Evaluation and Management of Hematuria
Ecase #E-1
Lisa Oswald, M.D.
July 21-25, 2003

Case #1: A 28 yo male with HIV on HAART comes to see you in clinic with complaints of red urine.

1. What are some benign causes of hematuria that you should exclude?
2. What do you want to focus on in the history and physical?
3. What is the definition of microscopic hematuria?
4. How much blood is needed to cause gross hematuria?
5. He asks you whether normal people can get blood in the urine?
6. What are some of the common causes of hematuria?

Case #2: You are seeing a 77 yo female for a hospital follow up after pneumonia. You are checking her hospital labs and notice a urinalysis from during her admission. It shows 2-5+ RBCs otherwise normal. Her PMH includes osteoarthritis, tobacco use, and CAD. Meds include glucosamine, atenolol, and ASA.

1. What is the prevalence of microhematuria?
2. What are the risk factors for bladder carcinoma?

Case #3: A 62 yo male comes to you for a yearly physical. He is quite healthy except for 50 pack-year tobacco use, moderate hypertension and a prosthetic mitral valve for which he takes coumadin. You perform a H&P and give him a lab slip. He asks whether you want to get a urine sample too while you’re at it (he has no concerning symptoms nor history of gross hematuria).

1. What do you tell him?
   
   One year later you see him back in clinic. While you’re going through his ROS he remembers that he had an episode of gross hematuria 3 months ago that he meant to call you about. His INR around that time was 2.7.

2. What role does coumadin play in your assessment of his hematuria?
   
   You recheck a UA to distinguish glomerular versus extraglomerular hematuria.

3. What would you expect to find with glomerular bleeding? Extraglomerular?
   
   His UA is completely normal. You know that everyone with gross hematuria should have a work-up.

4. How do you want to evaluate his urinary tract?

5. What are your radiographic options?

6. What are the pros and cons of each?

7. What are the chances that you’ll discover a malignancy during his workup?

8. What might you consider if the above workup is negative?
   
   The patient ends up having BPH and more episodes of gross hematuria before seeing you back in clinic.

9. How do you want to treat him?

10. How does BPH cause hematuria?

Hematuria Answers

Case 1:

1. Benign causes include menstruation, physical activity, sexual activity, trauma, and infection. If you suspect one of these you should recheck a urinalysis after precipitating cause has ceased for 48 hours.

2. Historical symptoms: menstruation/pregnancy, dysuria, gross hematuria, clots, systemic symptoms, joint complaints, vaginal/penile discharge, meds, sickle cell disease or trait, family history, obstructive symptoms. Physical exam: BP, murmur/arrhythmia, abdominal masses, edema, prostate lesions, external genitalia, and urethral meatus.

3. Microscopic hematuria is generally defined as 3 or more RBCs on urinalysis. The sediment is the gold standard. There is no safe lower limit. Hematuria is also quite intermittent, even with malignant lesions, so many people recommend checking 3 samples if there is a high suspicion for lesions. The yield for malignancies is higher in patients with gross hematuria than for microscopic hematuria.

4. As little as 1mL.

5. Common to have transient hematuria in normals: reports range from 4-18%.

6. Common causes include: UTI, neprholitiasis, exercise, trauma, endometriosis, hemaglobinopathies, polycystic kidney disease, malignancies (bladder, kidney, prostate), BPH, glomerular disease, and transient unexplained hematuria.

Case 2:

1. Microhematuria prevalence ranges widely with figures from 0.19%-21%.

2. Risk factors: age>40, tobacco use, exposure to benzenes or aromatic amines, history of urologic disease, irritative voiding symptoms, hx UTI, analgesic abuse, and pelvic irradiation. Incidence rises sharply after age 50 and is more common in men.

Case #3:

1. Screening is not recommended since there is a fairly low prevalence of early disease, hematuria may not be sensitive for early disease, and early treatment may not result in a better prognosis. Some enthusiasm for home dipstick screening (very cheap=about $20 per year) comes from data showing early detection with this method.

2. He should be evaluated like all others (anticoagulation should not cause hematuria). In a group of 243 patients followed for 2 years, rates of hematuria were similar in coumadin and control groups.

3. RBC casts are pathognomonic for glomerular disease but not sensitive. According to 2001 AUA Best Practice Guidelines, dysmorphic red cells >80% suggests glomerular origin, whereas <20% suggests lower tract origin. However, some studies question the specificity since patients may have dysmorphic red cells with intrarenal but extraglomerular processes.

4. labs: basic chemistry panel, CBC, urine cytology, urine eosinophils, coags, culture if appropriate, SPEP/UPEP if appropriate. If glomerular disease: 24 hour urine protein, ANA, anti-GBM, complement, cryoglobulins, ASO titer, hep B surface antigen, VDRL, HIV serology. High risk patients without apparent risk factors for renal disease should undergo full urologic workup including upper tract imaging (see ‘e’ below), voided urinary cytology, and cystoscopy. Low risk patients with microhematuria only (no gross hematuria) should probably undergo a more stepwise workup (after repeating the urinalysis if a benign cause is suspected) although there is some uncertainty about this (see AUA guidelines).

5. Radiographic options include IVP, ultrasonography, and CT.

6. Due to lack of data, there are not currently evidence-based guidelines for imaging.
   
   From Grossfiled paper:
   IV urography: most cost-effective, best initial study of urinary tract. Less sensitive for renal masses; cannot distinguish solid from cystic masses. This has been traditionally the first imaging modality, though this may be changing in the future (toward CT?).
   
   Ultrasonography: low risk, high sensitivity for renal cysts. Less sensitive for small solid lesions.
   
   CT KUB (with ?and without contrast): best for detecting stones and solid renal masses. May need contrast if stone not detected by noncontrast CT.

7. 1% for all groups studied up to 8-9% for some older populations. In one paper by Mariani et al, 1000 patients with asymptomatic micro or gross hematuria without significant proteinuria=prevalence of 8.4% of malignancies.

8. Unexplained hematuria: 50% have glomerular disease (usually IgA nephropathy or thin basement membrane disease). Also consider hypercalciuria/hyperuricosuria, AVM, and loin pain-hematuria syndrome. About 1% of older patients with a negative workup with have a malignancy found in 3-4 years. Patients with asymptomatic microhematuria should be followed with repeat UA, BP, and cytology every 6 months for 3 years if they have risk factors for transitional cell carcinoma since hematuria can precede bladder cancer by many years.

9. Finasteride has been shown to decrease BPH-related hematuria. It blocks 5-alpha-reductase, blocking testosterone conversion and decreasing prostate size. It decreases risk of recurrent hematuria, surgery needed for hematuria, and increases urinary flow rates. Men with BPH and hematuria should have a work-up as above until other causes can be excluded.

10. New vessels associated with proliferation of BPH are fragile.

References

1. Cunningham G, Kadmon D. Treatment of benign prostatic hypertrophy. UpToDate 2002.

2. Grossfield G, Wolf J, Litwin M, Hricak H, Shuler C, Agerter D, Carroll P. Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations. American Family Physician 2001; 63:1145.

3. Lang E, Macchia R, Thomas R, Ruiz-Deya G, Watson R, Richter F, Irwin R, Margerger M, Mydlo J, Lechner G, Cho K, Gayle B. Computerized tomography for the assessment of microscopic hematuria. Journal of Urology 2002; 167:547.

4. Mariani A, Mariani M, Macchioni C, Stams C, Hariharan A, and Moriera A. The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. Journal of Urology 1989; 141:350.

5. Messing E, Young T, Hunt V, Emoto S, Wehbie J. The significance of asymptomatic microhematuria in mend 50 or more years old: findings of a home screening study using urinary dipsticks. Journal of Urology 1987; 137:919.

6. Rose B, Fletcher R. Evaluation of hematuria. UpToDate 2002.

7. Schramek P, Georgopoulos M, Schuster F, Porpaczy P, Maier M. Value of urinary erythrocyte morphology in assessment of symptomless microhaematuria. The Lancet 1989; 1316.

8. Sutton J. Evaluation of hematuria in adults. JAMA 1990; 263:2475.