Hematuria Hossein Hamidi Nephrologist Hematuria • • • Hematuria is the excretion of abnormal amounts of red blood cells (RBCs) into the urine. Normal individuals excrete about 1 million RBCs per day in their urine. When translated to the sediment of a spun urine specimen, this equates to about 1 to 3 RBCs per high-power field (HPF). Therefore excretion of more than 3 RBCs per HPF is abnormal and may warrant further evaluation. Asymptomatic “microscopic hematuria” is very common ; it may be detected in up to 13% of adults. Routine screening of healthy individuals for the presence of hematuria is not recommended by the U.S. Preventive Services Task Force. Hematuria • • • • Gross hematuria may first be detected by a change in urine color. Microscopic hematuria can be detected by dipstick methods, microscopic examination, or both. Dipstick methods may be applied as diagnostic tests in patients with known kidney disease or as screening tools in healthy or high-risk individuals. The U.S. Preventive Services Task no longer recommends screening for occult hematuria in the general population. Even when the urine is red, or when a dipstick screening test result is positive, the sediment should be examined to deter mine whether red cells are present. The presence of other pigments such as free hemoglobin and myoglobin can masquerade as hematuria. • • • When such testing reveals hematuria, the person’s age, gender, race, medical history, and physical findings should be considered in deciding whether to further evaluate this finding and, if so, in determining the most appropriate diagnostic studies and the sequence in which they should be performed. Asymptomatic microscopic hematuria should be confirmed in at least two of three midstream clean - catch voiding's. If microscopic hematuria spontaneously resolves, evaluation decisions are strongly influenced by the clinician’s index of suspicion. • • • • • Gross hematuria, especially if clots are passed, usually indicates a urologic source of bleeding. Even a single episode of gross hematuria mandates evaluation. The most common cause of gross hematuria in young women (<40 years of age) is urinary tract infection (UTI). Malignancy must be strongly considered and ruled out by appropriate studies in older patients. Brown, “Coca-Cola”–colored, or smoky urine with RBCs present on micros-copy is very suggestive of a glomerular source of bleeding. History and Review of Systems • • • • Three major factors influencing the workup are the patient’s gender, race, and age. The common causes of hematuria in children and young adults are much different than those in older individuals. Hematuria in adults older than 40 years (some experts propose an age cutoff of older than 50 years) must be considered a sign of malignancy. Hypercalciuria , and less commonly hyperuricosuria, cause hematuria frequently in children but less commonly in adults. Hematuria due to UTI is much more common in women , whereas older men may bleed from the prostate. History and Review of Systems • • • The combination of hematuria with fever, dysuria, or flank pain, or a prior history of these symptoms raises the likelihood of infection, stones, or malignancy. When a patient with hematuria has family members with renal failure, polycystic kidney disease or Alport ’s disease should be considered. Familial hearing loss, especially in male relatives, also suggests Alport’s disease. A very common cause of otherwise unexplained asymptomatic familial hematuria is thin basement membrane disease. Hematuria sometimes occurs after vigorous exercise or participation in contact or noncontact sports . History and Review of Systems • • • Travel history may be very important as, for example, when hematuria develops in patients who have traveled to areas where Schistosoma haematobium infection or tuberculosis is endemic. Bleeding disorders and anticoagulants will cause any pathologic GU structures such as malignancies to bleed more readily. This is especially common in older patients. A history of cigarette smoking (or second-hand smoke exposure) increases the risk of bladder cancer twofold to four fold. History and Review of Systems • • Occupational exposure to aniline dyes and aromatic amines and amides; treatment with some chemotherapeutic agents such as cyclophosphamide and mitotane; and radiation to the pelvis increase the risk for uroepithelial cancers. A recent history of pharyngitisfol lowed by hematuria raises the possibility of glomerulonephritis with synpharyngitic bleeding. Chronic glomerulonephritis, most commonly immunoglobulin A (IgA) nephropathy, is often exacerbated by an upper respiratory tract infection and may result in gross hematuria. This is distinct from post streptococcal glomerulonephritis, which occurs 2 to 6 weeks following the infection. History and Review of Systems • • With gross hematuria, a history of initiation hematuria suggests a urethral source, whereas termination hematuria is suggestive of bladder neck or prostatic urethra pathology. Blood clots in some the urine usually denote structural urologic pathology. Physical Examination • • • • • Evaluation of blood pressure and volume status is especially important when glomerulonephritis is a consideration. If palpation of the abdomen reveals a mass, a renal tumor or hydronephrosis may exist. A palpable bladder after voiding indicates obstruction or retention. Atrial fibrillation raises the possibility of renal embolic infarction, especially if the patient has flank pain. Costovertebral angle tenderness is also suggestive of pyelonephritis, nephrolithiasis, or ureteropelvic junction obstruction. Physical Examination • • A bruit over the kidney suggests a vascular cause. Careful genital and rectal examination is necessary to diagnose prostatitis, prostate cancer, epididymitis, meatal stenosis, and other structural causes of hematuria . Laboratory Tests • A diagnosis of gross hematuria is suggested by red or brown urine. Only about 1 mL of blood causes 1 L of urine to become red. However, many substances other than RBCs can produce. red or brown urine. Many chemicals, medications, and food metabolites can produce a spectrum of urine colors. Laboratory Tests Laboratory Tests • • • • A chemical test for hemoglobin is very helpful in distinguishing among these possibilities. The most commonly used method of testing the urine for blood is the urine test strip or dipstick, which utilizes the peroxidase-like activity of hemoglobin to generate a color change. The test strip does not react with most nonhemoglobin pigments that can color the urine. In addition to detecting the hemoglobin within RBCs, however, the test reaction yields a positive result with free hemoglobin and myoglobin. Laboratory Tests • It is crucial to separate hematuria caused by glomerular abnormalities from bleeding due to other pathologic kidney conditions (tumors or cysts) or pathologic processes distal to the glomerulus (interstitial disease, stones, or tumors, or other processes affecting the renal pelvis, ureters, bladder, urethra, prostate, or other lower GU system structures). When blood originates from glomeruli, the RBCs pass through the length of the renal tubules, where they are subjected to marked changes in osmolality, ionic strength, pH, and other forces. Compression of the RBCs together with urine proteins creates RBC casts and identification of these casts on microscopic examination is excellent evidence of glomerular bleeding. Although quite specific, RBC casts often are not seen even with definite glomerular bleeding. Laboratory Tests Laboratory Tests • • A more common helpful finding in glomerular bleeding is the identification of dysmorphic RBCs of varying shape and sizes with blebs, budding, and especially the vesicle-shaped protrusions that characterize acanthocytes. For dysmorphic RBCs to be an excellent indicator of glomerular bleeding, most of the urine RBCs should be affected. Acanthocytes are quite specific, however, and if they represent more than 5% of the RBCs, this is very a suggestive sign of glomerular bleeding. Laboratory Tests Laboratory Tests • • Another indication that bleeding is more likely of glomerular origin is coexistent significant proteinuria (>0.5 g/day or >0.5 g protein per gram of creatinine). The presence of pyuria with hematuria suggests inflammation or infection and warrants a urine culture. Urine cytologic analysis is indicated when otherwise unexplained hematuria is documented. It has good specificity when results are positive and a sensitivity of about 80% for bladder cancer but a much lower sensitivity for upper tract malignancy. Imaging • • When hematuria is not believed to be of glomerular origin, then computed tomography (CT) with and without intravenous (IV ) contrast is currently the preferred initial imaging modality to evaluate microscopic and gross hematuria and has largely replaced intravenous pyelography (IVP). CT urography has excellent sensitivity for stones, identifies most kidney tumors, and reveals other non–GU tract abdominal pathologic processes. The major downside of a CT scan is the need for IV contrast and the significant radiation exposure. Imaging • If CT cannot be done, then renal ultrasonography is the next best initial imaging test. If the explanation for hematuria is not evident on the initial study, the next diagnostic imaging test to perform is cystoscopy.