Correspondence

Microscopic Hematuria

N Engl J Med 2003; 349:1292-1293September 25, 2003

Article

To the Editor:

In their Clinical Practice article on microscopic hematuria (June 5 issue),1 Cohen and Brown recommend a course of action that adheres to neither the recommendations of the American Academy of Family Physicians nor those of the American Urological Association.2 The diagnosis of microscopic hematuria, when it is not associated with a urinary tract infection or proteinuria, requires a referral to a urologist. Prospective, controlled trials of the standard urologic evaluation may alter current practice, but these trials have not yet been performed. Until data are available on which to base a firm recommendation, a change in the standard of care seems unwarranted.

Bladder cancer is characterized by intermittent rather than persistent hematuria,3,4 and tobacco use appears to account for only one third of bladder tumors in women in the United States. Thus, the history in this case, constructed to reassure the generalist that a conservative approach to the evaluation of microhematuria is appropriate, would be worrisome to urologists who recognize that further study of this patient is required.

David Chan, M.D.
Albert Ong, M.D.
Mark Schoenberg, M.D.
Johns Hopkins University, Baltimore, MD 21287
mschoenberg@jhmi.edu

4 References

1. 1

   Cohen RA, Brown RS. Microscopic hematuria. N Engl J Med 2003;348:2330-2338
   Full Text | Web of Science | Medline

2. 2

   Grossfeld GD, Litwin MS, Wolf JS Jr, et al. Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy. II. Patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up. Urology 2001;57:604-610
   CrossRef | Web of Science | Medline

3. 3

   Kretschmer HL. Haematuria: a clinical study based on 933 consecutive cases. Surg Gynecol Obstet 1925;40:683-686
   

4. 4

   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;137:919-922
   Web of Science | Medline

To the Editor:

As Cohen and Brown note, the presence of red cells should be confirmed by microscopic examination to rule out false hematuria. False hematuria can occur not only in the presence of free hemoglobin (hemoglobinuria or myoglobinuria), but also because of ascorbic acid (>5 mg per deciliter) or antiseptic povidone–iodine. In addition, a midstream urine collection should be considered, especially in women, since the first part of the urine stream is significantly more likely to contain red cells than the middle part of the stream, not only during the menstrual phase but also during the follicular and luteal phase of the menstrual cycle.1 Assessment of hypercalciuria, hyperuricosuria, or both — easily treatable causes of hematuria — is also important. Hypercalciuria, hyperuricosuria, or both are present in about 35 percent of cases of asymptomatic hematuria in the absence of visible stones, and treatment normalizes the secretion of calcium and uric acid in all patients and resolves the hematuria in 60 percent of cases.2 A 24-hour urine collection should be analyzed for calcium, uric acid, oxalates, and creatinine before one concludes that a patient has unexplained microscopic hematuria.

Malvinder S. Parmar, M.D.
Timmins and District Hospital, Timmins, ON P4N 8R1, Canada
atbeat@ntl.sympatico.ca

2 References

1. 1

   Morimoto M, Yanai H, Shukuya K, Chiba H, Kobayashi K, Matsuno K. Effects of midstream collection and the menstrual cycle on urine particles and dipstick urinalysis among healthy females. Clin Chem 2003;49:188-190
   CrossRef | Web of Science | Medline

2. 2

   Andres A, Praga M, Bello I, et al. Hematuria due to hypercalciuria and hyperuricosuria in adult patients. Kidney Int 1989;36:96-99
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Chan et al. advise that all patients with microscopic hematuria in the absence of a urinary tract infection or proteinuria be referred for urologic evaluation. First, this approach fails to consider the role of microscopical evaluation of urine, which identifies a glomerular source of microscopic hematuria in many patients, thereby rendering referral to a urologist unnecessary. Second, the literature suggests that there is a very low incidence of bladder cancer in men and women younger than 50 years of age who have only microscopic hematuria rather than gross hematuria, as Kretschmer reported in 1925.1 Accordingly, in this age group, we recommend referral to a urologist for cystoscopy only for those patients with microscopic hematuria who have either abnormal findings on cytologic analysis of urine or risk factors for bladder cancer. To do otherwise would expose many patients to the risks, discomfort, and expense of this invasive procedure unnecessarily, without data showing that it is associated with a beneficial outcome. On this point, we are at variance with the recommendation of the American Urological Association, accepted by the American Academy of Family Physicians, that urologic evaluation with cystoscopy should be the “standard of care,” as advised by Chan et al.

We agree with Dr. Parmar that if a dipstick test of urine is positive for heme, the presence of red cells must be confirmed by microscopical examination. Other than myoglobinuria and hemoglobinuria, we did not include uncommon conditions associated with false positive dipstick tests for heme that would not alter the approach that we outlined.

We concur that hypercalciuria, hyperuricosuria, or both are possible causes of unexplained microscopic hematuria, as listed in Table 1 of our article. However, it may be misleading to state that these conditions cause 35 percent of cases of unexplained hematuria in adults and that 60 percent of such cases resolve with treatment. This claim is based on a single series of 37 adults in Spain, 18 of whom had episodic gross hematuria. Caution must be exercised in generalizing these findings to all adults with unexplained microscopic hematuria. Red-cell counts may be lower in midstream urine samples than in initial-stream samples in young female patients during some phases of the menstrual cycle. However, since the dipsticks in the study cited by Dr. Parmar were negative for heme and did not differ according to the part of the urine stream,2 the pertinence of this factor to the clinical evaluation remains to be shown.

Robert A. Cohen, M.D.
Robert S. Brown, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215
rcohen@bidmc.harvard.edu

2 References

1. 1

   Kretschmer HL. Haematuria: a clinical study based on 933 consecutive cases. Surg Gynecol Obstet 1925;40:683-686
   

2. 2

   Morimoto M, Yanai H, Shukuya K, Chiba H, Kobayashi K, Matsuno K. Effects of midstream collection and the menstrual cycle on urine particles and dipstick analysis among healthy females. Clin Chem 2003;49:188-190
   CrossRef | Web of Science | Medline