Hematuria is the medical term which means blood in the urine. Hematuria may be secondary to visible blood (gross hematuria) or blood invisible to the naked eye (microscopic hematuria). Blood in the urine may originate anywhere in the urinary tract.
Some of the more common or serious causes of hematuria are:
(1) Cancer of the lining of the urinary tract -- urothelial carcinoma (commonly known as transitional cell carcinoma) -- This is commonly associated with smoking cigarettes.
(2) Cancer of the kidneys -- renal carcinoma (commonly known as renal cell carcinoma).
(3) Urinary tract infection (UTI) -- common.
(4) Kidney stones -- stones anywhere within the urinary tract -- common.
(5) Benign kidney masses -- benign tumors.
(6) Kidney disease (medical diseases of the kidneys).
(7) Trauma/injury to the urinary tract.
(8) Blood thinners (anticoagulants) -- Coumadin/warfarin, Plavix and others -- very common.
(9) False hematuria (pseudohematuria) -- red, orange or dark colored urine (with no red blood cells in the urine) -- possible causes: beets, rhubarb, blackberries, laxatives (containing cascara or sienna), Thorazine, thioridazine, Diprivan (propofol), porphyrins, vitamin C, carrots, some squash, rifampin, Coumadin (warfarin), Pyridium (phenazopyridine), fava beans, aloe, some chemotherapy drugs, chloroquine, primaquine, Flagyl (metronidazole), Macrodantin/Macrobid (nitrofurantoin), methocarbamol …
(10) Indeterminate (uncertain) causes -- hematuria for reasons which may not be readily determined -- common, but careful follow-up and regular urology re-evaluation is always needed in such cases.
If you have directly visualized red blood or dark red blood in the urine, you have had gross hematuria. Patients with gross hematuria more commonly have serious causes for the blood in the urine.
If you have directly visualized red blood or dark red blood in the urine you have had gross hematuria and answers to the following questions are important.
(1) Was the blood seen at the beginning of the urine stream?
(2) Was the blood at the end of the urine stream?
(3) Was the blood throughout the urine stream?
(4) Did you only see blood in the toilet or on toilet tissue?
(5) If you only saw blood in the toilet or only on toilet tissue, could the blood have come from the stool rather than the urine?
(6) (For women only) If you only saw blood in the toilet or on toilet tissue, could the blood have come from the vagina (menstrual blood) rather than the urine?
(7) Was the blood in the urine found at a time when you were suspected of having a urinary tract infection/bladder infection?
(8) Was blood found at a time when you were experiencing pain?
(9) Was the blood in the urine found at a time when you were having a medical problem known to cause blood in the urine?
If you have only been found to have nonvisible blood in the urine, you have had microscopic (invisible) hematuria. Microscopic hematuria may be associated with serious medical problems in some cases. Various labs and experts disagree as to what degree of microscopic hematuria may be normal. The relative medical importance of microscopic hematuria may depend on the circumstances within which it was found. For example, some blood associated with a urinary tract infection may be less worrisome than blood found in other circumstances. Nonetheless, urinary tract infections may require further investigation (especially in men). While a miniscule amount of microscopic blood in the urine may be common, some experts suggest that even the appearance of one microscopic red blood cell in the urine deserves investigation. Others say that up to five for more red blood cells per each microscope viewing field may be considered normal. Red blood cells in the urine may be further characterized by their shape under the microscope.
Confusing? Leave it to say, the finding of microscopic hematuria deserves investigation by a urologist.
If you have been found to have invisible microscopic blood in the urine, answers to the following questions are important.
(1) Was the blood in the urine found at a time when you were suspected of having a urinary tract infection (UTI) or bladder infection?
(2) Was blood found at a time when you were experiencing pain? Yes .. No .. Unsure If so, where was the pain located?
(3) Was the blood in the urine found at a time when you were having a medical problem known to cause blood in the urine?
Evaluations for gross hematuria and microscopic hematuria are similar, but slightly different tests may be recommended for different situations. It is often recommended that patients with blood in the urine undergo x-rays of the upper urinary tracts. The upper urinary tracts include the kidneys and the drainage system of the kidneys (the ureters). There are many different types of x-rays which may be performed, as no single x-ray is perfect. All x-rays carry certain risks including risks of radiation to the patient and to unborn babies (women must always inform all healthcare providers when pregnant or possibly pregnant), risks of allergic reactions to IV contrast (inform all healthcare providers if you are allergic to iodine or allergic to IV contrast) and risks of kidney disease or kidney failure (inform all healthcare providers if you have been diagnosed with diabetes, hypertension/high blood pressure or any type of kidney disease).
Intravenous Pyelography (IVP)
A commonly recommended x-ray study is intravenous pyelography (IVP), sometimes called intravenous urography (IVU). This series of plain film x-rays of the kidneys, ureters and bladder are performed before and after the administration of intravenous contrast (dye). The test is usually performed in an outpatient radiology department of a hospital. The test is painless beyond having an IV started. The iodine based IV contrast is excreted into the urine, allowing doctors to visualize all portions of the upper urinary tracts. This study generally provides good visualization of the parts of the urinary tract containing urine. However, this study can miss small kidney masses (such as small cancers) and other small anatomical abnormalities (such as small stones). The IVP or any x-ray using IV contrast can provide functional information about the kidneys, in addition to information about the anatomy of the urinary tract.
There is a small risk of allergic reaction to IV contrast. Serious IV contrast allergies are rare but potentially life-threatening. IV contrast also poses some risk of temporary or permanent renal failure for patients prone to renal failure. Such patients may have pre-existing kidney disease, diabetes, dehydration or they may use particular medications affecting kidney function. The use of IV contrast in patients using a diabetic medication known as metformin (Glucophage, Glumetza, Fortamet, Riomet) may be associated with development of a very serious condition known as lactic acidosis. Fortunately, the development of this very serious condition is quite rare, estimated to occur in about five out of every 100,000 patients, primarily occurring in dehydrated diabetic patients with chronically poor kidney function. Ideally, metformin should be discontinued for 48 hours before and after the use of IV contrast.
Computerized Tomography (CT)
Another option for radiographic assessment of the kidneys and upper urinary tracts is CT scanning. CT scanning may be performed without the use of IV contrast, if the doctor is primarily suspects stones as the cause for blood in the urine. More than 95% of all kidney stones are well visualized by CT scanning without IV contrast. However without IV contrast, no information is gained about the function of the kidneys.
In order to identify and characterize abnormalities other than stones, IV contrast is necessary at the time of the CT. Such a CT scan may identify small masses, cancers or other abnormalities. In this case, the same IV contrast precautions are necessary as described for IVP (see above). CT scanning offers the additional benefit of being able to visualize anatomical structures outside of the urinary tract. In fact, it is not unusual to discover unexpected findings outside of the urinary tract with CT imaging. Some incidental discoveries can be life-saving. However, other incidental discoveries could lead to costly and unnecessary additional testing.
In general, noncontrast CT scanning is better for stones, contrast enhanced CT scanning (known commonly as “CT urography”) is better identifying kidney masses and IVP imaging might better identify small masses involving of the lining of the urinary tract.
Kidney ultrasound is a reasonably good radiology test that does not involve radiation at all. Sound waves are used to image body structures. The ultrasound may identify medium to large sized renal masses and cancers, or dilation of the upper urinary tracts (hydronephrosis). The advantage of the ultrasound is that it is quick and easy to perform, does not require the use of IV contrast and does not involve radiation.
Kidney ultrasound may identify stones but ultrasound is generally less reliable for small stones and small kidney masses. Ultrasound is a poor study to identify any small cancer or stone within the ureters (tubes that carry urine between the kidneys and the bladder). Ultrasound is okay, but may not be as accurate as CT at identifying masses and stones. Ultrasound also is not as reliable as IVP in determining kidney function or finding small masses within the lining of the ureters.
A niche for ultrasound is that it is very good for evaluating dilation or possible blockage of the ureters and it is very good for characterization of medium and large kidney cysts. Perhaps as many as 50% of older patients have kidney cysts. Cysts may be found in association with kidney cancer and some cysts may become cancerous. However, most kidney cysts are benign (non-cancerous) and of little consequence.
Retrograde Pyelography (RPG)
Another supplementary type x-ray known as retrograde pyelography (RPG) may be performed when other types of x-ray imaging do not delineate the necessary anatomical detail required to exclude serious abnormalities. Another indication for RPG is when patients cannot use IV contrast due to allergy or kidney insufficiency or kidney failure. Retrograde pyelography is usually performed in the operating room with the patient under anesthesia.
Cystoscopy (see below) is necessary for RPG to be performed. During the cystoscopy procedure iodinated (iodine based) contrast is injected inside the bladder and ureters, up to the kidneys. This type of study generally provides the best fine anatomical detail of the collecting systems (the portions of the upper urinary tracts where urine is located) of the kidneys. Even in patients who have allergies to IV contract, there is usually no allergic reaction to the contrast used in this way. With RPG, contrast is not injected into the bloodstream. Rather, the RPG contrast is injected directly inside the urinary tract.
In addition to x-ray studies patients with hematuria generally require endoscopic evaluation by means of cystoscopy or even ureteroscopy. Cystoscopy is generally performed in the office with minimal anesthesia. A small flexible light is passed into the bladder through the urethra. This is generally painless, unless there is inflammation or anatomical deformity of the lower urinary tract. It is necessary to look into the bladder because many of the aforementioned x-rays are not reliable enough to exclude small cancers, stones and other abnormal findings associated with the bladder.
Ureteroscopy on the other hand is an endoscopic study which is generally performed in the operating room. A small flexible or rigid light is passed through the urethra and through the bladder then into one or both ureters. This allows direct visualization of nearly every portion of the upper urinary tract collecting systems (the portions of the upper urinary tracts where urine is located).
Cytology and Fluorescent in situ Hybridization (FISH) Studies
In addition to x-rays and endoscopic evaluations other urine tests are sometimes used. Cells lining the urinary tract are continuously shed into the urine. These “transitional cells” cells may be isolated from urine specimens. In selected patients urine specimens may be sent for very specialized pathology examinations, including assessment of the morphology (size, shape) and intracellular detail. The studies include urinary cytology, fluorescent in situ hybridization (FISH) analysis, as well as other so-called tumor marker studies. These very sophisticated tests are performed by outside specialized laboratories (rather than in the doctor’s office).
Unfortunately, even with a high degree of technical sophistication, these tests are commonly inconclusive. False-negative results may suggest that the cells isolated from the urine are normal, yet cancer may be present. False positive results may suggest that the cells are abnormal, when really no cancer is present. Nondiagnostic results may occur when the submitted urine specimen does not contain adequate numbers of cells to perform the requested specialized pathology test. Inconclusive results are fairly common. In these situations, the findings are often described as ‘atypical’ and the pathologist is simply unable to provide any clear answer as to the nature of the urinary tract problem.
Biopsy means removal of a tiny portion of an abnormal upper urinary tract mass. The tissue thus obtained is sent for pathology microscopic examination and special staining with the goal of making a definitive diagnosis. Sometimes this strategy is successful and sometimes it is not.
Upper urinary tract biopsies are usually obtained using ureteroscopy (see above). This requires a procedure in the operating room, under an anesthetic. Still, the biopsy may be inconclusive.
Kidney biopsies are most often performed by a radiologist, using a needle and CT guidance. Many pros and cons must be taken into account, when considering this option.
Some biopsy pros are:
(1) If enough tissue can be obtained and the tissue shows cancer, there is a good likelihood that the diagnosis is correct. This situation may lead to aggressive treatment (like surgery).
(2) If enough tissue can be obtained with the biopsy and the tissue is normal (showing no definite cancer or other abnormality), this could mean that there is no cancer. This may lead to continuing x-ray observation without aggressive treatment.
Some biopsy cons are:
(1) Biopsy results may be inconclusive. This leaves the patient in the same situation as before the biopsy, not knowing with certainty what treatment decision to make.
(2) Biopsy results may be falsely negative. This means that the biopsy results may be wrong! That is, the biopsy results may show ‘normal’ tissue (showing no cancer or other abnormality); yet, cancer (or another serious abnormality) may actually be present. This may lead patients into a false sense of security.
(3) Biopsies may cause bleeding, potentially leading to surgery or other forms of invasive intervention to stop bleeding. In general, severe bleeding with renal biopsy is uncommon, but possible.
(4) Biopsies may theoretically (rarely) spread cancer along a needle tract.
Follow-up for the Hematuria Patient
Despite comprehensive evaluation for blood in the urine, many patients (commonly those with only microscopic hematuria) are not found to have a clearly identifiable abnormal. This is to say that many patients with microscopic hematuria are not found to have an identifiable problem. Yet we know that if these patients are carefully followed over time, some of them may later be found to have cancer, kidney disease, kidney stones or another serious disease.
Thus, for all patients with hematuria, long-term follow-up by the urologist is mandatory. Patients with hematuria (of any type) must follow-up with the urologist, even when no abnormality is found on evaluation. This is the patient’s most important responsibility.
Should you visibly see blood in the urine, notify the urologist. Sometimes when the source of the bleeding cannot be otherwise verified, cystoscopy may be helpful at that very time. This may be helpful in identifying the bleeding source.
A special note should be made concerning patients who smoke or have smoked in the past. Smoking and aniline dye chemical exposure may cause cancer of the lining of the urinary tract (transitional cell cancer). Hematuria may be a sign of this type of cancer. The increased cancer risk even applies to patients who may have stopped smoking years ago. Thus for smokers, urology evaluation is most important.
Some patients may go on to see a nephrologist, a doctor who specializes in the evaluations and treatment of medical kidney problems. If a medical disease of the kidneys is suspected, a kidney biopsy may be required. This is rarely the case. No matter the findings, follow-up with urology is mandatory.
The causes of blood in the urine are many. A proven cause cannot be quickly identified in every case. Many causes of blood in the urine are benign, but cancer is a finding in some cases. Urology evaluation is needed in every case, nephrology evaluation is necessary in some cases and long-term follow-up is always important.