Hematuria overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2] Steven C. Campbell, M.D., Ph.D. Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [3] Aida Javanbakht, M.D.

Overview

Hematuria is defined as the presence of blood in the urine. Gross hematuria and microscopic hematuria( MH) are 2 types of hematuria. One of the most widely used definitions of microhematuria is the presence of at least two or three red blood cells per high power-field on a properly collected urinary specimen (confirmation should be done with 2 or 3 urinalyses taken consecutively) in the absence of an obvious benign cause (e.g. mild trauma or sexual activity preceding the collection). Urinary dipstick it lacks specificity for MH as it also detects myoglobin and free heme without the presence of any hematuria. Hematuria may be classified based on its source, visibility, duration, and pathophysiology. The pathophysiology of hematuria depends on the underlying etiology. It is understood that glomerular hematuria is caused by either the dysfunction or damage of the glomerular filtration barrier(GFB). Molecular defects (COL4A5, COL4A3/COL4A4, COL4A1, Non muscle myosin IIA heavy chain, Fibronectin, etc.) might be involved in the pathogenesis of glomerular hematuria. Gross pathology and microscopic pathology might differ depending on the underlying etiology of hematuria. Causes of hematuria can range from benign conditions such as urinary tract infection to serious conditions such as bladder cancer. The extrarenal site is responsible for more than 60% of cases of hematuria. Of these, the most important underlying disease is malignancy. In the primary care population, about 5% of patients with microscopic hematuria will have a urinary tract malignancy, mainly of the bladder or prostate. The most common nonmalignant causes of extrarenal hematuria are infections, such as cystitis, prostatitis, and urethritis.Regarding renal causes of microscopic hematuria, the most common cause of isolated glomerular hematuria (without significant proteinuria) is IgA nephropathy, followed by thin basement membrane disease, hereditary nephritis (Alport syndrome), and mild focal glomerulonephritis of other causes. Resolvable or self-limited causes of hematuria include strenuous exercise, fever, medications, exposure to toxins (such as contrast dyes used in radiological procedures), physical injury to the kidney or bladder, menstrual or gynecological bleeding. Gross hematuria(GH) must be distinguished from pigmenturia, which may be due to endogenous sources (e.g., bilirubin, myoglobin,and porphyrins), foods ingested (e.g., beets and rhubarb), drugs (e.g., phenazopyridine), and simple dehydration. This distinction can be made easily by urinalysis with microscopy. Notably, myoglobinuria and other factors can cause false-positive chemical tests for hemoglobin, so urine microscopy is required to confirm the diagnosis of hematuria. GH also must be distinguished from vaginal bleeding in women, which usually can be achieved by obtaining a careful menstrual history, collecting the specimen when the patient is not having menstrual or gynecologic bleeding, or, if necessary, obtaining a catheterized specimen. GH may also be detected by the presence of blood spotting on the undergarments of incontinent patients. After ruling out vaginal bleeding and mimics of hematuria, a urologic source must be suspected. According to the American Urological Association (AUA) guidelines, the prevalence of hematuria ranging from 2100 to 31400 per 100,000 individuals. Asymptomatic hematuria is common in clinical practice, with a prevalence ranging from 0.18% to 38.7%. Transient microscopic hematuria may occur in 6% to 39% of the population studied, but persistent microscopic hematuria in 3 or more consecutive urinalyses occurs less often, and is seen in 0.5% to 2% of the population under study. In the prevalence of underlying urinary tract disease, there is no clear difference between patients with transient microscopic hematuria and those with persistent microscopic hematuria. According to the American Urological Association (AUA) guidelines, the prevalence of hematuria ranging from 2100 to 31400 per 100,000 individuals. Asymptomatic hematuria is common in clinical practice, with a prevalence ranging from 0.18% to 38.7%. Transient microscopic hematuria may occur in 6% to 39% of the population studied, but persistent microscopic hematuria in 3 or more consecutive urinalyses occurs less often, and is seen in 0.5% to 2% of the population under study. In the prevalence of underlying urinary tract disease, there is no clear difference between patients with transient microscopic hematuria and those with persistent microscopic hematuria. Certain factors that increase the chance of hematuria include recent infection, strenuous exercise or normal exercise under extreme circumstances, males > 50 years old, and female sex (due to the higher prevalence of urinary tract infection). Common risk factors for urinary tract malignancy in patients with hematuria include age >35, analgesic abuse, exposure to chemicals or dyes (benzenes or aromatic amines), male sex, and smoking history. There is insufficient evidence to recommend routine screening for bladder cancer in patients with hematuria. However, according to the recently developed scoring system known as Haematuria Cancer Risk Score (HCRS), screening for bladder cancer in patients with hematuria with high HCRS score (based on age, sex, smoking history, and type of hematuria) might be recommended. Natural history, complications, and prognosis of hematuria usually depend on the underlying etiology. Accompanying proteinuria might indicate significant kidney disease. The presence of proteinuria, hypertension, and/or abnormal renal function might be associated with a particularly poor prognosis among patients with hematuria. Isolated hematuria is associated with a good prognosis in children. Specifically, among patients with gross hematuria, 50% have been found to have a demonstrable cause, with 20% to 25% found to have a urologic malignancy, most commonly bladder cancer and kidney cancer. Given the increased frequency with which clinically significant findings are associated with gross hematuria, the recommended evaluation in this setting is relatively uniform. That is, patients presenting with gross hematuria in the absence of antecedent trauma or culture-documented UTI should be evaluated with a urine cytologic examination, cystoscopy, and upper tract imaging, preferably CT urogram.  History and symptoms of hematuria depend on the etiology. The history should also include an assessment of associated symptoms, such as gross hematuria, voiding symptoms, or flank pain. Patients' risk factors for known causes of hematuria also should be queried. It is important to know the patient's urologic history, particularly any surgeries or febrile UTIs. It is also critical to ask about the patient's general medical history, to identify potentially contributory diagnoses, such as hypertension, renal insufficiency, bleeding disorders, or sickle cell disease. Current medication use, including anticoagulants and antiplatelet therapies, should be elicited, along with recent coagulation values and any concomitant medications that would potentiate the effects of blood thinners. Family history of nephritis, polycystic kidneys, and rare familial tumor syndromes of the kidney (e.g., von Hippel-Lindau) or urothelium (e.g., Lynch syndrome) also may be informative. Physical examination of the patient with MH should be focused on isolating the underlying cause. The physical examination findings usually depend on the underlying etiology. Patients with gross hematuria must be assessed for hemodynamic stability with careful attention to vital signs, anemia with a complete blood count, and, for patients on anticoagulation, coagulation parameters to ensure that levels are within the therapeutic range. After initial stabilization, the diagnostic evaluation should then proceed, with cause-specific management. Often, the diagnosis is made on the basis of the medical history and urine and blood tests— especially in young people in whom the risk of malignancy is negligible and the symptoms are generally self-limited. Cystoscopy may be helpful in the evaluation of the lower urinary tract to rule out cancer, especially bladder cancer, in patients with gross hematuria without another explanation. Computed tomography(CT) may be helpful in the diagnosis of bladder cancer in a patient with gross hematuria without any obvious etiology. However, ultrasonography plus cystoscopy are usually enough, less costly, and safer as opposed to CT which includes the use of contrast material. Computed tomography(CT) of the kidneys and urinary tract is better than ultrasound in detecting stones in patients with hematuria, and it has the highest sensitivity, at 94% to 98%. Noncontrast helical CT is excellent for the detection of urinary stones. Magnetic Resonance Imaging (MRI) is usually not recommended for the evaluation of hematuria. Ultrasound may be helpful in the evaluation of hematuria. Ultrasound(US) offers an accurate, noninvasive approach to rule out obstructive uropathy, determine the renal size and cortical thickness, and look for masses or cysts. The availability of a color duplex to assess renal vascular flow and resistance provides additional information regarding renal parenchyma. Other imaging studies for hematuria include intravenous urography and endoscopy. A biopsy may be helpful in the diagnosis of bladder cancer. Transurethral resection of bladder tumor (TURBT) is a procedure for the resection of bladder cancer that also provides a sample for biopsy. Kidney biopsy may be helpful in the diagnosis of glomerular diseases and it might be required in the presence of dysmorphic red blood cells or red blood cell casts. The treatment of hematuria is driven by the underlying pathophysiology and the majority of patients recover with supportive therapy. Most common medicines that might be used based on the etiology include hypertension medications, corticosteroids, and immunosuppressive agents. A procedure called plasmapheresis may sometimes be used for glomerulonephritis caused by immune problems. Surgery for hematuria depends on the underlying etiology. There are no established measures for the primary prevention of hematuria. There are no established measures for the secondary prevention of hematuria.

Definition

Hematuria is defined as the presence of blood in the urine. Gross hematuria and microscopic hematuria( MH) are 2 types of hematuria. One of the most widely used definitions of microhematuria is the presence of at least two or three red blood cells per high power-field on a properly collected urinary specimen (confirmation should be done with 2 or 3 urinalyses taken consecutively) in the absence of an obvious benign cause (e.g. mild trauma or sexual activity preceding the collection). Urinary dipstick it lacks specificity for MH as it also detects myoglobin and free heme without the presence of any hematuria. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline.] J Urol 188 (6 Suppl):2473-81. DOI:10.1016/j.juro.2012.09.078 PMID: 23098784</ref>

Classification

Hematuria may be classified based on its source, visibility, duration, and pathophysiology.

classification by its source	Classification by the visibility	Classification by the duration of hematuria	Classification by Pathophysiology
Extrarenal hematuria Nonglomerular renal hematuria Glomerular hematuria	Visible hematuria Non-Visible hematuria	Transient hematuria Persistent or Significant hematuria	Glomerular hematuria Non-glomerular renal hematuria Upper urinary tract Lower urinary Tract

Pathophysiology

The pathophysiology of hematuria depends on the underlying etiology. It is understood that glomerular hematuria is caused by either the dysfunction or damage of the glomerular filtration barrier(GFB). Molecular defects (COL4A5, COL4A3/COL4A4, COL4A1, Non muscle myosin IIA heavy chain, Fibronectin, etc.) might be involved in the pathogenesis of glomerular hematuria. Gross pathology and microscopic pathology might differ depending on the underlying etiology of hematuria.

Causes

Causes of hematuria can range from benign conditions such as urinary tract infection to serious conditions such as bladder cancer. Extrarenal site is responsible for more than 60% of cases of hematuria. Of these, the most important underlying disease is malignancy. In the primary care population, about 5% of patients with microscopic hematuria will have a urinary tract malignancy, mainly of the bladder or prostate. The most common nonmalignant causes of extrarenal hematuria are infections, such as cystitis, prostatitis, and urethritis.Regarding renal causes of microscopic hematuria, the most common cause of isolated glomerular hematuria (without significant proteinuria) is IgA nephropathy, followed by thin basement membrane disease, hereditary nephritis (Alport syndrome), and mild focal glomerulonephritis of other causes. Resolvable or self-limited causes of hematuria include strenuous exercise, fever, medications, exposure to toxins (such as contrast dyes used in radiological procedures), physical injury to the kidney or bladder, menstrual or gynecological bleeding.

Differential Diagnosis

Gross hematuria(GH) must be distinguished from pigmenturia, which may be due to endogenous sources (e.g., bilirubin, myoglobin,and porphyrins), foods ingested (e.g., beets and rhubarb), drugs (e.g., phenazopyridine), and simple dehydration. This distinction can be made easily by urinalysis with microscopy. Notably, myoglobinuria and other factors can cause false-positive chemical tests for hemoglobin, so urine microscopy is required to confirm the diagnosis of hematuria. GH also must be distinguished from vaginal bleeding in women, which usually can be achieved by obtaining a careful menstrual history, collecting the specimen when the patient is not having menstrual or gynecologic bleeding, or, if necessary, obtaining a catheterized specimen. GH may also be detected by the presence of blood spotting on the undergarments of incontinent patients. After ruling out vaginal bleeding and mimics of hematuria, a urologic source must be suspected.

Epidemiology and Demographics

According to the American Urological Association (AUA) guidelines, the prevalence of hematuria ranging from 2100 to 31400 per 100,000 individuals. Asymptomatic hematuria is common in clinical practice, with a prevalence ranging from 0.18% to 38.7%. Transient microscopic hematuria may occur in 6% to 39% of the population studied, but persistent microscopic hematuria in 3 or more consecutive urinalyses occurs less often, and is seen in 0.5% to 2% of the population under study. In the prevalence of underlying urinary tract disease, there is no clear difference between patients with transient microscopic hematuria and those with persistent microscopic hematuria.

Risk Factors

Certain factors that increase the chance of hematuria include recent infection, strenuous exercise or normal exercise under extreme circumstances, males > 50 years old, and female sex (due to the higher prevalence of urinary tract infection). Common risk factors for urinary tract malignancy in patients with hematuria include age >35, analgesic abuse, exposure to chemicals or dyes (benzenes or aromatic amines), male sex, and smoking history.

Screening

There is insufficient evidence to recommend routine screening for bladder cancer in patients with hematuria. However, according to the recently developed scoring system known as Haematuria Cancer Risk Score (HCRS), screening for bladder cancer in patients with hematuria with high HCRS score (based on age, sex, smoking history, and type of hematuria) might be recommended.

Natural History, Complications and Prognosis

Natural history, complications, and prognosis of hematuria usually depend on the underlying etiology. Accompanying proteinuria might indicate significant kidney disease. The presence of proteinuria, hypertension, and/or abnormal renal function might be associated with a particularly poor prognosis among patients with hematuria. Isolated hematuria is associated with a good prognosis in children.

Diagnosis

Diagnostic Evaluation

Specifically, among patients with gross hematuria, 50% have been found to have a demonstrable cause, with 20% to 25% found to have a urologic malignancy, most commonly bladder cancer and kidney cancer. Given the increased frequency with which clinically significant findings are associated with gross hematuria, the recommended evaluation in this setting is relatively uniform. That is, patients presenting with gross hematuria in the absence of antecedent trauma or culture-documented UTI should be evaluated with a urine cytologic examination, cystoscopy, and upper tract imaging, preferably CT urogram.

History and Symptoms

History and symptoms of hematuria depend on the etiology. The history should also include an assessment of associated symptoms, such as gross hematuria, voiding symptoms, or flank pain. Patients' risk factors for known causes of hematuria also should be queried. It is important to know the patient's urologic history, particularly any surgeries or febrile UTIs. It is also critical to ask about the patient's general medical history, to identify potentially contributory diagnoses, such as hypertension, renal insufficiency, bleeding disorders, or sickle cell disease. Current medication use, including anticoagulants and antiplatelet therapies, should be elicited, along with recent coagulation values and any concomitant medications that would potentiate the effects of blood thinners. Family history of nephritis, polycystic kidneys, and rare familial tumor syndromes of the kidney (e.g., von Hippel-Lindau) or urothelium (e.g., Lynch syndrome) also may be informative.

Physical Examination

Physical examination of the patient with MH should be focused on isolating the underlying cause. The physical examination findings usually depend on the underlying etiology.

Laboratory Findings

Patients with gross hematuria must be assessed for hemodynamic stability with careful attention to vital signs, anemia with a complete blood count, and, for patients on anticoagulation, coagulation parameters to ensure that levels are within the therapeutic range. After initial stabilization, the diagnostic evaluation should then proceed, with cause-specific management. Often, the diagnosis is made on the basis of the medical history and urine and blood tests— especially in young people in whom the risk of malignancy is negligible and the symptoms are generally self-limited.

Cystoscopy

Cystoscopy may be helpful in the evaluation of the lower urinary tract to rule out cancer, especially bladder cancer, in patients with gross hematuria without another explanation.

CT

Computed tomography(CT) may be helpful in the diagnosis of bladder cancer in a patient with gross hematuria without any obvious etiology. However, ultrasonography plus cystoscopy are usually enough, less costly, and safer as opposed to CT which includes the use of contrast material. Computed tomography(CT) of the kidneys and urinary tract is better than ultrasound in detecting stones in patients with hematuria, and it has the highest sensitivity, at 94% to 98%. Noncontrast helical CT is excellent for the detection of urinary stones.

MRI

Magnetic Resonance Imaging (MRI) is usually not recommended for the evaluation of hematuria.

Ultrasound

Ultrasound may be helpful in the evaluation of hematuria. Ultrasound(US) offers an accurate, noninvasive approach to rule out obstructive uropathy, determine the renal size and cortical thickness, and look for masses or cysts. The availability of a color duplex to assess renal vascular flow and resistance provides additional information regarding renal parenchyma.

Other Imaging Findings

Other imaging studies for hematuria include intravenous urography and endoscopy.

Other Diagnostic Studies

A biopsy may be helpful in the diagnosis of bladder cancer. Transurethral resection of bladder tumor (TURBT) is a procedure for the resection of bladder cancer that also provides a sample for biopsy. Kidney biopsy may be helpful in the diagnosis of glomerular diseases and it might be required in the presence of dysmorphic red blood cells or red blood cell casts.

Treatment

Medical Therapy

The treatment of hematuria is driven by the underlying pathophysiology and the majority of patients recover with supportive therapy. Most common medicines that might be used based on the etiology include hypertension medications, corticosteroids, and immunosuppressive agents.

Interventions

A procedure called plasmapheresis may sometimes be used for glomerulonephritis caused by immune problems.

Surgery

Surgery for hematuria depends on the underlying etiology.

Primary Prevention

There are no established measures for the primary prevention of hematuria.

Secondary Prevention

There are no established measures for the secondary prevention of hematuria.