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.

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.

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>

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. 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.

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.

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

Hematuria is defined as the presence of red blood cells (RBCs) 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) in the absence of an obvious benign cause (e.g. mild trauma or sexual activity preceding the collection).

Hematuria is defined as the presence of blood in the urine. Gross hematuria and microscopic hematuria( MH) are 2 types of hematuria .^[1] Definitions for MH vary considerably and range between 1 to 10 red blood cells per high-power microscope field. ^[2] This difference is due to factors affecting related to sample collection and quantification. One of the most widely used definitions of MH 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).^[3][4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

There is limited information about the historical perspective of hematuria.

There is limited information about the historical perspective of hematuria.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [2]

Hematuria may be classified according to its source into 3 groups: extrarenal hematuria, nonglomerular renal hematuria, and glomerular hematuria. Hematuria may be classified according to the visibility of hematuria into 5 groups: Visible hematuria, initial hematuria, terminal hematuria, complete hematuria, and non-visible hematuria. Hematuria may be classified according to the duration into 2 groups: transient hematuria, and persistent or significant hematuria. Hematuria may also be classified according to the pathophysiology.

Hematuria may be classified according to its source into 3 groups: extrarenal hematuria, nonglomerular renal hematuria, and glomerular hematuria.^[1]

• Extrarenal hematuria:: More than 60% of cases of hematuria occur from a source outside the kidney.The most common nonmalignant causes of hematuria outside the kidney are infections such as cystitis , prostatitis , and urethritis .
• Nonglomerular renal hematuria: Renal stones and pyelonephritis will present with episodic pain and pyelonephritis with fever. Polycystic kidney disease (PKD) will usually present with recurring gross hematuria. ^[2]Although the degree of proteinuria correlates with the severity and progression of renal disease, microscopic hematuria does not have such correlation.
• Glomerular hematuria: IgA nephropathy is the most common cause of isolated glomerular microscopic hematuria (without significant proteinuria). It is usually asymptomatic and often is diagnosed as an incidental finding.

Hematuria may be classified according to the visibility of hematuria into 5 groups: Visible hematuria, initial hematuria, terminal hematuria, complete hematuria, and non-visible hematuria.

• Visible hematuria: Also known as Frank hematuria/ Macroscopic hematuria/ Gross hematuria.^[3] Visible hematuria can be visualized and is also known as frank, gross or macroscopic hematuria.
• Initial hematuria: May indicate urethral pathology
• Terminal hematuria: Hematuria at the end of the stream that comes from the proximal urethra (bladder neck/prostate).
• Complete hematuria: Hematuria throughout the entire stream suggests bladder, ureteric or renal pathology.
• Non-visible hematuria: Non-visible hematuria encompasses dipstick and microscopic hematuria.^[4]

Hematuria may be classified according to the duration into 2 groups: transient hematuria, and persistent or significant hematuria.

• Transient hematuria: A single urinalysis with hematuria is common and can result from menstruation, viral illness, allergy, exercise, fever, or mild trauma.
• Persistent or Significant hematuria: >3 RBCs/HPF on three urinalyses, a single urinalysis with >100 RBCs, or gross hematuria.

Hematuria may be classified according to the pathophysiology.^[5]

• Common causes of microscopic hematuria may be classified broadly according to the underlying etiology as glomerular and non glomerular, as follows:

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

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. The pathophysiology of non-glomerular hematuria might be depending on the underlying etiology. It is thought that non-glomerular hematuria is caused by either polycystic kidney disease, sickle cell disease and papillary necrosis, nephrolithiasis, trauma, leukemia, tumors, strenuous exercise, or infection. The pathophysiology of non-renal hematuria might be depending on the underlying etiology. It is thought that non-renal hematuria is the result of either stone, infection, tumor, trauma, urinary tract infection (UTI), irritation, or foreign body which might be originating from either the ureter, bladder, or urethra. It may also be caused by prostatic bleeding, vaginal bleeding, and endometriosis.

• It is understood that glomerular hematuria is caused by either the dysfunction or damage of the glomerular filtration barrier(GFB).^[1]
  • Major components of GFB include:
    • Endothelial surface layer (composed of glycosaminoglycans)
    • Endothelial cells
    • Glomerular basement membrane (GBM)
    • Slit diaphragms
    • Subpodocyte space
• The pathophysiologic mechanism of glomerular hematuria might be further classified into 6 subtype depending on the primary and histopathologic localization.^[1]
  • Injuries of the glomerular endothelial cell and surface layer
  • Primary and secondary GBM disorders
  • Diseases that can cause mesangial deposition
  • Diseases that can cause subendothelial and subepithelial deposition
  • Podocyte-associated disorders
  • Miscellaneous
• The pathophysiology of non-glomerular hematuria might be depending on the underlying etiology. It is thought that non-glomerular hematuria is caused by either polycystic kidney disease, sickle cell disease and papillary necrosis, nephrolithiasis, trauma, leukemia, tumors, strenuous exercise, or infection.^[2]
• The pathophysiology of non-renal hematuria might be depending on the underlying etiology. It is thought that non-renal hematuria is the result of either stone, infection, tumor, trauma, urinary tract infection (UTI), irritation, or foreign body which might be originating from either the ureter, bladder, or urethra. It may also be caused by prostatic bleeding, vaginal bleeding, and endometriosis.^[2]

Molecular defects involved in the pathogenesis of non-glomerular hematuria include:

• In the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD):^[3]
  • PKD1 and PKD2 genes
• In the pathogenesis of autosomal recessive polycystic kidney disease (ARPDK):^[4]
  • PKHD1 gene

Molecular defects involved in the pathogenesis of glomerular hematuria include:^[1]

• In the pathogenesis of alport syndrome:
  • COL4A5 (X linked)
  • COL4A3/COL4A4 (autosomal recessive)
• In the pathogenesis of thin basement membrane disease:
  • COL4A3/COL4A4
• In the pathogenesis of hereditary angiopathy, nephropathy, aneurysms, and muscle cramps syndrome:
  • COL4A1

• In the pathogenesis of MYH9-related disorder:
  • Non muscle myosin IIA heavy chain

• In the pathogenesis of fibronectin glomerulonephritis:
  • Fibronectin
• In the pathogenesis of fibrillary glomerulonephritis:
  • 10-30 nm fibrils
• In the pathogenesis of fabry’s disease:
  • lysosomal storage
• In the pathogenesis of immunotactoid glomerulonephritis:
  • Fibrils that are > 30 nm

• In the pathogenesis of ANCA (antineutrophil cytoplasmic antibodies):
  • Antibodies against endothelium
• In the pathogenesis of anti-GBM:
  • Antibodies against COL4

• In the pathogenesis of C3 glomerulopathy:
  • Alternative pathway

• In the pathogenesis of IgA nephritis:
  • Galactose-deficient IgA1

Gross pathology might differ depending on the underlying etiology of hematuria.

• On gross pathology,
  • Multiple cyst formation and kidney enlargement are characteristic findings of autosomal dominant polycystic kidney disease (ADPKD)^[5]

• • Solid yellow/golden lesions (because of the cells with lipid-rich cytoplasma), internal necrosis, cystic degeneration, and hemorrhage are characteristic findings of clear cell renal cell carcinoma

Microscopic pathology might differ depending on the underlying etiology of hematuria.

• On microscopic histopathological analysis,
  • Diffuse thinning of the glomerular basement membrane (GBM) is characteristic finding of thin basal membrane disease^[6]
  • Lobular appearance with massive fibronectin deposits and the absence of immunoglobulin/complement deposition are characteristic findings of fibronectin nephropathy^[7]
  • Randomly aligned fibrillar deposits that measure 12-24 nm is characteristic finding of fibrillary nephropathy^[8][9]

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

Causes of hematuria can range from benign conditions such as urinary tract infection to serious conditions such as bladder cancer.^[1] 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.

• Intraperitoneal bladder rupture

• Ureteroarterial fistula

• Hemorrhagic cystitis

• Heart failure

• Malignant hypertension

• Shock

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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., Amandeep Singh M.D.[3], Omer Kamal, M.D.[4], Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [5] Aditya Ganti M.B.B.S. [6]

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.

Hematuria should be differentiated from other conditions which might mimic hematuria such as hemoglobinuria, myoglobinuria, porphyria, bile pigments, and alkaptonuria.^[1]

• Hematuria is usually characterized by red/rusty urine color, positive heme test, red blood cells and casts on microscopy, and normal plasma. These characteristic findings might be helpful for differentiaton of hematuria from abovementioned conditions.
• Hemoglobinuria is usually characterized by pink/red urine color, positive heme test, no cells on microscopy, and pink plasma.
• Myoglobinuria is usually characterized by rusty urine color, positive heme test, no cells on microscopy (casts might be seen), and normal plasma.
• Porphyria is usually characterized by urine color turns black/brown/red when the urine exposed to sunlight, negative heme test, normal microscopic findings, and normal plasma.
• Bile pigments is usually characterized by brown urine color, negative heme test, normal microscopic findings, and dark to bright yellow (icteric) plasma.
• Alkaptonuria is usually characterized by urine color turns black when the urine exposed to sunlight, negative heme test, normal microscopic findings, and normal plasma.

Template:WH Template:WS

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

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%.^[1] 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.^[2]

According to the American Urological Association (AUA) guidelines, the prevalence of hematuria ranging from 2100 to 31400 per 100,000 individuals.^[3]

• Microscopic hematuria is quite common, with a prevalence of approximately 6.5% of adults, varying according to the characteristics of the population.^[4] The prevalence of microscopic hematuria ranges from 1-20% depending on the population studied and also varies with on age, gender, frequency of testing, threshold used to define MH and presence of risk factors such as smoking.^[4]

Young patients are more likely to have intrinsic renal pathology (i.e. glomerulonephritis whereas malignancy is more common in the elderly).^[5]

Malignancy of the bladder and kidney is at least twice as common in males than in females. Women are more commonly affected by urinary tract infections.

Template:WH Template:WS

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

Common risk factors in the development 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.

Common risk factors in the development of hematuria include:

• Recent infection: Post-infectious glomerulonephritis, IgA nephropathy
• Exercise: Long distance runners are prone to exercise-induced urinary bleeding.
• Age: Males older than 50 years have an enlarged prostate that can cause hematuria.
• Sex: 50% of all women suffer from urinary tract infections at least once in their lifetime, which can also cause urinary bleeding.
• History of any of the following:
  • Chronic indwelling foreign body
  • Chronic urinary tract infection
  • Exposure to known carcinogenic agents or alkylating chemotherapeutic agents
  • Gross hematuria
  • Irritative voiding symptoms
  • Pelvic irradiation
  • Urologic disorder or disease

Common risk factors for urinary tract malignancy in patients with hematuria:^[1][2][3]

• Age older than 35 years
• Analgesic abuse
• Exposure to chemicals or dyes (benzenes or aromatic amines)
• Male sex
• Past or current smoking

History of any of the following:

• Chronic indwelling foreign body
• Chronic urinary tract infection
• Exposure to known carcinogenic agents or alkylating chemotherapeutic agents
• Gross hematuria
• Irritative voiding symptoms
• Pelvic irradiation
• Urologic disorder or disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

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.

There is insufficient evidence to recommend routine screening for bladder cancer in patients with hematuria.

• According to the U.S. Preventive Services Task Force (USPSTF), screening for bladder cancer in patients with hematuria is not recommended because of the insufficient evidence of benefit against harm. 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.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2] Omer Kamal, M.D.[3]

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.

Natural history of hematuria usually depends on the underlying etiology.

Complications of hematuria usually depend on the underlying etiology.

Depending on the underlying etiology of the hematuria, the prognosis may vary.^[1]

• 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.

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