1. 1
    Current Diagnosis

    • Hematuria is defined as the presence of red blood cells in the urine. Hematuria can be gross (readily visible) or microscopic (detected by dipstick or microscopy). In the adult population, any unexplained hematuria should be presumed to be of malignant origin until proven otherwise. Urologic evaluation of the upper and lower urinary tract is compulsory for patients with gross hematuria. Patients with asymptomatic microscopic hematuria (> 3 rbc/hpf) should undergo urologic evaluation once benign causes have been ruled out. The urologic evaluation includes urine analysis, serum creatinine, cystoscopy, and multiphasic computed tomography. Concurrent nephrologic evaluation should occur in select cases.

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  2. 2

    Hematuria is a common clinical finding in adults. The prevalence of hematuria ranges from 0.2% to 16%. Prevalence varies based on age, gender, frequency of testing, threshold used to define hematuria, and study group characteristics (Davis et al., 2012). Transient microscopic hematuria may occur in up to 40% of patients; however, persistent microscopic hematuria in greater than three evaluated urine samples is limited to 2% of the population (Masahito, 2010). A wide range of causes can result in hematuria. Transient hematuria may be caused by vigorous exercise, sexual intercourse, mild trauma, menstrual contamination, and instrumentation. Patients with underlying urinary tract disease can have transient or persistent hematuria. The difference between gross and microscopic hematuria is that the chances of finding significant pathology are higher in patients with gross hematuria. For example, approximately 5% of patient with microscopic hematuria in contrast to 40% of patient with gross hematuria are found to have urologic malignancy on evaluation (Khadra et al., 2000). The most common cause of gross hematuria in adults older than age 50 is bladder cancer (Gerber and Brendler, 2011).


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  3. 3
    Risk Factors

    Given the wide range of etiologies for hematuria, the risk factors are dependent on the etiology itself. The most concerning etiology of hematuria is urothelial malignancy. Smoking is the best-established and the most significant risk factor for the development of urothelial malignancies of the kidney, ureter, and bladder.


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  4. 4

    The presence of blood in the urine can be separated into glomerular and nonglomerular origin. Normal urine contains less than three red blood cells per high power field. The kidney does not excrete red blood cells under physiologic conditions. Therefore, presence of blood in the urine is due to pathology at the glomerulus (glomerular hematuria), allowing excretion of red blood cells into the urine or pathology in the urinary tract distal to the glomerulus (nonglomerular hematuria), which results in blood mixing into the already excreted urine. Nonglomerular hematuria can be further divided into medical and surgical disorders. Except for renal tumors, nonglomerular hematuria of medical/renal origin is due to tubulointerstitial, renovascular, or systemic disorders. Surgical nonglomerular hematuria or essential hematuria includes urologic tumors, stones, and urinary tract infections (Gerber and Brendler, 2011).

    The urine dipstick commonly used for the detection of blood in the urine is dependent on the peroxidase-like activity of hemoglobin, which catalyzes the reaction and causes oxidation of the chromogen indicator. False positives can occur in states of hemoglobinuria and myoglobinuria, and microscopic examination of the urine for red blood cells can distinguish hematuria. Glomerular hematuria is suggested when dysmorphic erythrocytes, red blood cell casts, and proteinuria are present. Nonglomerular hematuria can be distinguished from glomerular hematuria in the presence of circular erythrocytes and the absence of erythrocyte casts. In the surgical and medical subcategories of nonglomerular hematuria, surgical hematuria is suggested by the absence of significant proteinuria.

    Anticoagulation at normal therapeutic levels does not predispose patients to hematuria. Therefore, patients who have hematuria while receiving anticoagulation therapy should undergo evaluation similarly to patients who are not receiving anticoagulation therapy. In fact, super therapeutic anticoagulation may serve to unmask underlying pathology.


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  5. 5

    Hematuria can be caused by a spectrum of causes. Prevention can be achieved by the prevention of what results in the pathologic state. For example, smoking is a modifiable risk factor in urothelial malignancy. Patients who have never smoked are at low risk for bladder cancer.

    Smoking cessation can also reduce the risk of developing bladder cancer. Liberal fluid intake and balanced sodium and protein intake can help prevent urolithiasis. Urinary tract infections can also be prevented by good voiding habits, facilitation of complete bladder emptying, and use of vaginal estrogen cream1 in postmenopausal women.

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  6. 6
    Clinical Manifestations

    The presentation of hematuria is often dependent on the cause. Certain characteristics of the presentation can help in the investigation. Is the hematuria gross or microscopic? Is the hematuria associated with pain? Are there any irritative voiding symptoms? Is there a presence of blood clots? Is it related to exercise? Is there any family history? Is there a presence of rash, arthritis, hemoptysis, upper respiratory infection, skin infection? Is there a history of radiation, diabetes, analgesic abuse? Is there a history of smoking or occupational exposures? Table 1 highlights findings in etiologies of hematuria. Patients with bladder cancer generally present with gross painless hematuria.

    Table 1

    Differential Diagnosis and Findings in Etiologies of Hematuria

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  7. 7

    The diagnosis and evaluation of hematuria starts with a careful history, physical examination, and microscopic urine analysis. The cause in an adult patient is urologic malignancy until proven otherwise. Some important questions are outlined in the clinical manifestation section. The physical examination should focus on blood pressure, a cardiovascular examination, an abdominal examination, a palpable mass, costovertebral angle tenderness, and a complete genitourinary examination inclusive of a prostate examination in the male and vaginal examination in the female patient. The assessment should help rule out causes such as infection, menstruation, vigorous exercise, medical renal disease, viral illness, trauma, or recent urologic procedures.

    The urine should be collected as a midstream sample, and patients should be instructed to discard the initial 10 mL. The sample should be collected in a sterile cup after gently cleaning the urethral meatus with a sterilization towelette. Uncircumcised men should retract the foreskin before collection. Female patients should be asked to spread the labia adequately to allow cleansing of the urethral meatus and avoid introital contamination. The following patients may require catheterization for collection: menstruating women, obese patients, patient with a nonintact urinary tract, and patients who do intermittent catheterization or have an indwelling urinary catheter (Davis et al., 2012). A urine dipstick can be performed in the office setting, but all samples should be sent for microscopic analysis. As mentioned previously, attention should be paid to dysmorphic erythrocytes, red blood cell casts, and the presence of protein. A urine culture should be performed based on the clinical presentation and findings of urine analysis. Urine cytology does need to be performed as part of the standard workup. The laboratory workup should include an evaluation of the serum creatinine (Davis et al., 2012).

    Additional helpful tests are serum electrolytes and a complete blood count.

    Patients with a urinary tract infection should be treated appropriately and should have a urine analysis repeated in 2 to 6 weeks after treatment. Patients with an identified etiology such as urolithiasis should have a reevaluation of urine after the stone has been passed or treated.

    A urologic evaluation of the upper and lower urinary tract is compulsory for patients with gross hematuria. Patients with asymptomatic microscopic hematuria (> 3 rbc/hpf) should undergo urologic evaluation once benign causes have been ruled out. The urologic evaluation is especially important for patients with high risk factors for urothelial malignancy, such as age > 35, irritative voiding symptoms, chemical exposures, smoking history, or history of urologic disorder or malignancy. Urologic evaluation should include a cystoscopy to evaluate the urethra and bladder. Multiphasic computed tomography with and without intravenous contrast should be performed to evaluate the upper tracts. Sufficient imaging phases should be performed. Ideally, a three-phase study including a noncontrast phase (e.g., stone disease), arterial phase (e.g., renal masses), and excretory phase (e.g., ureteral masses) should be performed (Sudakoff et al., 2008). The urologist can determine the appropriate study if contrasted CT cannot be performed because of allergy or renal insufficiency. Concurrent nephrologic evaluation should occur for patients who are suspected to have glomerular causes, and the evaluation may include further serum testing and renal biopsy (Davis et al., 2012).

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  8. 8
    Differential Diagnosis

    The differential diagnosis of hematuria includes glomerular diseases, nonglomerular medical diseases, and nonglomerular surgical diseases. Table 1 shows a differential diagnosis for hematuria.

    Hematuria is considered to be from a malignant source until proven otherwise.


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  9. 9
    Therapy, Monitoring, and Complications

    Therapy, monitoring, and complications for hematuria are dependent on the etiology. It is important that hematuria not be ignored even when treated empirically. For example, it is important to recheck a urine analysis after a course of antibiotics for a presumed urinary tract infection. Often, the transient nature of hematuria fools clinicians into thinking that an intervention or observation without the appropriate workup is adequate. Unfortunately, this can result in significant morbidity from the progression of disease, especially in the case of urothelial malignancies.

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  10. 10

    Davis R., Jones S.J., Barocas D., et al. Diagnosis, evaluation and follow-up of asymptomatic microscopic hematuria (AMH) in adults. AUA guideline. J Urol. 2012;188(Suppl 6):2473.

    Gerber G.S., Brendler C.B. Evaluation of the urologic patient: History, physical, and urinalysis. In: Wein Campbell-Walsh Urology. ed 10th Philadelphia: Saunders; 2011:73–98.

    Khadra M.H., Pickard R.S., Charlton M., et al. A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol. 2000;163:524.

    Masahito J. Evaluation and management of hematuria. Prim Care. 2010;37:461.

    Sudakoff G.S., Dunn D.P., Guralnick M.L., et al. Multidetector computerized tomography urography as the primary imaging modality for detecting urinary tract neoplasms in patients with asymptomatic hematuria. J Urol. 2008;179:862.

    1  Not FDA approved for this  indication.

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