Hematuria

Hematuria

I. Problem/Condition.

Hematuria means blood in the urine. It may be obvious from simply looking at the urine (gross hematuria), or incidentally found on a urinalysis and/or a urine sediment (microscopic hematuria).

For the busy hospitalist, usually only gross hematuria receives attention because it prompts an action, such as calling urology after a Foley catheter was placed traumatically, or calling nephrology to see if the patient needs a kidney biopsy to rule out a treatable glomerulonephritis.

Microscopic hematuria, however, is a potentially important finding that should be taken seriously. Though it is often due to benign or transient causes, it can also sometimes be the first sign of a pathologic process such as a glomerulopathy or cancer; even if the hematuria is not worked up in the inpatient setting, a plan for follow-up should be made with the primary care doctor and potentially a urologist.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

Traditionally, the differential diagnosis for discolored urine suggestive of hematuria can be divided up into a few major categories, depending on whether or not there is actually blood in the urine, and then depending on the anatomic source of the bleeding (the renal vasculature, the kidney, the upper urinary tract, or the lower urinary tract):

• Spurious (discolored urine not due to blood): beets, medicine discoloration of the urine, porphyria. Heme-positive urine dipstick but no red blood cells (RBC) on the sediment: lysed RBCs in a dilute, old or alkaline urine sample, myoglobinuria due to muscle breakdown, hemoglobinuria due to hemolysis, or the presence of semen in a post-coital sample.

• Intrarenal: kidney stones, renal cancer, kidney trauma, exercise, glomerulopathies (such as ANCA positive vasculitis, anti-glomerular basement membrane (anti-GBM) disease, immune complex disease, thin basement membrane disease, Alport’s syndrome), other intrinsic kidney disease (such as acute tubular necrosis, acute interstitial nephritis, small vessel disease), renal cyst, polycystic kidney disease, papillary necrosis.

• Renal Vasculature: renal vein thrombosis, renal artery stenosis, renal arteriovenous fistula, nut-cracker syndrome.

• Extrarenal: contamination (i.e., during menstruation), endometriosis of the urethra, kidney stones, bladder cancer or infection, prostate cancer/hypertrophy/infection, urinary tract infection of any kind, Foley catheter trauma, vesicoureteral reflux, radiation cystitis, bladder diverticulum, bladder neck contracture, interstitial cystitis, cystocele, urethrocele, neurogenic bladder, cystitis cystica/glandularis, eosinophilic cystitis, phimosis, duplicated collecting system, bladder neck polyps, urethral polyps, bladder varices/telangiectasias, trabeculated bladder.

• Only rarely is hematuria due to a bleeding disorder (coagulopathy), that is, if there is evidence of a massive bleeding disorder with bleeding at multiple sites.

B. Describe a diagnostic approach/method to the patient with this problem

When confronted with hematuria, consider the following elements: is it gross or microscopic, does the urinalysis show heme positivity and does the spun sediment show RBCs, does the urinalysis also show protein, is there evidence of a rising creatinine clearance, and what is the patient’s age and medical history? Consider the following:

• First characterize the hematuria as gross hematuria versus microscopic hematuria. Gross hematuria should then be characterized as containing clots or not, as clots almost always signify a lower urinary tract problem (i.e., not involving the kidneys). Traumatic Foley catheter placement is the most likely cause of clotting gross hematuria in the hospital setting. There exists a “Gross Hematuria Grading Scale” that can be downloaded to a smart phone to help communicate the severity of the hematuria to other team members. Making note of brown or “cola-colored” gross hematuria is helpful as this suggests a glomerular bleed.

• For non-clotted gross hematuria and microscopic hematuria, look at the urinalysis and spun urine. Discolored urine that is both heme-negative on urinalysis and RBC-negative on sediment analysis is likely due to a food (such as beets), a medicine (such as Pyridium), or porphyria.

  A urine sample that is heme-positive, but RBC-negative, is either myoglobinuria or hemoglobinuria, which can be found in rhabdomyolysis or hemolysis, a post-coital sample where the presence of semen has caused a false-positive heme test, or hematuria in which the RBC’s have lysed in the sample if the urine is very dilute, old, or alkaline.

  Finally, if urine is both heme- and RBC-positive, then there is true hematuria.

• With true hematuria, look to see if there is protein found in the urinalysis, kidney dysfunction through a rising creatinine, or evidence of abnormal cells such as dysmorphic RBCs or RBC casts. Although not always the case, proteinuria usually suggests that there is an intrarenal cause of the hematuria. Protein found on urinalysis can be further quantified with a urine protein/creatinine ratio or a 24-hour urine protein test. It is helpful to note whether the patient had proteinuria at baseline and whether this proteinuria represents a significant increase.

  Evidence of worsening kidney function will help confirm that the process is intrarenal. Similarly, looking at the morphology of the RBCs will help as the presence of dysmorphic RBCs or RBC casts are virtually pathognomonic of a glomerulonephritis. Acanthocytes (ringlike RBCs with protrusions coming off of them, best seen with phase contrast microscopy) are particularly important to note.

  Nephrologists may differ on when they recommend a renal biopsy (e.g., if the proteinuria reaches a certain number of grams per day), but suspicion for any intrarenal cause of hematuria certainly warrants a nephrology consult. Of note, lone persistent glomerular hematuria, without evidence of renal insufficiency or systemic disease may be IgA nephropathy, Alport’s syndrome, or thin basement membrane disease, all of which may not need a biopsy to be followed initially (but a nephrologist can assist in determining the need).

• Look for evidence of pyuria (greater than 5-10 white blood cells (WBC)/hpf) with the hematuria. Pyuria can be divided up into culture-positive pyuria or sterile pyuria. Culture-positive pyuria is usually caused by a urinary tract infection [UTI]. Sterile pyuria may be due to an improperly cultured UTI, contamination of leukocytes from a genital infection, prostatitis, acute interstitial nephritis, glomerulonephritis, analgesic nephropathy, atypical organisms such as Renal TB/Chlamydia/Ureaplasma urealyticum, bladder cancer or nephrolithiasis. Diagnosis of a true UTI or pyelonephritis should be guided by the presence of symptoms suggestive of an infection (dysuria, increased frequency, fever, costovertebral angle tenderness, etc.) (see the chapter on UTI).

• Assess the patient’s risk for cancer. The general rule of thumb is that the patient is at greatest risk of cancer as a cause of his or her hematuria when he or she is more than 40-50 years old, and/or has been exposed to elements that increase risk: history of tobacco use (maybe even second-hand smoke exposure from tobacco or prior use of wood-burning stoves if the exposure is significant); exposure to known carcinogenic agents or chemotherapy, such as alkylating agents (particularly cyclophosphamide); pelvic radiation; chronic analgesic use; occupational or other exposure to chemicals or dyes; gross hematuria; known urologic disorders or disease; irritative voiding; use of some Chinese herbs; certain bladder infections, such as chronic cystitis or Schistosoma haematobium; or a chronic indwelling foreign body.

  For chemical exposure, certain occupations may be associated with specific agents. Polycyclic aromatic hydrocarbons may be a risk to chimney sweeps, nurses, and waiters, as well as aluminum, ship, and oil/petroleum workers; aromatic amines may be a risk for tobacco, dye, rubber, and leather workers, hairdressers, and printers.

• Work it up appropriately. A full urologic work-up with assistance from a urologist would include imaging of the upper urinary tract with CT (multiphasic CT urography without and with IV contrast), and testing of the lower urinary tract with cystoscopy. In a 2012 set of guidelines, the American Urologic Association advised that all patients greater than 35 years old with 3 or more RBC/hpf should get both a CT with IV contrast and cystoscopy. Adherence to these guidelines has been quite low, probably because hematuria is so common (up to 13% of the general population can have microscopic hematuria, 2.5% can have gross hematuria) and the chance that the hematuria is from bladder cancer is not the most likely scenario (one retrospective study found urinary tract tumors in only 10% of patients presenting with gross hematuria and only 3% of patients presenting with microhematuria). Ordering of these studies should be balanced with the potential harms, including exposure to radiation, allergic reactions to contrast, contrast-induced nephropathy, the added expense, the chance of finding incidental findings that only provoke anxiety and further testing, and the risks associated with cystoscopy.

  Gross hematuria is more likely to yield a diagnosis of bladder cancer and is associated with finding cancer at a more advanced stage, so it should nearly always prompt the consideration of a thorough work-up. There remain important controversies in the work-up of asymptomatic microscopic hematuria, including at what age to start it (35, 40, or older), whether patients without risk factors for cancer can avoid getting a CT and its associated radiation or avoid getting a cystoscopy, whether urine cytology or urine genetic testing will assist in the work-up, how often to repeat testing if no cause is found for persistent hematuria, and whether there should be different algorithms for men and women.

  As a result of these controversies, researchers are actively looking to validate decision support tools and new urine genetics tests to assist with risk stratification. Such risk indexes or biomarkers are not yet used in common practice but the following gives a sense of how one hematuria risk index might work: the greatest weight would be put on the presence of gross hematuria (as opposed to microscopic hematuria) and age >50; less weight would be put on a history of smoking, male gender, and >25 RBC/hpf. Based on these variables and weights, patients could then be stratified into high, middle, or low risk and worked up accordingly. Until such practices are used in common practice, generalist clinicians should work with urologists to get their expert opinions on how to best manage these patients.

  In addition, practices differ as to whether a patient who has a known glomerular cause of hematuria should also get a further work-up for possible genitourinary cancer. Many would argue that any hematuria with risk factors for cancer should be worked up accordingly because it is always possible that two processes are occurring simultaneously. A similar question exists for patients who are found to have a bladder tumor on cystoscopy; they will likely still need CT imaging to ensure that cancer is not present in other parts of the urinary system.

  If the presence of risk factors prompts a work-up for possible bladder cancer, CT with and without IV contrast (CT urography) are the best imaging studies. If the patient cannot get a CT and/or IV contrast, MR urography is an alternative. If the patient cannot get IV contrast or an MRI, a combination of non-contrast CT or renal ultrasound with retrograde pyelograms is another alternative, but these decisions should be made in consultation with a urologist and a radiologist.

• If the above questions do not yield a clear diagnosis, consider other historical clues that may point to another diagnosis (see “Key Historical Elements”).

• If no cause is immediately found, the hematuria should be followed to resolution or to see if any of the possible diagnoses become likely over time (i.e., if renal failure or hypertension develops, if there are other new systemic symptoms to suggest a specific diagnosis, etc.). How often to re-sample the urine will depend on the patient’s risk factors and the clinical scenario.

  If the diagnosis continues to be negative, rarer causes of hematuria can be considered: hereditary hemorrhagic telangiectasias, radiation cystitis, arteriovenous malformations, fistulas, nutcracker syndrome (compression of left renal vein between the superior mesenteric artery and aorta), loin-pain hematuria syndrome (a rare, poorly understood syndrome affecting mostly young white women), urinary tract endometriosis, polycystic kidney disease, sickle cell disease, renal infarcts, etc. Also possible is hypercalciuria and hyperuricosuria.

• Patients at high enough risk for cancer, but with a negative initial evaluation, would best be followed with a serial urinalyses, potentially in conjunction with a urologist. Urine cytology may play a role with high-risk patients whose initial testing is negative or equivocal, but urine cytology for the work-up of microscopic hematuria is increasingly losing favor as a test because of the low sensitivity, high cost, and the need for a pathologist who is trained in test interpretation.

1. Historical information important in the diagnosis of this problem.

Gross hematuria- with clots

If the patient recently had a Foley catheter placed, then this is the most likely culprit. If they did not have a Foley placed, then the patient likely has a spontaneously bleeding lesion in their lower urinary tract not involving the kidney.

Gross hematuria- without clots, and microscopic hematuria

Again, recent Foley placement is an easily identifiable culprit. If the patient does not have a Foley, or the Foley was placed too long ago to be relevant, and there has not been any Foley trauma since placement, then aside from the diagnostic process described here, certain elements of the history could help to point towards a diagnosis (see “Key Historical Elements that are likely to be useful in diagnosing the cause of the problem”).

Differential for hematuria per the patient's age

Although almost any disease can affect anyone at any age, epidemiology helps us guide our diagnostic process to hone in on the most likely cause:

• Age below 20, any gender: glomerulopathies (especially IgA nephropathy, thin basement membrane disease), urinary tract infection, congenital malformation, hereditary nephritis (Alport’s Syndrome), sickle cell disease.

• Age 20-60, any gender: urinary tract infection, nephrolithiasis, endometriosis (if female), cancer (with 35-50 years old being the ages where risk starts to increase most).

• Age over 60, male: cancer (especially bladder cancer, prostate, or renal cell carcinoma), prostatitis, urinary tract infection.

• Age over 60, female: cancer (especially bladder cancer or renal cell carcinoma), urinary tract infection.

2. Key historical elements that are likely to be useful in diagnosing the cause of this problem.

• Transient hematuria: a common finding often due to fever, trauma, exercise, but in patients older then 40-50 years old, cancer is also possible.

• Concurrent menstruation in a female patient: consider contamination.

• Recent red food consumption or new medicine: consider spurious discoloration of the urine (see lists in “Criteria for Diagnosis”).

• History of, or clinical suspicion for, porphyria: consider porphyria causing discolored urine that is not true hematuria.

• A history of endometriosis: consider endometriosis of the urinary tract.

• Recent Foley placement or manipulation: likely due to trauma from the catheter.

• Hematuria with blood clots: usually due to a lower urinary tract source, but can also be due to an invasive kidney cancer; glomerular bleeding does not usually cause clots.

• Recent trauma (i.e. a punch to the flank) or vigorous exercise (e.g., running a marathon): consider kidney trauma or exercise.

• A family history of hematuria, renal failure, corneal abnormalities, deafness: consider hereditary nephritis (Alport Syndrome).

• A family history of hematuria and kidney disease: could be polycystic kidney disease, thin basement membrane disease.

• Is the patient over 40-50 years old, with a risk factor for cancer: history of tobacco use (maybe even second-hand smoke exposure from tobacco or prior use of wood-burning stove if the exposure is significant); exposure to known carcinogenic agents or chemotherapy, such as alkylating agents (particularly cyclophosphamide); pelvic radiation; chronic analgesic use; occupational or other exposure to chemicals or dyes; gross hematuria, known urologic disorder or disease; irritative voiding; use of some Chinese herbs; certain bladder infections, such as chronic cystitis or Schistosoma haematobium; chronic indwelling foreign body). Bladder cancer is possibly more likely.

• Urinary frequency, dribbling in an elderly gentleman: benign prostatic hypertrophy (BPH) or prostatitis is possible.

• Are there signs of a nephritic or nephrotic syndrome (such as heavy proteinuria, lipiduria, or a “cola brown” discoloration of the urine)? Most likely cause is an intra-glomerular process.

• Hand and/or face swelling: could be a severe glomerulonephritis with nephrotic range proteinuria

• Recent upper respiratory infection: could be evidence of an IgA-nephropathy or post-infectious glomerulonephritis (poststreptococcal glomerulonephritis, or a nonspecific mesangioproliferative glomerulonephritis).

• Dysuria (aka “irritative voiding”): could be a UTI, may also be bladder cancer.

• Hematuria with pyuria with a positive urine culture (and dysuria): UTI.

• Hematuria with sterile pyuria: may be an improperly cultured UTI, contamination of leukocytes from a genital infection, prostatitis, acute interstitial nephritis, glomerulonephritis, analgesic nephropathy, atypical organisms such as renal TB/chlamydia/ureaplasma urealyticum, bladder cancer, or nephrolithiasis.

• Living in endemic developing countries: could be Schistosoma haematobium or renal tuberculosis.

• Terrible flank pain, sometimes radiating to the groin: nephrolithiasis is most likely, but cancer is also possible, as is the rare loin pain-hematuria syndrome.

• Elevated coagulation studies with bleeding from multiple sites: may be due to a coagulopathy, such as disseminated intravascular coagulation.

• Patient with African genetic roots: consider sickle cell disease (as microthrombotic events from sickle cells can lead to renal infarcts and papillary necrosis).

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Urinalysis and urine sediment are the first tests needed to confirm the presence of hematuria, and then hone in on the most likely culprit. The presence of RBCs (heme on the urinalysis, and RBCs on the sediment) and WBCs (leukocyte esterase on the urinalysis and WBCs on the sediment) are key important findings.

The urine sediment should be examined under a high power microscope by an experienced clinician who can confidently note the presence of dysmorphic RBCs or RBC casts.

Special attention should be paid to the presence of protein in the urine sediment, but a spot urine protein/creatinine ratio, sometimes even a 24-hour urine protein, may be needed to confirm the severity of proteinuria. If there is at least 1+ proteinuria on the urinalysis, it is reasonable to quantify the proteinuria with a 24-hour urine protein. Abnormal would be greater than 500 mg/day.

A blood serum creatinine level, along with an accurate height (to calculate an ideal body weight and then a creatinine clearance) will help to see if there is any element of kidney dysfunction.

Blood pressure should be measured and compared to the patient’s baseline value; any increase from baseline, even if still within a normal range, may be evidence of kidney dysfunction.

Depending on the findings, the patient may need a kidney biopsy, a multiphasic CT urography without and with IV contrast, a cystoscopy, or urine cytology (see diagnostic approach above).

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Most likely diagnosis, followed by the key diagnostic criteria (and follow-up advice):

Spurious discolored urine

Discolored urine that is both heme- and RBC-negative. This could be due to foods (especially beets, blackberries, or food dyes), porphyria, or a medicine (especially phenazopyridine (Pyridium), rifampicin, doxorubicin and daunorubicin, but also alpha-methyldopa).

Menstruation contamination

Menstruating women with incidentally found heme-positive on the urinalysis (UA) and many normal looking RBCs on the sediment. A tampon can be placed to prevent cross-contamination and a new urine sample collected. If the hematuria persists, another cause should be considered.

Foley catheter trauma

Usually gross hematuria with or without clots, heme-positive on the UA and many normal looking RBCs on the sediment. There should not be any proteinuria. Once the bleeding is controlled and the lesion heals, the hematuria should clear entirely or worked up appropriately.

Primary glomerulopathies

May be gross or microscopic hematuria, but in addition to being heme-positive on the UA, there should be proteinuria and there may be dysmorphic RBCs or RBC casts. A spot urine or 24-hour urine sample may show nephrotic range proteinuria. A creatinine clearance (either calculated or measured with a 24-hour urine sample) may show kidney dysfunction. A kidney biopsy will usually be necessary to make the diagnosis and prescribe the most effective treatment. The most likely diagnosis will include an IgA-nephropathy, or a glomerulonephritis (See chapter on GN). Work-up for genitourinary cancer should probably still occur if risk factors are present.

Acute interstitial nephritis

Hematuria with sterile pyuria and urine eosinophils that are seen with a special stain and other associated signs and symptoms. (See chapter on AIN).

Nephrolithiasis

The presence of true hematuria with flank pain should place the possibility of a stone high on the differential. Once the presence of heme on the UA and a normal RBC morphology on the sediment is noted, a “stone protocol” CT (without IV contrast) could be ordered to confirm the presence of a stone. A 24-hour urine sample, or a stone analysis, may be necessary later if the stone is recurrent. (See chapter on Kidney Stones)

Urinary Tract Infection (UTI)

In addition to heme on the UA and RBCs on the sediment, laboratory clues to the diagnosis of a UTI include leukocyte esterase or nitrite on the UA, WBCs on the sediment, and a positive urine culture. Pyuria is defined as greater than 5-10 WBC’s/hpf. Diagnosis of a UTI versus asymptomatic bacteriuria or sterile pyuria should be guided primarily by the presence of symptoms of a UTI (dysuria, increased frequency, etc.) The presence of fever suggests an “ascending” infection, namely pyelonephritis and/or a perinephric abscess.

Of note, gross hematuria may sometimes also contain pyuria simply because the blood leaking into the urinary space also contains WBCs. If the proportion of WBCs in the urinary blood approximates the proportion of WBCs in a cell blood count, then the WBCs may not represent true pyuria. (See chapter on UTIs)

Bladder cancer

Usually suspected from the presence of hematuria, the patient’s age and the presence of risk factors. It is then worked up with cystoscopy and multiphasic CT urography without and with IV contrast, and then confirmed on biopsy. Bladder cancer can be urothelial (i.e., transitional cell carcinoma) or nonurothelial (i.e., squamous cell carcinomas, adenocarcinomas, small cell tumors, sarcomas, pheochromocytomas, melanomas, lymphomas) in origin. (See chapter on bladder cancer)

Kidney cancer

The classic symptoms of flank pain, hematuria, and a palpable abdominal mass are actually not too common. More likely, the kidney mass is found on imaging as the hematuria is being worked-up. If the renal mass is invasive, the patient could have blood clots in their urine, but this is the only rare situation where a kidney cause of hematuria causes clots as glomerular bleeding usually does not cause clots. The diagnosis is confirmed on biopsy or nephrectomy. (See chapter on kidney cancer)

Coagulopathy

If the coagulation studies are grossly abnormal (such as in a warfarin overdose or disseminated intravascular coagulation) and there is evidence of bleeding from multiple sites, then the hematuria may be related to the coagulopathy, but this hematuria should still be evaluated the same way as in any other situation. Hematuria should never be simply blamed on the presence of anticoagulation (i.e., a novel oral anticoagulant, a high INR due to warfarin, heparin drip, anti-platelet therapy, etc.).

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome):

Suspected in the right clinical scenario (spontaneous and recurrent epistaxis, multiple mucocutaneous telangiectasias, first-degree relative with the disease, other visceral involvement).

Radiation cystitis

Suspected from the clinical history, confirmed on cystoscopy.

Arterio-venous-malformations (AVMs) and fistulas

Suspected on CT imaging, confirmed on arteriography or cystoscopy, usually treated with arterial embolization or surgery.

Nutcracker syndrome

Occurs with compression of the left renal vein between the aorta and the superior mesenteric artery. Suspected from the clinical history, confirmed on US Doppler of the renal vasculature or arteriography.

Loin-pain hematuria syndrome

Suspected from the clinical history. Characterized by flank pain and occasionally dysmorphic RBCs in the urine, it is difficult to confirm and manage (as psychosocial issues sometimes confound).

Endometriosis

A rare occurrence and usually suspected as a diagnosis of exclusion in a patient with a known history of endometriosis. The hematuria is usually cyclic and treatment of the endometriosis should resolve the hematuria.

Polycystic kidney disease

Usually evaluated for in the presence of a positive family history or found incidentally on imaging. The diagnosis is confirmed by renal ultrasound and genetic testing.

Prostate disease

Suspected from symptoms or a history of prostate disease, hematuria should only be blamed on the prostate after an otherwise negative work-up. In BPH, the use of finasteride usually clears up the hematuria (thereby further confirming the diagnosis).

Renal infarct

Can appear similar to the flank pain associated with a kidney stone, but on CT a renal infarct is found instead of a stone. (See chapter on renal infarct)

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

There are no universal guidelines on how to work up hematuria as there is not yet enough high-quality data to issue definitive recommendations. Different associations of urologists in different countries have issued very differing guidelines on how to proceed, and each algorithm often reflects that country’s health system, the society’s comfort with uncertainty, and the desire to address that uncertainty with increased health care spending and technology, even if associated with risks. In addition, older imaging techniques such as retrograde or intravenous pyelograms, and newer or more expensive techniques such as MR urography and urine genetic testing, are currently not being used regularly or are used in only special circumstances (such as patients with IV contrast allergies, pregnant women, etc.) In the face of this uncertainty, generalist physicians should seek the help of nephrologists and urologists as necessary.

III. Management while the Diagnostic Process is Proceeding

A. Management of hematuria.

Gross hematuria with clots after Foley placement

Call the urology department to have them place a Foley catheter that allows for saline flushes or continuous bladder irrigation. Once the clots clear, the Foley can be removed for a trial of voiding or may be kept in place until the patient can follow-up as an outpatient. Ultimately, the hematuria should be followed to resolution as persistent hematuria should be worked up as in any other patient.

Transient versus persistent microscopic hematuria (in young patients)

If hematuria is noticed in hospitalized patients less than 35-40 years old and there is no evidence of a UTI or kidney disease, it can usually be followed as an outpatient until resolution. Transient hematuria in young patients can often be due to exercise, fever, trauma, or infection. If the hematuria persists and there is evidence of glomerular bleeding, these patients can be referred to a nephrologist for the possibility of needing a kidney biopsy.

Around half will have thin basement membrane disease or IgA nephropathy, which in early stages have no specific treatment so many nephrologists will wait until there is evidence of renal insufficiency, new hypertension, or significant proteinuria, to even biopsy. If there is no evidence of an intrarenal cause of the hematuria, a urologist can assist with further work-up.

Transient versus persistent microscopic hematuria (in older patients)

If hematuria is noticed in patients older than 35-50 years old, there is no evidence of an intrarenal source, and the patient has risk factors for genitourinary cancer, even transient hematuria should be taken seriously as it could be an early sign of cancer. See work up suggestions above.

Glomerulopathies and tubular nephropathies

Management depends on the specific diagnosis (See chapter on GN)

Nephrolithiasis

Usually hydration, analgesics, and straining the urine to find a stone for analysis. (See chapter on kidney stone)

Urinary tract infections

Usually antibiotics, either empirically or as guided by the culture.

Sterile pyuria

Management as guided by the most likely cause. (See chapter on specific causes)

Bladder cancer/kidney cancer

See Chapter on Bladder cancer and Kidney cancer.

Coagulopathy

Correction of the coagulopathy by targeting the cause. The hematuria should be followed to resolution and worked up accordingly.

Prostate disease

Of note, in BPH, the use of finasteride may help resolve the hematuria.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

Even if the clinician is confident of the cause of the hematuria, it should be followed to resolution, as there might be two concurrent processes. For example, if a patient has a Foley placed and starts passing clots, it is not enough to only remove the Foley. Once the acute bleeding is controlled, a repeat urinalysis should be performed a few days after the Foley is removed, and then worked up accordingly.

Foley catheters can traumatize bladder cancers as easily as they can traumatize normal tissue. Similarly, hematuria associated with a UTI should be followed to resolution with a repeat UA in approximately 6 weeks. Even if a provoking etiology is suspected (such as trauma, menstruation, exercise, etc.), the UA should be followed to resolution once the provocative factor stops.

If hematuria persists and there is a potentially obvious cause in the patient’s history (such as an incidentally found simple kidney cyst), then these diagnoses should be considered diagnoses of exclusion until a formal and systematic work-up has been undertaken based on the patient’s risk factors.

An elderly man with BPH can also be hiding an early bladder cancer; hematuria in these cases is an early warning sign that could lead to an early diagnosis and clinical cure. Similarly, hematuria in a patient on anticoagulants should be worked up as with any other patient. A supratherapeutic INR or dual anti-platelet therapy should not be a reason to ignore unexplained hematuria.

The responsibility of finding dysmorphic RBCs should not fall to the laboratory, as the read may not be accurate. If in doubt, spin and look at the urine yourself if you have the appropriate training, or call nephrology to do the same. Ruling out dysmorphic RBCs on a urine sediment is a legitimate nephrology consult.

What's the evidence?

Davis, R, Jones, JS, Barocas, DA. “Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline”. The Journal of Urology. vol. 188. 2012;31. pp. 2473-81. (Standard guidelines from AUA.)

McDonald, MM, Swagerty, D, Wetzel, L. “Assessment of Microscopic Hematuria in Adults”. American Family Physician. vol. 73. 2006. pp. 1748-1754.

Yun, EJ, Meng, MV, Carroll, PR. “Evaluation of the patient with hematuria”. Med Clin N Am. vol. 88. 2004. pp. 329-343.

Chow, KM, Kwan, BC, Li, PK, Szeto, CC. “Asymptomatic isolated microscopic haematuria: long-term follow-up”. Q J Med. vol. 97. 2004. pp. 739-745.

Nielsen, M, Qaseem, A. “Hematuria as a marker of occult urinary tract cancer: Advice for high-value care from the American College of Physicians”. Annals of Internal Medicine. 2016. (This is a very good article giving advice on key clinical challenges that remain in working up hematuria while balancing risk and cost to patients and the health system, and the benefit of finding significant disease early.)

Kiragu, D, Cifu, AS. “Evaluation of patients with asymptomatic microhematuria”. JAMA. vol. 314. 2015; 3. pp. 1865-6. (Good standard review of the topic in a top journal.)

Niemi, MA, Cohen, RA. “Evaluation of microscopic hematuria: a critical review and proposed algorithm”. Advances in Chronic Kidney Disease. vol. 22. 2015;31. pp. 289-96. (Discusses the pros and cons of different strategies.)

Loo, RK, Lieberman, SF, Slezak, JM. “Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria”. Mayo Clinic Proceedings. vol. 88. 2013. pp. 129-38. (Cutting edge article trying to add greater evidence to decision support for working up hematuria.)

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