The Radiological Approach to the Patient With Hematuria
Written by: Jeffrey H. Newhouse, M.D.
May 1, 2001

INTRODUCTION
Hematuria is a frequent complaint, and a common reason to refer patients for imaging studies. Choosing which patients with hematuria to image and which modalities to use is important—not only from the standpoint of practicing good medicine—but also from the need for cost-effectiveness. It is odd that the literature does not seem to contain a firm consensus on whom to image and how; this essay will review the current state of the radiological art, and try to form recommendations.

For the purposes of this discussion, only adult patients will be considered. Patients in whom hematuria coexists with symptoms or signs which strongly suggest urinary tract stones, infection, or trauma, will not be discussed, nor will second-step imaging maneuvers (if initial techniques reveal lesions that need to be further characterized).

WHO TO IMAGE
In most practices, of course, the selection of patients to be imaged is not made by radiologists; instead, the population consists of patients referred by others. Nevertheless, it might be worthwhile to discuss appropriate selection of patients, not only for the education of our colleagues, but to encourage appropriate practice patterns. It would be easy to say simply that all patients with hematuria, or all patients with gross hematuria, or some other easily-defined group, should be imaged; unfortunately, the reality may not be so simple.

Very large numbers of patients have microscopic hematuria at one point or another in their lives, and have no detectable disease. It may be more of a semantic point to decide whether hematuria in these patients is "normal," but asymptomatic microscopic hematuria can be found so often in randomly screened populations, and the presumed yield of investigating them so low, that the cost-benefit ratio for a practice that images all patients with any degree of hematuria would be huge. Nevertheless, the most widely cited textbook on urology recommends such a practice, stating that any degree of hematuria, no matter how minor, raises the likelihood of malignancy and therefore a full work-up, including imaging, is mandatory. But at least one other paper, citing data from a very large population of screened patients, suggests that work-up may be necessary in very few (see references). With these disparate views, deciding how to practice can be difficult.

It might seem intuitive that gross hematuria is more likely to reflect important disease than microscopic hematuria but, even though that may be true, microscopic hematuria indicates important disease (at least in certain populations) sufficiently often that it cannot be ignored simply because it is not gross.

The referral sources of the particular patients are important to consider. The prevalence of important disease in a population with asymptomatic microhematuria may be relatively low in patients who are periodically screened by generalists. Those who are sent from urology practices are likely to have a higher prevalence of disease, presumably because some characteristic, in addition to the hematuria, motivated the generalists to send the patient to the urologist in the first place.

Certain simple and inexpensive methods may be used to identify patients who should definitely be imaged. Positive or indeterminate urinary cytology, family history of urological malignancy, smoking, exposure to certain chemicals, and symptoms of specific urological malignancies unquestionably require imaging. At the other extreme, young women with hematuria and cystitis, in whom the hematuria permanently resolves after treatment for the cystitis, may not need upper tract imaging. Patients with a single episode of hematuria following strenuous exercise may not absolutely require imaging if subsequent urinalyses show no red cells whatsoever. Patients with clinical and laboratory evidence of pure glomerular disease causing hematuria may not need urological imaging. However, renal ultrasound to determine size and parenchymal thickness, and chest radiography, are often called for in patients with glomerulonephritis.

Although anticoagulation therapy might be considered a cause of bleeding in patients without urological disease, investigations of this population suggest that hematuria may indeed reflect important urological disease—including malignancy—with sufficient frequency that dismissing it may not be prudent.

WHICH MODALITY TO CHOOSE
The question of which modality to use has received sporadic attention in the literature, but firm evidence favoring one in particular is not available. Up until several years ago, comparisons usually dealt with excretory urography and its several variations, transabdominal ultrasonography, and simple radiography. It might be expected that ultrasound would be better than urography in detecting cysts and small solid renal neoplasms that project from the anterior or posterior aspects of the kidney, and that excretory urography would be better at finding small flat lesions in the collecting system and ureter, but, although there are small series and anecdotal cases in the literature, firm support of these suppositions is not apparent. In any case, sonography performed for hematuria should probably be accompanied by radiography to find small stones (especially in the mid-ureter) which ultrasound might miss. Lack of firm evidence in the literature is due to several factors, including the difficulty of determining false-negative rates for any modality, sensitivity and specificity for individual diseases which have low prevalence, the definition of the population examined, the technical protocol, and so forth.

Whichever modality is chosen, it was (and remains) standard practice to perform cystoscopy in patients needing investigation. This is because both urography and ultrasound may fail to detect small flat inflammatory or neoplastic lesions in the bladder, however successful they might be in finding polypoid intraluminal lesions.

More recently, variations on techniques using computed tomography have been described and are rapidly becoming more popular. "CT urography" is the phrase which has become attached to these techniques, which always include CT (usually pre- and post- intravenous contrast) followed by some sort of pyeloureterography. The latter may be performed by one the following techniques:

• reformatting CT images obtained during the excretory phase
• using CT scout views
• moving the patient from a CT scanner to a radiography facility where pyeloureterography may be performed
• performing the CT immediately after a standard excretory urogram.

There have not been a sufficient number of large studies to determine which of these various techniques is best, and they continue to be evaluated. Until valid results are available, it would be prudent to assume that CT is the most sensitive and specific examination for detecting conditions which produce renal masses and renal cysts. CT should also be relatively accurate in finding medium-sized or large polypoid lesions in the hollow portions of the urinary tract, but it is unclear whether CT—reformatted or not—can detect small flat urothelial lesions, or diseases (such as mild papillary necrosis or medullary sponge kidney without calcifications) which produce very small anatomical abnormalities. Film-screen (or direct digital) pyeloureterography is likely to be as accurate after a CT study as it is during excretory urography. I suspect that within a very few years radiologists will determine whether the shift to CT urography is warranted.

MR urography should, at least in theory, match CT for detection of renal masses and the capacity to use reformatted images to create pyelouretograms. This examination is costly, however, and it remains uncertain whether the entire urinary tract can be imaged with sufficient spatial resolution to challenge CT urography.

If hematuria persists after initial cystoscopy and imaging, the next step can be problematic. Arteriography may reveal small arteriovenous malformations or other vascular abnormalities which bleed, but the prevalence of arteriovenous malformations is low, as is that of arteritis in patients who exhibit no abnormalities other than hematuria. Flexible ureteroscopes are becoming easier to use and less traumatic, so that patients whose ureters and collecting systems are not ideally visualized may have abnormalities revealed by this device.

CONCLUSION
Many adults with hematuria, either microscopic or gross, require imaging work-up. Only in specific circumstances, in which hematuria permanently resolves, may imaging be forgone. There is an ongoing switch from excretory urography and ultrasound to variations of CT urography; validation of these techniques is in progress. Cystoscopy maintains a role in the work-up of patients with hematuria, angiography is rarely necessary, and MR urography remains experimental.

REFERENCES

1. Froom P, Ribak J, Benbassat J. Significance of microhaematuria in young adults. Br Med J. 1984; 288 (6410):20-2.
2. Lowe FG, Brendler CB. Evaluation of the urologic patient. In Walsh PC, et al, eds. Campbell’s Urology, Philadelphia, PA:WB Saunders; 1992:307-317.
3. Messing EM, Young TB, Hunt VB, Emoto SE, Wehbie JM. The significance of asymptomatic microhematuria in men 50 or more years old: findings of a home screening study using urinary dipsticks. J Urol. 1987; 137(5):919-22.
4. Benson GS, Brewer ED. Hematuria: algorithms for diagnosis. II. Hematuria in the adult and hematuria secondary to trauma. JAMA. 1981; 246(9):993-5.
5. Copley JB. Isolated asymptomatic hematuria in the adult. Am J Med Sci 1981;291(2):101-111.
6. Abuelo JG. Evaluation of hematuria. Urology. 1983;21(3)215-25.
7. Sutton JM. Evaluation of hematuria in adults. JAMA. 1990; 263(18):2475-80.
8. Golin AL, Howard RS. Asymptomatic microscopic hematuria. J Urol 1980;124(3):389-391.
9. Chisholm RA, Millet B, Sherwood T, Wraight EP, Doyle PT. The investigation of painless hematuria- a comparison of intravenous urography and DMSA scintigraphy. Clin Radiol. 1988; 39(5):494-5.
10. Corwin HL, Silverstein MD. The diagnosis of neoplasia in patients with microscopic hematuria: a decision analysis. J Urol. 1988; 139(5):1002-6.
11. Murakami S, Igarashi T, Hara S, Shimazaki J. Strategies for asymptomatic microscopic hematuria: a prospective study of 1,034 patients. J Urol. 1990; 144(1)99-101.
12. Mariani AJ, Mariani MC, Macchioni C, Stams UK, Hariharan A, Moriera A. The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. J Urol. 1989;141(2) 350-5.
13. Mohr DN, Offord KP, Owen RA, Melton LJ. Asymptomatic microhematuria and urologic disease. A population-based study. JAMA. 1986; 256(2):224-9.
14. Barkin M, Lopatin W, Herschorn S, Comisarow R. Unexplained hematuria. Can J Surg. 1983; 26(6):501-3.
15. Thaller TR, Wang LP. Evaluation of asymptomatic microscopic hematuria in adults. Am Fam Physician. 1999; 60(4):1143-52, 1154.
16. Nishimura T, Abe H, Miura T, Uchikoba T, Tsuboi, N, Yamamoto H, Kobayashi K. Post-voiding repeated renal ultrasonography for slight hydronephrosis detected during screening for asymptomatic microhematuria. Int J Urol. 2000; 7(4):133-8.
17. Corrigan NT, Crooks J, Shand J. Are dedicated bladder films necessary as part of intravenous urography for hematuria? BJU Int. 2000; 85(7):806-10.
18. Avidor Y, Nadu A, Matzkin H. Clinical significance of gross hematuria and its evaluation in patients receiving anticoagulant and aspirin treatment. Urology. 2000; 55(1):22-4.
19. Khadra MH, Pickard RS, Charlton M, Powell PH, Neal DE. A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol. 2000; 163(2):524-7.
20. Singh GS, Rigsby DC. Asymptomatic microscopic hematuria in women: case series and brief review. Int Urogynecol J Pelvic Floor Dysfunct. 1999; 10(6):361-4.
21. Richards JR, Christman CA. Intravenous urography in the emergency department: when do we need it? Eur J Emerg Med. 1999; 6(2):129-33.
22. Yazaki T, Kamiyama Y, Tomomasa H, Shimizu H, Okano Y, Iiyama T, Iizuni T, Umeda T. Uretropyeloscopy in the diagnosis of patients with upper tract hematuria: an initial clinical study. Int J Urol. 1999; 6(5):219-25.
23. Yip SK, Peh WC, Tam PC, Li JH, Lam CH. Role of ultrasonography in screening for urological malignancies in patients presenting with painless haematuria. Ann Acad Med Singapore. 1999; 28(2):174-7.
24. Tan PK, Chang HC, Sitoh YY. Haematuria clinic—a preliminary audit and considerations for a one-stop assessment centre. Singapore Med J. 1998; 39(11):501-3.
25. Rockall AG, Newman-Sanders AP, al-Kutoubi MA. Vale JA. Haematuria. Postgrad Med J . 1997; 73(857):129-36.