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AD 10/02

Hematuria

Key Points:

1. A careful history may delineate the cause of hematuria.

2. Initial evaluation after hematuria is confirmed should include urine microscopy, urine culture, and

creatinine.

3. Pts who are at higher risk should be studied with IVP, urine cytology, and cystoscopy.

How do we define hematuria? No definitive cut-off of number of RBC per hpf, but >2 commonly accepted. To see gross hematuria, you need approximately 1mL blood per liter of liquid. Microscopic vs gross hematuria does not reliably predict benign or malignant process.

How can I be sure red urine is hematuria? Centrifuge the sample! If the supernatant is clear, then hematuria is likely responsible. If the supernatant is red, test it with a dipstick. Negative dipstick of supernatant suggests ingestion of beets, use of phenazopyridine (analgesic for bladder), porphyria, or other rare causes. Dipstick positive supernatant represents myoglobin or hemoglobin in the urine.

How good is the dipstick? Not bad. Can detect 1-2 RBCs for hpf, but does have a false positive rate. Because its sensitivity is so good, a negative dipstick essentially rules out hematuria.

What is the prevalence of serious urologic disease with hematuria? In pts with asymptomatic microscopic hematuria, risk of neoplasm, calculi, hydronephrosis is 2.3%. Risk of bladder or renal cancer is 0.5%.

What are the causes of hematuria? Glomerular: Acute GN can present as sudden onset of hematuria, proteinuria, RBC casts. RBC casts are pathognomonic for glomerular disease. Absence of these findings does not r/o glomerular disease. Look at the urine, as dysmorphic RBCs point to the glomerulus. Blood clots are a clue that this is NOT glomerular, as the urokinase and TPA activators in the glomeruli and tubules prevent clot formation.

Renal (non-glomerular): 90% of tumors are renal cell. Only 4% of renal cell cancer cases occur before age 40. Early detection may greatly improve survival. PCKD and hereditary nephritis can also cause hematuria.

Postrenal: Consider stones, infection, cancers. Excellent prognosis for TCC if detected early, although 22% of cases of transitional cell cancer are not associated with hematuria.

Hematologic: Therapeutic anticoagulation or antiplatelet therapy does not cause hematuria. Must r/o underlying disease. Pts with sickle cell trait or disease are at risk for papillary necrosis causing hematuria.

Other: Exercise or trauma (the Foley!) induced hematuria, endometriosis of urinary tract, “loin pain hematuria”.

What about BPH? Controversial if hematuria is more common than in age-matched controls. Some believe that enlarged prostate is associated with increased vascularity and that rupture of these tiny vessels can lead to hematuria. Work-up for other causes should still proceed. If everything negative, an alpha blocker may resolve the hematuria.

Any special questions on history? Ask about dysuria, frequency, urgency to elicit infectious or obstructive causes. Consider when the bloody urine appears during urination (ie early in stream suggests urethral origin and later suggests bladder).

AD 10/02

Relation to menstrual cycle, heavy exercise, or trauma is helpful. Recent URI might point to IgA nephropathy; with post-strep GN there is a latency of 7-10 days. Finally, don’t forget family history!

What should I focus on during the exam? Look at the urethral orifice for blood. Examine the belly, check for CVA tenderness. Consider signs of acute GN (ie HTN, volume overload). Do the prostate exam to feel for masses and tenderness.

How urgent is the work-up? Transient hematuria is common, with 39% of men ages 18-33 having at least one episode of hematuria on yearly urinalyses and 16% having two episodes. Most have no identifiable cause. Once patients get older, the risk of malignancy goes up. Some studies for men over 50 found that 8-9% of pts with intermittent hematuria had GU malignancy.

Are there any basic labs I should send once hematuria has been confirmed? Urine culture (to r/o bacterial infection)

BUN, Creatinine. Separate w/u for renal insufficiency.

UA micro on fresh specimen. Pyuria suggests infection/inflammation. RBC casts suggest GN. Dysmorphic RBC on phase contrast microscopy suggests renal origin.

Proteinuria. If urine dip protein > 1+, do 24 hr urine for protein. For substantial proteinuria, consider IVP to r/o renal causes, e.g. reflux nephropathy, renal TB, papillary necrosis, renal cell cancer. If IVP negative, then likely GN.

What about all those fancy studies? IVP: A reasonable first choice, especially good for young pts, as can detect lesions such as medullary sponge kidney which U/S won’t pick up. Test is 95% sensitive for detecting renal anatomic abnormalities. In patients with a contrast allergy or in older pts with a negative IVP, U/S or CT to r/o small renal tumors is appropriate.

Urine cytology: Detects 95% of grade III and invasive bladder tumors. Sensitivity decreases for upper tract disease. In pts with higher risk of bladder cancer (ie older, smokers, lots of smoked foods, long-standing cyclophosphamide), negative cytology should be followed by cystoscopy.

Cystoscopy: Recommended for higher risk patients. If find lower tract disease on cystoscopy , the upper tracts should also be evaluated due to “field cancerization effects”.

Renal biopsy: Consider this in pts with glomerular causes of hematuria, as yet undefined. Since there are risks to biopsy, this should be discussed with the nephrologist.

What if all studies are negative?

! 50% with idiopathic hematuria have glomerular disease. Consider IgA nephropathy or thin basement membrane disease.

! Hypercaliuria and hyperuricosuria: can lead to hematuria, even if no obvious stone disease. Often assoc’d with a positive family history. Treatment with thiazides for hypercalciuria or allopurinol of hyperuricosuria might resolve hematuria.

! AVMs: rare. Usually presents with gross hematuria, but can see high-output failure or HTN due to activation of renin-angiotensin system.

! Loin-pain hematuria syndrome: Not well understood. Characterized by loin or flank pain with dysmorphic RBCs in urine. Some feel there is a strong psychologic component to the pain. Hematuria may be due to thin basement membrane disease.

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How should I follow these patients? If all studies are normal, there is still a 1% risk of malignancy in older patients after 3-4 years of follow-up. Repeat cytology and urinalyses at 6-12 month intervals is advisable. A follow-up U/S and cystoscopy at one year is recommended by some urologists.

Should I screen for hematuria? No. Due to relatively low prevalence of disease, it is not recommended that we screen for hematuria.