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. 2000 Jun 10;320(7249):1598.

Asymptomatic haematuria

All patients with haematuria should undergo cystoscopy

John Reynard 1
PMCID: PMC1127377  PMID: 10845979

Editor—Having just performed cystoscopy on a man of 36 who presented with bladder cancer five years ago, I am not reassured by Del Mar's so called evidence based survey of the likely diagnoses associated with occult haematuria.1

The quoted studies are likely to have missed cases of bladder cancer because not all patients underwent cystoscopy. Only 24 of 255 subjects in Ritchie et al's study underwent both upper tract imaging and cystoscopy.2 Among these, two cases of bladder cancer and one of bladder dysplasia (a premalignant condition) were found. The other 231 patients had not been adequately screened to exclude the presence of bladder cancer. There was no mention of long term follow up to confirm the absence of urological cancer in those who did not undergo initial cystoscopy. Similarly, not all of Hiatt and Ordonez's patients underwent a full urological evaluation,3 which prompts doubts about the accuracy of the performance statistics quoted in this paper.

Sultana et al performed cystoscopy and upper tract imaging in all patients referred over one year with microscopic haematuria.4 In those aged over 50, five bladder cancers and one renal cancer were diagnosed in 126 patients. More recently Khadra et al performed full urological evaluation of 982 patients with occult haematuria.5 Altogether 5% had bladder cancer, 4% stone disease, and 0.3% renal cancer.

Current urological training emphasises the importance of obtaining a midstream specimen of urine, upper tract imaging, and particularly cystoscopy in all patients who have haematuria, whether microscopic or macroscopic and whether persistent or not. Flexible cystoscopy can now be performed in minutes under local anaesthesia. I believe that there has to be a very good reason for not performing cystoscopy in patients with occult haematuria as this is likely to lead to missed diagnoses of bladder and renal cancer.

References

  • 1.Del Mar C. Asymptomatic haematuria . . . in the doctor. BMJ. 2000;320:165–166. doi: 10.1136/bmj.320.7228.165. . (15 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Ritchie CD, Bevan EA, Collier SJ. Importance of occult haematuria found at screening. BMJ. 1986;292:681–683. doi: 10.1136/bmj.292.6521.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Hiatt RA, Ordonez JD. Dipstick urinalysis screening, asymptomatic microhematuria, and subsequent urological cancers in a population-based sample. Cancer Epidemiol Biomarkers Prev. 1994;3:439–443. [PubMed] [Google Scholar]
  • 4.Sultana SR, Goodman CM, Byrne DJ, Baxby K. Microscopic haematuria: urological investigation using a standard protocol. Br J Urol. 1996;78:691–698. doi: 10.1046/j.1464-410x.1996.01975.x. [DOI] [PubMed] [Google Scholar]
  • 5.Khadra MH, Pickard RS, Charlton M, Powell PH, Neal DE. A prospective analysis of 1930 patients with hematuria to evaluate current diagnostic practice. J Urol. 2000;163:524–527. [PubMed] [Google Scholar]
BMJ. 2000 Jun 10;320(7249):1598.

Scottish guidelines are different from author's interpretation of best available evidence

James A D Finlayson 1

Editor—Del Mar's paper on finding an evidence based approach for the investigation of asymptomatic haematuria when he was both investigator and subject was fascinating.1-1 I was surprised that he makes no mention of the use that guidelines could have been. No doctor can know the details of every condition or have the time to conduct a literature search for every situation that faces us. We are instead encouraged to use guidelines written by experts who have presumably taken the trouble to look at the evidence and recommend an approach based on this.

I was therefore surprised that the relevant Scottish guidelines recommend an approach diametrically opposite to the one that Del Mar found on the basis of the available evidence. The guidelines of the Scottish Intercollegiate Guideline Network say that all people with asymptomatic haematuria require investigation including radiological imaging and cystourethroscopy.1-2 It is strange that one paper quoted by Del Mar as showing no need for investigation is interpreted in the Scottish guidelines as showing the value of investigation.1-3 It is worrying that the paper that Del Mar found most useful because it had a control group1-4 is not quoted by the Scottish guidelines.

In an interview in the BMJ, Lord Naren Patel—the new chairman of Scotland's Clinical Standards Board—seemed proud of the guidelines of the Scottish Intercollegiate Guideline Network and would intend to use them as something against which a clinical service could be measured.1-5 It is worrying, particularly in the present medicolegal and political climate, that guidelines do not seem to based on the best evidence available.

References

  • 1-1.Del Mar C. Asymptomatic haematuria . . . in the doctor. BMJ. 2000;320:165–166. doi: 10.1136/bmj.320.7228.165. . (15 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-2.Scottish Intercollegiate Guideline Network (SIGN) Investigation of asymptomatic microscopic haematuria in adults. Edinburgh: SIGN; 1997. . (SIGN publication No 17.) [Google Scholar]
  • 1-3.Ritchie CD, Bevan EA, Collier SJ. Importance of occult haematuria found at screening. BMJ. 1986;292:681–683. doi: 10.1136/bmj.292.6521.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-4.Hiatt RA, Ordonez JD. Dipstick urinalysis screening, asymptomatic microhematuria, and subsequent urological cancers in a population-based sample. Cancer Epidemiol Biomarkers Prev. 1994;3:439–443. [PubMed] [Google Scholar]
  • 1-5.Christie B. Scotland's way to guarantee quality. BMJ. 2000;320:78. doi: 10.1136/bmj.320.7227.78. . (8 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
BMJ. 2000 Jun 10;320(7249):1598.

Nephrological screening is important

Peter A Andrews 1

Editor—Del Mar's evidence based case report is unfortunate in reinforcing the all too common belief that haematuria is a surgical condition and that anything that is not cancerous is good.2-1

The author takes reassurance from two large studies suggesting that only a small proportion of patients presenting with microscopic haematuria will subsequently develop serious disease.2-2,2-3 Both studies, however, underestimate the importance of haematuria by not considering potential renal disease. In part, this is due to incomplete and short follow up, but urological bias is also a factor. Nephrological investigation of microscopic haematuria produces very different results. For example, Topham et al screened 165 patients with a mean age of 37.5 years and no adverse risk factors for renal disease and found important disease in 80; of these, 77 had abnormalities detected on renal biopsy, while only five had disease detected by urological investigation (three had dual disease).2-4

What, then, is the renal perspective? Firstly, microscopic haematuria below the age of 45 is highly unlikely to represent urological disease. Indeed, the United Kingdom Renal Association recommends that all patients aged under 45 presenting with microscopic (or macroscopic) haematuria should in the first instance be referred for a nephrological, rather than a urological, opinion.2-5 Nephrological screening will rarely miss important surgical disease, and patients in whom clinical suspicion remains can always be selectively referred. Secondly, long term follow up is indicated for all patients with microscopic haematuria to identify those with low grade glomerular disease such as IgA nephropathy, where up to 40% will require dialysis 20 years after presentation. This is particularly important since effective treatment—aggressive antihypertensive control and reduction of proteinuria and (possibly) immunosuppression—exists in such conditions.

Lastly, Del Mar's acceptance of diagnostic uncertainty does not always match that of our patients. In experienced hands renal biopsy is extremely safe, with a high diagnostic yield. A recent audit in my practice showed that over three fifths of counselled patients presenting with microscopic haematuria elected to have biopsy despite knowing that it rarely alters immediate management. Their reasons included the desire for a definite tissue diagnosis, exclusion of other conditions, avoidance of repeated cycles of urological investigation, and the possible advantage of a diagnosis of a benign condition as regards insurance loading and having children.

Del Mar might wish to reconsider a nephrological cause for his haematuria, and patients should be offered an informed choice when considering the investigation of the symptom.

References

  • 2-1.Del Mar C. Asymptomatic haematuria . . . in the doctor. BMJ. 2000;320:165–166. doi: 10.1136/bmj.320.7228.165. . (15 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2-2.Ritchie CD, Bevan EA, Collier SJ. Importance of occult haematuria found at screening. BMJ. 1986;292:681–683. doi: 10.1136/bmj.292.6521.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2-3.Hiatt RA, Ordonez JD. Dipstick urinalysis screening, asymptomatic microhematuria, and subsequent urological cancers in a population-based sample. Cancer Epidemiol Biomarkers Prev. 1994;3:439–443. [PubMed] [Google Scholar]
  • 2-4.Topham PS, Harper SJ, Furness PM, Harris KPG, Walls J, Feehally J. Glomerular disease as a cause of isolated microscopic haematuria. Q J Med. 1994;87:329–335. [PubMed] [Google Scholar]
  • 2-5.Renal Association. Treatment of adult patients with renal failure. Recommended standards and audit measures. 2nd ed. Suffolk: Lavenham Press; 1997. [Google Scholar]
BMJ. 2000 Jun 10;320(7249):1598.

Oxford Textbook of Medicine might have helped author

John G G Ledingham 1,2,3, David A Warrell 1,2,3, David Weatherall 1,2,3

Editor—Del Mar found neither Harrison's Principles of Internal Medicine nor Bailey and Love's Short Practice of Surgery helpful in determining the chance of a man in his 40s with persistent symptomless haematuria having a serious underlying disease.3-1 He fared no better with the Cochrane Library, but two papers of 230 dredged from Medline led him to pursue a policy of expectant observation, perhaps still with some misgivings.

Had he turned to the third edition of the Oxford Textbook of Medicine he would, we believe, have found the answer he sought more quickly.3-2 There he would have found that less than 2% of young people with haematuria without proteinuria have any significant disease (p 3145). He would also have found an algorithm showing different strategies of management and investigation depending on age over or under 45 (p 3147) and three references (p 3149) addressing the question he asks.3-3–3-5

We assume some error in the implication that 30 red cells per ml of urine constitutes haematuria, since such a figure is well within normal limits. Perhaps the figure was 30 cells per high power field or 30 cells per μl, although that last figure is again not too remarkable.

In the Editor's choice for the issue containing Del Mar's article the editor refers to the (his italics) textbook Harrison's Principles of Internal Medicine. Might he now consider that there are British textbooks to rival Harrison's?

Footnotes

The authors are the editors of the Oxford Textbook of Medicine, 3rd edition.

References

  • 3-1.Del Mar C. Asymptomatic haematuria . . . in the doctor. BMJ. 2000;320:165–166. doi: 10.1136/bmj.320.7228.165. . (15 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3-2.Weatherall DJ, Ledingham JGG, Warrell DA, editors. Oxford textbook of medicine. 3rd ed. Oxford: Oxford University Press; 1996. [Google Scholar]
  • 3-3.Britton JP, Dowell AC, Whelan PO. Dipstick haematuria and bladder cancer in men over 60: result of a community study. BMJ. 1989;299:1010–1012. doi: 10.1136/bmj.299.6706.1010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3-4.Froom P, Ribak J, Bombassat J. Significance of microhaematuria in young adults. BMJ. 1984;288:20–21. doi: 10.1136/bmj.288.6410.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3-5.Kincaid-Smith P. Haematuria and exercise-related haematuria. BMJ. 1982;285:1595–1597. doi: 10.1136/bmj.285.6355.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
BMJ. 2000 Jun 10;320(7249):1598.

Some people just have asymptomatic haematuria

Juliane Hentschel 1

Editor—I had a similar experience to Del Mar's,4-1 with haematuria, three years ago. I was an academic neonatologist in her 40s, interested in evidence based medicine. Using the keyword “EBM” I ran across Del Mar's article.

I found out that I had low grade persistent haematuria during compulsory medical examinations before starting work at new appointments. I was always told that I had a little blood in my urine, but in premenopausal women no one seems to take this seriously anyway. Then I had a bout of excruciating back pain with colic, which led to an investigation for renal stones in 1997. But no stones could be found, and my microscopic haematuria simply persisted after the attack. I then remembered that I had had an investigation for loin pain and stones some 10 years before, with no stones found then either, while I was working as a resident in the United States.

Since I seemed to have symptoms every now and then, and my father had died of renal failure after glomerulonephritis, I went to a nephrologist with several questions: What is this? How are the attacks of colic related? What can I do to avoid these attacks (they're extremely uncomfortable and refractory to usual painkillers)? He examined my urine, confirmed microscopic haematuria, and came up with the diagnosis of loin pain/haematuria syndrome—an obviously descriptive diagnosis.

I then did my searches with the above keywords and came up with the finding of “thin basement syndrome”—a concept that makes a lot of sense to me. Some people (at the lower end of normal for thickness of the glomerular basement membranes?) just seem to allow erythrocytes through to their urine, and that seems to be a genetic trait. I offered these thoughts to an academic nephrologist, but he wasn't interested.

In the end I came to similar conclusions to Del Mar's:

  • Some people (including academics) just have asymptomatic haematuria

  • If it stays the same it's not much to worry about

  • It's hard to stay away from investigations for renal calculi if you have back pain as well.

I am grateful to Del Mar for his thorough confirmation of the first point.

References

BMJ. 2000 Jun 10;320(7249):1598.

Author's reply

Chris Del Mar 1

Editor—The piece of evidence that was so compelling for me was the fact that having microscopic haematuria was no more predictive of unpleasant urological diagnoses than not having it.5-1 It suggests that the presence of invisible blood in the urine means I am not more likely to have urological cancer. Of course I am still at risk from this (as we all are), but no more than if I had normal urine.

“I am very sorry, but the test of your urine showed no microscopic blood; you have a small chance of having urological cancer, and we will need to start investigations. Some of these are expensive and somewhat unpleasant.” Surely no one would advocate this?

Neither am I inclined to submit myself for a renal biopsy. Andrews offers too little evidence in support of renal biopsy. My blood pressure is fine, and I have no proteinuria. Should either change I will act straight away. I would have to be convinced that I would benefit from immunosuppressive treatment at this early stage even if I had IgA nephropathy. The only alteration to my doing nothing is a slightly increased monitoring of my blood pressure and occasional testing of my urine for the development of increasing blood content or of proteinuria. The motto should be “don't do a test unless you will act on the result.”

The Oxford Textbook of Medicine is very good. But it does not refer to this compelling evidence either. In fact, the algorithm to which its editors direct attention suggests further investigation (imaging and long term follow up for the under 50s and, in addition, “look for carcinoma” in those aged 50 and over, which presumably means carry out cystoscopy). This is similar advice to that in competing texts. (Ledingham et al are correct in pointing out my error: the urine microscopy test showed 30 red cells per μl, not per ml as given in the article.)

Textbooks, like guidelines, may hide much of the process of making guidelines. This may be one reason why they are poorly implemented.5-2 It is as important to know the why of the guidelines as the what. Sometimes it is better to make the decision based directly on the information found. I choose to do nothing with this information. Others will choose differently. To allow patients and their doctors to make informed decisions together they must have the best information about the alternatives available and accessible to them, not merely cookbook recipes to be followed.

References

  • 5-1.Hiatt RA, Ordonez JD. Dipstick urinalysis screening, asymptomatic microhematuria, and subsequent urological cancers in a population-based sample. Cancer Epidemiol Biomarkers Prev. 1994;3:439–443. [PubMed] [Google Scholar]
  • 5-2.Cabana MD, Rand CS, Powe NR, Wu AW, Wilson MH, Abboud PA, et al. Why don't physicians follow clinical practice guidelines: a framework for improvement. JAMA. 1999;282:1458–1465. doi: 10.1001/jama.282.15.1458. [DOI] [PubMed] [Google Scholar]

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