antibiotic therapy in order to determine if the hematuria is persistent. If the repeat urinalysis is negative for microscopic hematuria, we attribute the hematuria to the UTI and discontinue further evaluation. If the repeat urinalysis is positive for microscopic hematuria, the patient should proceed to further evaluation for persistent hematuria.

●Patients with findings suggestive of glomerular hematuria – In patients who have any findings suggestive of glomerular hematuria (eg, RBC casts, dysmorphic RBCs, proteinuria, impaired kidney function), we refer to nephrology for further evaluation and management. Such evaluation may involve additional laboratory testing and possibly a kidney biopsy to obtain a definitive diagnosis. However, a nephrologic evaluation does not necessarily preclude the need for a urologic workup. If a glomerular cause of hematuria is not identified and the patient has persistent hematuria, the patient should be evaluated for urologic sources of hematuria, as discussed in the bullet below. (See 'Glomerular versus nonglomerular hematuria' above and "Glomerular disease: Evaluation and differential diagnosis in adults", section on 'Glomerular hematuria'.)

●All other patients – In all other patients, the diagnostic evaluation is directed to the kidneys, ureters, bladder, urethra, and prostate. Imaging of the kidney, ureters, and bladder should be combined with cystoscopy, which is more sensitive for detection of bladder and urethral lesions.

Our approach, which is largely consistent with the 2025 guidelines from the American Urologic Association (AUA), is guided by an assessment of the patient’s risk of urothelial cancer (algorithm 2) [1]. The rationale for this approach is to limit the unnecessary risk and cost associated with “over-evaluation” of patients at low risk for urothelial cancer, while simultaneously avoiding “under-evaluation” of patients at high risk.

An exception to this risk stratification system is in patients with sickle cell trait, those with a family history of kidney cancer, those with a genetic kidney tumor syndrome (eg, von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell cancer [HLRCC], tuberous sclerosis), or those with a personal or family history of (or suspicious for) Lynch syndrome; such patients should have imaging of the upper urinary tract regardless of their risk category. (See 'Patients with sickle cell trait/disease' below and 'Patients with a family history of kidney cancer' below.)

•High risk – In patients at high risk for malignancy (algorithm 2), we obtain axial imaging of the upper urinary tract and refer to urology for cystoscopy. In studies that have evaluated the AUA risk stratification system, high risk patients have been found to have a 1.3 to 6.3 percent risk of urothelial malignancy [30-32].

-Nonpregnant patients – For most nonpregnant high-risk patients, CTU is the preferred imaging modality, unless contraindicated. For patients who cannot undergo CTU, MRU is a reasonable alternative. If the patient is unable to undergo CTU and MRU, retrograde pyelography (to assess the upper urinary tracts) in conjunction with noncontrast CT or kidney ultrasound (to assess the kidney cortex) is another option. (See 'Imaging studies' below.)

All nonpregnant high-risk patients should undergo cystoscopy given the high risk of bladder cancer in this population. Cystoscopy permits direct visualization of the bladder and can detect malignant or other sources of bleeding. (See 'Cystoscopy' below.)

-Pregnant patients – For pregnant high-risk patients, kidney and bladder ultrasound is the preferred imaging modality rather than CTU, largely to rule out ureteral obstruction or urolithiasis. Since hematuria as a symptom of malignancy is exceedingly rare in pregnant patients, further evaluation with CTU and cystoscopy should be deferred, if possible, until after delivery. For those at higher risk of malignancy (eg, older age, past or current smoking history), cystoscopy can be considered during pregnancy based on shared decision making. (See 'Imaging studies' below.)

•Intermediate risk – In patients at intermediate risk for malignancy (algorithm 2), we obtain kidney and bladder ultrasound and refer to urology for cystoscopy. In studies that have evaluated the AUA risk stratification system, intermediate risk patients have been found to have a 0.2 to 3.1 percent risk of urothelial malignancy [30-32].

-In intermediate-risk patients, kidney and bladder ultrasound is the preferred imaging modality because of its adequate sensitivity and specificity for kidney cortical tumors compared with axial imaging, particularly given the low incidence of these cancers in this population. In addition, ultrasound is favored due to its lower cost and associated risks (eg, radiation exposure, intravenous contrast reactions). (See 'Imaging studies' below.)

-All nonpregnant intermediate-risk patients should undergo cystoscopy. In pregnant intermediate-risk patients, cystoscopy should be deferred, if possible, until after delivery due to the potential complications of this procedure, particularly urinary tract infection. Studies of patients with microscopic hematuria have shown that when a urologic malignancy is detected during evaluation, the most frequent cancer is bladder cancer [35-38]. (See 'Cystoscopy' below.)

Some appropriately counseled intermediate-risk patients may wish to avoid cystoscopy given its potential for causing patient anxiety and discomfort. In such patients, clinicians can offer urine cytology or validated urine-based tumor markers (CxBladder Resolve, CxBladder Triage, nuclear matrix protein 22 [NMP22], UroVysion, Xpert Bladder Cancer Detection) to assist in decisions regarding the utility of cystoscopy [1]. In studies of patients with microscopic hematuria, these urine tests have a negative predictive value (NPV) of 95 to 100 percent for the detection of bladder cancer [39-48]; patients with negative testing have a low likelihood of having bladder cancer and may choose to forego cystoscopy. If cystoscopy is not performed, a kidney and bladder ultrasound should still be performed to evaluate the upper urinary tract, and a urinalysis should be repeated within 12 months [1]. If the repeat urinalysis shows persistent hematuria, the patient should be advised to undergo cystoscopy. (See 'Urine cytology and biomarkers' below and "Urine biomarkers for the detection of urothelial (transitional cell) carcinoma of the bladder".)

•Low/negligible risk – In patients at low/negligible risk for malignancy (algorithm 2), we repeat a urinalysis within six months. Routine cystoscopy and imaging are not advised for these patients given their very low rates of urothelial malignancy (0 to 0.4 percent) in studies that have evaluated the AUA risk stratification system [30-32].

If the repeat urinalysis is negative, we consider the patient to have a negative evaluation. If the repeat urinalysis shows persistent microscopic hematuria, the patient should be reclassified as intermediate or high risk based on the degree of microscopic hematuria on urinalysis and other risk factors and should be evaluated accordingly. In one study of over 11,000 patients, patients with persistent microscopic hematuria on repeat urine testing had a higher rate of urothelial cancer on subsequent evaluation compared with those who had negative repeat urine testing [38].

Follow-up of patients after a negative evaluation is discussed below. (See 'Follow-up of persistent hematuria' below.)

DIAGNOSTIC TESTS

Imaging studies — Urinary tract imaging studies may be used in the evaluation of hematuria in adults. A brief description and the diagnostic utility of these modalities are summarized below; proper selection among these modalities is presented above. (See 'Diagnostic approach based on initial evaluation' above.)

●CT urography – Computed tomography (CT) of the abdomen pelvis without and with intravenous contrast for urography, also called CTU, is the preferred imaging modality in patients with unexplained hematuria who are at high risk of malignancy [1,49].

CTU combines the cross-sectional imaging of CT with an image acquisition protocol tailored to evaluate for nephrolithiasis and urothelial tumors. Although CTU protocols vary slightly with each site, in general, images of the kidney and the urinary collecting system are first obtained precontrast; after the administration of contrast, images are then obtained in the renal parenchymal phase and the excretory phase, either concurrently or successively. The noncontrast imaging evaluates for nephrolithiasis and hydronephrosis; the postcontrast imaging evaluates for renal and urothelial malignancy and, in the context of hydronephrosis, impaired function of the obstructed kidney. Thus, CTU provides anatomic and functional imaging of the kidneys, ureters, and bladder.

CTU is more accurate than intravenous pyelogram (IVP) or ultrasound for the diagnosis of renal masses, urinary tract calculi, and pelvicalyceal and ureteric transitional cell carcinomas [50-60]. A meta-analysis of CTU yielded a pooled sensitivity of 96 percent (95% CI 88–100) and pooled specificity of 99 percent (95% CI 98–100) for detection of urothelial malignancy.

●Ultrasound of the kidneys and bladder – Ultrasound of the kidneys and bladder, when compared with CTU, demonstrates lower diagnostic yield and is less sensitive in detecting urothelium transitional cell carcinoma, small renal masses, and calculi [51,58,61]. However, when compared with IVP, ultrasound demonstrates higher sensitivity for the diagnosis of upper urinary tract causes of hematuria (25 versus 96 percent). The relative insensitivity of ultrasound in detecting small renal tumors was best shown in a study in which ultrasound detected only 26, 60, 82, and 85 percent of CT-confirmed lesions less than 1 cm, between 1 and 2 cm, between 2 and 3 cm, and 3 cm or more in size, respectively [51].

Ultrasound does not involve ionizing radiation. Hence, it is recommended as the initial imaging examination for hematuria in pregnancy.

For detection of cancer, ultrasound rather than CT is more cost effective when combined with cystoscopy [62]. Some groups outside of the United States prefer ultrasound over CTU as the initial imaging examination in all patients with hematuria [63,64].

●Magnetic resonance urography – MRI of the abdomen and pelvis without and with intravenous contrast for urography, also called MR urography (MRU), is less widely available, and data on diagnostic performance are limited. When compared with CTU, diagnostic accuracy of MRU is comparable in detecting renal lesions but is likely less for urothelial tumors. Stones or calcifications are nearly invisible on MRU. However, MRU, even without contrast, is more sensitive than noncontrast CT in detecting small renal masses and identifying tumors causing hydronephrosis (90 versus 42 percent) [65]. Thus, MRU is useful in patients where iodinated contrast is contraindicated and nephrolithiasis has been excluded or thought unlikely.

MRI does not involve ionizing radiation. Hence, it is useful in localizing the anatomic site of obstruction in pregnant women with hydronephrosis diagnosed on ultrasound.

●Retrograde pyelography – Retrograde pyelography is a fluoroscopic examination where ureters are cannulated during cystoscopy and iodinated contrast is injected retrograde into the ureters. It is usually performed in an outpatient setting under sedation or general anesthesia.

The examination is comparable with CTU in diagnosis of upper tract urothelial tumors. A retrospective study of CTU and retrograde pyelography in diagnosing upper urinary tract urothelial tumors demonstrated sensitivities and specificities of 97 and 93 percent, respectively, for both modalities [59]. In patients with contraindications to intravenous iodinated contrast due to kidney function impairment, retrograde pyelography as an adjunct to cystoscopy is a reasonable option to evaluate the urothelium.

●Intravenous pyelography – Intravenous pyelography (IVP), also called intravenous urography (IVU), is radiographic imaging of the kidneys, ureters, and bladder before and after administration of intravenous iodinated contrast. In addition, postcontrast tomographic images of the kidneys are usually acquired. CTU has largely replaced IVP, which is less sensitive in detecting kidney stones and renal masses (particularly small masses) [51,52].

Cystoscopy — Cystoscopy is an endoscopic technique for examining the internal aspect of the urethra and bladder. It is commonly performed by urologists and is the gold standard for the diagnosis and staging of bladder cancer. The procedure is performed in the office, typically with local anesthesia, with a flexible cystoscopy and has minimal risks, including bleeding and infection. Cystoscopy is associated with the following benefits:

●The entire bladder can be visualized for malignancy or other abnormalities. In the presence of concomitant prostatic hypertrophy, it may be difficult to visualize the entire bladder with video-assisted flexible cystoscopy under local anesthesia. If concerns persist, rigid cystoscopy under spinal or general anesthesia may be required.

●Cystoscopy may identify the source of the bleeding among patients with gross hematuria. It may be possible to determine whether the bleeding is originating from the bladder or from one or both ureters. Unilateral bleeding may be due to an arteriovenous malformation (AVM), fistula, venous varices, or unilateral renal or upper urinary tract tumors or stones [66].

●Cystoscopy is the only modality that permits visualization of the prostate and urethra.

The use of cystoscopy in the diagnosis and staging of bladder cancer is discussed in more detail separately. (See "Clinical presentation, diagnosis, and staging of bladder cancer", section on 'Cystoscopy'.)

Kidney biopsy — A kidney biopsy may be indicated in patients with glomerular hematuria who have risk factors for progressive disease such as proteinuria and/or an elevation in serum creatinine [67-69]. (See "Glomerular disease: Evaluation and differential diagnosis in adults", section on 'Evaluation of glomerulonephritis' and "The kidney biopsy", section on 'Indications'.)

Kidney biopsy is not usually performed for isolated glomerular hematuria (ie, no abnormal proteinuria, no elevation in serum creatinine, no elevation in blood pressure about a previous stable baseline, and no systemic manifestations or family history of kidney disease), since there is no specific therapy for these conditions and since the kidney prognosis is excellent as long as there is no evidence of progressive disease [67,69]. In addition, management of these patients is not usually affected by the biopsy results [69,70]. In one study, for example, the result of the biopsy altered management in only 1 of 36 patients with isolated hematuria compared with 9 of 28 patients with hematuria and proteinuria (3 versus 32 percent) [70]. (See "The kidney biopsy", section on 'Findings that do not require biopsy'.)

When kidney biopsy is performed in such patients, the most common findings are a normal biopsy or one of four disorders: immunoglobulin A (IgA) nephropathy, thin basement membrane disease (benign familial hematuria), mild nonspecific glomerular abnormalities, and Alport syndrome [69]. Among the glomerular diseases, IgA nephropathy is the most common cause worldwide, particularly throughout Asia [71]. (See "Isolated and persistent glomerular hematuria in adults", section on 'Kidney biopsy'.)

Kidney biopsy is also not indicated in patients with persistent, isolated nonglomerular hematuria (ie, no dysmorphic red blood cells [RBCs] or RBC casts, no proteinuria). Such patients, particularly patients with malignancy, need a thorough evaluation with imaging and/or cystoscopy.

Urine cytology and biomarkers — Voided urine cytology has been used historically to evaluate patients with gross and microscopic hematuria but is no longer recommended as part of the initial evaluation due to variable sensitivity and specificity. Some clinicians may obtain urine cytology in high-risk patients with equivocal findings on cystoscopic evaluation or in those with persistent microscopic hematuria and irritative voiding symptoms or risk factors for carcinoma in situ after an initial negative evaluation [1]. (See "Clinical presentation, diagnosis, and staging of bladder cancer", section on 'Urine cytology'.)

Similarly, the use of urine biomarkers for detecting urothelial cancer is not recommended as part of the initial evaluation of hematuria given the lack of supportive data [1]. In patients with microscopic hematuria who are at intermediate risk for urothelial cancer and would like to forego cystoscopy, clinicians may offer certain validated urine biomarkers with a high negative predictive value for detecting bladder cancer (eg, CxBladder Resolve, CxBladder Triage, nuclear matrix protein 22 [NMP22], UroVysion, Xpert Bladder Cancer Detection) to facilitate the decision regarding utility of cystocopy. (See 'Asymptomatic patients' above.)

A more detailed discussion of urine cytology and urine biomarkers for the detection of bladder cancer is presented separately. (See "Urine biomarkers for the detection of urothelial (transitional cell) carcinoma of the bladder" and "Clinical presentation, diagnosis, and staging of bladder cancer", section on 'Urine cytology' and "Clinical presentation, diagnosis, and staging of bladder cancer", section on 'Urine-based markers'.)

SPECIAL POPULATIONS

Patients on antiplatelet or anticoagulant therapy — Hematuria in a patient on antiplatelet or anticoagulant therapy should be evaluated in the same fashion as in other patients [1]. It should not be assumed that hematuria alone can be explained by chronic treatment with these medications.

In patients who present with gross (visible) hematuria and are on anticoagulation with supratherapeutic levels (eg, international normalized ratio [INR] >3 in patients on warfarin), we would hold the anticoagulant and monitor the patient for improvement or resolution of hematuria. Even if gross hematuria resolves upon holding the anticoagulant, such patients should still be thoroughly evaluated for a cause of hematuria. If the patient has concomitant acute kidney injury at the time of presentation, a diagnosis of anticoagulant-related nephropathy should also be considered. (See "Anticoagulant-related nephropathy".)

In one report of 243 patients prospectively followed for two years, the incidence of hematuria was similar between those receiving and not receiving anticoagulation with warfarin [72]. Furthermore, evaluation of patients who developed hematuria revealed a urinary cause in 81 percent of cases. Infection was most common, but papillary necrosis, renal cysts, and several malignancies of the bladder were also found.

Patients with sickle cell trait/disease — Patients with sickle cell trait or sickle cell disease can develop hematuria from several causes, including urinary tract infections, renal papillary necrosis, and, less commonly, renal medullary carcinoma. Renal medullary carcinoma is a rare and aggressive form of non-clear cell renal cancer seen almost exclusively in individuals with sickle cell trait. Thus, patients with sickle cell trait who present with hematuria should be considered as high risk for urothelial malignancy and should have an upper urinary tract imaging study as part of their evaluation. There is insufficient data to guide the optimal choice of imaging modality in this population; we would obtain computed tomography (CT) of the abdomen and pelvis without and with intravenous contrast for urography (CTU), unless contraindicated. (See 'Imaging studies' above.)

Patients with a family history of kidney cancer — Patients with microscopic hematuria and a known family history of renal cell carcinoma or known genetic kidney tumor syndrome (eg, hereditary papillary renal cell carcinoma, von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome) should have an upper urinary tract imaging study as part of their evaluation, regardless of their risk category. There is insufficient data to guide the optimal choice of imaging modality in this population; we would obtain CT of the abdomen and pelvis without and with intravenous CTU, unless contraindicated. (See "Hereditary kidney cancer syndromes".)

UNEXPLAINED HEMATURIA — 

If no diagnosis is apparent from the history, urinalysis, imaging examinations, or cystoscopy, then the most likely causes of persistent isolated hematuria are a mild glomerulopathy and a predisposition to stone disease, particularly in young and middle-aged patients.

●Glomerular disease – Although any glomerular disease may be associated with hematuria, most patients also have other signs such as proteinuria, dysmorphic red blood cells (RBCs), red blood cell RBC casts, or kidney function impairment. When persistent glomerular hematuria is essentially the only manifestation of glomerular disease, one of four disorders is most likely [67,69,73-77]:

•Immunoglobulin A (IgA) nephropathy

•Thin basement membrane nephropathy

•Mesangioproliferative glomerulonephritis without IgA deposits

•Alport syndrome (hereditary nephritis)

Postinfectious glomerulonephritis and exercise are other causes of isolated glomerular bleeding. The hematuria in these settings is typically transient (not persistent, as in the above disorders). (See "Exercise-induced hematuria" and "Glomerular disease: Evaluation and differential diagnosis in adults".)

●Hypercalciuria and hyperuricosuria – As many as 30 to 35 percent of children with apparently idiopathic hematuria (no proteinuria or infection, negative radiologic evaluation) have hypercalciuria, while 5 to 20 percent of children with recurrent hematuria have hyperuricosuria [78-80]; both disorders are often associated with a positive family history (as high as 40 to 75 percent) of stone disease [78,80]. These children are at increased risk for the future development of kidney stones. Lowering calcium excretion with a thiazide diuretic typically leads to resolution of the hematuria among those with hypercalciuria [78]; a restricted purine diet or the administration of allopurinol commonly eliminates uricosuria and hematuria in those with hyperuricosuria. (See "Kidney stones in children: Epidemiology and risk factors", section on 'Hypercalciuria'.)

Similar findings may be present in adults. Some patients have hypercalciuria or hyperuricosuria (as detected by a 24-hour urine collection) [81,82], while others have a history suggestive of stone disease without these biochemical abnormalities (although citrate excretion was not measured in this study) [77] (see "Kidney stones in adults: Epidemiology and risk factors"). Treatment with a thiazide diuretic for hypercalciuria or allopurinol for hyperuricosuria usually leads to disappearance of the hematuria [81].

●Rare conditions – Rare causes of hematuria include hereditary hemorrhagic telangiectasis, radiation cystitis, schistosomiasis (which is not rare in endemic areas), arteriovenous malformations (AVMs) and fistulas, nutcracker syndrome, and the loin pain-hematuria syndrome. AVMs, nutcracker syndrome, and loin pain-hematuria syndrome will be briefly reviewed here; the other conditions are discussed separately. (See "Chemotherapy and radiation-related hemorrhagic cystitis in cancer patients" and "Schistosomiasis: Epidemiology and clinical manifestations".)

•Arteriovenous malformations and fistulas – An AVM or fistula of the urologic tract may be either congenital or acquired. The latter is more common and usually secondary to trauma or intervention. The primary presenting sign is gross hematuria, but high-output heart failure and hypertension also may be seen [66,83]. The latter is presumably due to activation of the renin-angiotensin system resulting from ischemia distal to the AVM [84].

Ultrasound with Doppler is the examination used to evaluate for suspected renal AVM or fistula as it allows for detection of high-flow velocity. If positive, diagnosis is confirmed by conventional fluoroscopic angiography, which can be combined with selective embolization therapy in the same setting. Coils, gelatin sponges, or liquid glues such as N-butyl-2-cyanoacrylate (NBCA) are injected usually in combination for endovascular sclerotherapy [85,86]. Surgery or nephroscopy can be performed if embolization is ineffective or the hematuria recurs [84,87].

•Nutcracker syndrome – The nutcracker syndrome refers to compression of the left renal vein between the aorta and proximal superior mesenteric artery. Nutcracker syndrome can cause both microscopic and gross hematuria, primarily in children (but also adults) in Asia [88-91]. The hematuria is usually asymptomatic but may be associated with left flank pain. Nutcracker syndrome has also been associated with orthostatic proteinuria. (See "Orthostatic (postural) proteinuria", section on 'Pathogenesis' and "Evaluation of microscopic hematuria in children", section on 'Etiology' and "Evaluation of gross hematuria in children", section on 'Asymptomatic hematuria'.)

Nutcracker syndrome is usually suspected when computed tomography (CT) or magnetic resonance imaging (MRI) shows intrarenal and perirenal varices, and early enhancement of the left gonadal vein collateral. The diagnosis is confirmed on Doppler ultrasound demonstrating left renal vein compression with elevated velocities.

For patients who require treatment because of recurrent or persistent symptoms, a variety of therapies have been used, including conservative management, stent placement in the left renal vein, transposition of the superior mesenteric artery or left renal vein, autotransplantation of the left kidney, and nephrectomy [88,90-92]. In a 2007 review of 20 patients who required intervention, stenting (which has the advantage of minimal invasiveness) was performed in 15, and transposition of the superior mesenteric artery or left renal vein was performed in five [88,93,94].

•Loin-pain hematuria syndrome – The loin pain-hematuria syndrome is a poorly defined disorder characterized by loin or flank pain that is often severe and unrelenting as well as hematuria with dysmorphic RBC features suggesting a glomerular origin. Affected patients usually have normal kidney function. This disorder is discussed elsewhere. (See "Loin pain-hematuria syndrome".)

FOLLOW-UP AFTER INITIAL NEGATIVE EVALUATION — 

A cause for hematuria is often not identified. In patients with a negative evaluation for hematuria, the necessity for repeat testing (eg, urinalysis, imaging, and/or cystoscopy) largely depends upon whether hematuria was transient or persistent and upon the patient's risk for malignancy.

Follow-up of transient hematuria — In patients with transient hematuria, the approach to follow-up depends upon the patient’s risk of malignancy (algorithm 2):

●In patients who are at high risk for malignancy, we advise close follow-up and monitor with annual urinalyses. After two consecutive negative urinalyses, this follow-up may be discontinued. However, if gross hematuria occurs at any time after the initial evaluation, full evaluation should be repeated.

●In patients who are not at high risk for malignancy, we typically discontinue further evaluation for hematuria. After five years, it is reasonable to engage in shared decision making with the patient regarding a repeat evaluation for hematuria based on the patient’s risk factors at that time.

If hypertension, proteinuria, an increase in serum creatinine, or evidence of glomerular bleeding develops in a patient who has been evaluated for hematuria, the patient should be reevaluated for kidney disease. (See 'Glomerular versus nonglomerular hematuria' above.)

Follow-up of persistent hematuria — In patients who have an initial negative evaluation for persistent hematuria, we engage in shared decision making about whether to repeat a urinalysis in the future. The diagnostic utility of a repeat evaluation is low in patients who have had a negative evaluation for persistent hematuria and do not have a change in symptoms. If the patient chooses to have a repeat urinalysis, we repeat the test within 12 months.

●If the repeat urinalysis is negative for microscopic hematuria, we discontinue further evaluation for hematuria.

●If the repeat urinalysis is positive for microscopic hematuria, we engage in shared decision making regarding the need for additional evaluation. One reasonable approach is to obtain annual urinalyses in low/negligible-risk patients, while medium- and high-risk patients may need closer follow-up with more frequent urinalyses. If repeat urinalysis in a medium- or high-risk patient is positive, it may be reasonable to repeat the full evaluation.

●If, at any time after the initial evaluation, the patient develops gross hematuria, a significant increase in the degree of microscopic hematuria, or new urologic symptoms, we repeat a full evaluation for hematuria.

Our approach is largely consistent with the 2025 American Urological Association (AUA) guidelines for microscopic hematuria [1].

Potentially, the most serious disorder in the patient with unexplained persistent hematuria is the presence of an undiagnosed carcinoma of the urinary tract. The combination of a negative computed tomography (CT) of the abdomen and pelvis without and with contrast for urography (CTU), negative cytology, and negative cystoscopy is usually sufficient to exclude malignancy in the urinary tract [22]. However, the cause will subsequently become evident in some patients with careful follow-up. In a series of 421 patients with unexplained, asymptomatic microscopic hematuria who were followed at six-month intervals for more than one year, approximately 5 percent had an identifiable cause for hematuria within three years, and approximately 1 percent had a detectable urinary tract malignancy [22]. (See "Epidemiology and risk factors of urothelial carcinoma of the bladder" and "Epidemiology, pathology, and pathogenesis of renal cell carcinoma".)

SCREENING FOR HEMATURIA — 

Population- or office-based screening for hematuria in patients who have no symptoms suggestive of urinary tract disease and who have no known risk factors for urothelial malignancies or hereditable glomerular disease is not recommended. The most plausible argument for screening would be for the early detection and treatment of cancers of the kidney, collecting system, or bladder in older adults. However, these and other diseases causing hematuria do not meet basic criteria for screening: The prevalence of undetected, asymptomatic, early disease is relatively low (<2 percent); there is little evidence that hematuria is a sensitive test for localized disease; and there is little evidence in patients with renal cancer that early treatment of local disease results in a better prognosis [95].

Thus, expert groups such as the US Preventive Services Task Force (USPSTF) on the periodic health examination do not recommend screening for hematuria. (See "Screening for bladder cancer", section on 'Recommendations of expert groups'.)

SUMMARY AND RECOMMENDATIONS

●Definitions – Hematuria is defined as the presence of blood in the urine. Gross (visible) hematuria refers to hematuria that is visible to the naked eye. Microscopic hematuria refers to hematuria that is detected only by examination of the urine sediment by microscopy (picture 1). Microscopic hematuria is commonly defined as the presence of ≥3 red blood cells (RBCs) per high-power field in a centrifuged fresh urine sediment. (See 'Definitions' above.)

●General principles

•Detection – The urine dipstick test for blood (heme) is a highly sensitive test for the detection of hematuria. A positive dipstick test of 1+ of greater is considered to be significant hematuria. A positive dipstick should always be confirmed by microscopic examination of the urinary sediment. (See 'Detection of hematuria' above.)

•Confirmation – There is no consensus on how many urinalyses are needed to confirm the presence of microscopic hematuria. We repeat the urinalysis at least once for confirmation.

Red to brown colored urine can be caused by a variety of conditions other than hematuria. Thus, the initial step in the evaluation of red to brown urine is to confirm that the discoloration is due to blood or another substance (algorithm 1). (See 'Confirming true hematuria' above.)

•Glomerular versus nonglomerular hematuria - Distinguishing between glomerular and other sources of hematuria is important in guiding the evaluation of hematuria. Findings suggestive of glomerular hematuria include the presence of RBC casts and/or dysmorphic RBCs in the urine, proteinuria, and impaired kidney function. (See 'Glomerular versus nonglomerular hematuria' above.)

•Transient hematuria – Transient microscopic hematuria is a common problem in adults. Menses, vigorous exercise, trauma, and recent instrumentation (eg, urinary catheterization) are potential causes. (See 'Transient hematuria' above.)

●Causes – Hematuria may be a symptom of an underlying disease, some of which are life threatening and some of which are treatable (figure 1). The causes vary with age, with the most common being inflammation or infection of the bladder, stones, and, in older patients, a kidney or urinary tract malignancy or benign prostatic hyperplasia (BPH) (figure 2). (See 'Causes of hematuria' above.)

●Initial evaluation – The initial evaluation of patients with confirmed hematuria includes a targeted history, physical examination, and laboratory testing to identify potential causes and risk factors for hematuria and to determine whether further evaluation and referral to a specialist (nephrology or urology) are warranted. (See 'Initial evaluation' above.)

●When to refer to the emergency department – Most causes of hematuria in adults do not require urgent, time-sensitive evaluation. However, the following patients should be referred to the emergency department for more immediate evaluation and management (see 'When to refer to the emergency department' above):

•Patients with gross (visible) hematuria and visible blood clots who are experiencing symptoms of urinary tract obstruction or urinary retention (eg, anuria, lower abdominal pain).

•Patients with gross hematuria and symptoms and signs of clinically significant anemia, including tachycardia, pallor, hypotension, orthostasis, dyspnea, chest pain, and lightheadedness.

•Patients with gross (visible) hematuria and severe flank or abdominal pain, as they may have obstructive nephrolithiasis.

●Diagnostic approach based on initial evaluation – Subsequent evaluation of the patient is guided by the clinical presentation (gross versus microscopic hematuria) and the findings of the initial evaluation (algorithm 3 and algorithm 2). (See 'Gross (visible) hematuria' above and 'Microscopic hematuria' above.)

●Follow-up – A cause for hematuria is often not identified. Patients who have a negative evaluation for hematuria generally require follow-up with urinalysis, blood pressure monitoring, and, in some cases, repeat imaging and cystoscopy. The necessity for repeat imaging and cystoscopy largely depends upon whether hematuria was transient or persistent and upon the patient's risk for malignancy. (See 'Follow-up after initial negative evaluation' above.)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Chi-yuan Hsu, MD, MSc, Kerry C Cho, MD, Michael Kurtz, MD, and Adam S Feldman, MD, MPH, who contributed to an earlier version of this topic review.