Microscopic haematuriaBMJ 1994; 309 doi: https://doi.org/10.1136/bmj.309.6947.70 (Published 09 July 1994) Cite this as: BMJ 1994;309:70
- Fritz H Schroder
Gross haematuria is obvious to the patient and is usually followed up, appropriately, by a complete urological work up. The much commoner microscopic haematuria, however, may not always receive the attention that it deserves. Dealing with this symptom adequately in the general practitioner's surgery requires a substantial body of knowledge. Recent developments warrant a re-examination of this topic.
Microscopic haematuria is rare before the age of 50 (occurring in fewer than one in 100 people of this age); after 50 the prevalence rises sharply and varies from 2% to 18% 1 2 (with some of this variation explained by different definitions). The commonly used dipstick test gives a yes or no answer to the question of whether microscopic haematuria is present and semiquantitative information at the same time. Comparing its results with those of standard microscopic evaluation of urinary sediments, one representative study found a sensitivity of 100% and a specificity of 60%.3 The relatively high frequency of false positive results of dipstick tests may be due to the technique's detection of normal numbers of red cells (1-2×1012/1 urine). The consensus is that if the result of a dipstick test is positive then the urinary sediment should be examined; if the result of a dipstick test is negative no further investigation is needed.
The figure gives an algorithm of recommended diagnostic tests for patients with haematuria. Several explanations exist for some of the variations in the prevalence of microscopic haematuria in different populations. A dipstick test may yield a positive result in the very concentrated early morning urine whereas it may give a negative result during the day after fluid intake. Several other artefacts, especially the contamination of urine with menstrual blood or sexual trauma in men and women, must be considered. Laville et al evaluated risk factors in 8200 workers in the metallurgical and chemical industries and found that the following conditions conferred a significantly increased relative risk of microscopic haematuria: age above 40, female sex, arterial hypertension, smoking, the use of non-steroidal anti-inflammatory drugs, a history of urological disease, and employment in the chemical industry.4 It may be specific to this population group that, of 222 subjects studies, 90.5% had glomerular haematuria as defined by the presence of dysmorphic erythrocytes.
Confirm, investigate, retest if negative
A “normal” upper limit for microscopic haematuria has yet to be agreed. Recommendations vary between 2 and 5 erythrocytes/high power field. Messing et al found no correlation between the number of erythrocytes and the number of times haematuria was present and the seriousness of its possible cause.2 Mariani et al found that in none of 1000 consecutive patients with a serious underlying cause for their haematuria were fewer than 3 erythrocytes present per high power field. The recommendation is that any haematuria should be re-evaluated once or twice for confirmation. Once microscopic haematuria has been reliably shown the patient should be investigated unless the finding can be explained. If the results of investigations are negative, testing for haematuria should be repeated twice at intervals of six months. Occult cancer will show within a year.
A diagnosis of haematuria, whether gross or microscopic, requires extensive investigation to exclude any serious underlying condition. Treatment with anticoagulants is not an excuse to avoid further investigation—such treatment more often provokes haematuria from preexisting lesions than causes it de novo.
The chance of detecting a nephrological or urological condition varies strongly with the risk factors discussed above. In men and women over 50, pathological explanations will be found for haematuria in up to four fifths of cases. Further investigations for haematuria uncover life threatening conditions in between 12% and 34% of patients. The risk of such conditions is lower in younger patients and is lower in women than men.
Several examinations of the urinary sediment should follow a positive result of a dipstick test. If white cells are present then urinary culture is mandatory. Recommended laboratory studies should include cytological examination of urine. This should be followed by ultrasonographic examination of the kidneys and bladder—a recommendation that is based on a recent decision analysis by Corwin and Silverstein.5 Their analysis clearly showed that ultrasonography is as sensitive as intravenous urography and is more cost effective. Unfortunately, the accuracy of ultrasonography depends very much on the operator so unless a high quality examination can be guaranteed intravenous urography may still be the study of choice. A plain film of the abdomen should also be obtained, mainly to rule out urinary calculi.
Glomerular or non-glomerular?
If no renal explanation is found cystoscopy should follow. The procedure can be performed with a flexible instrument in outpatients and is much less traumatic than previously.
If no explanation for the haematuria is found with the steps outlined so far, a phase contrast or Coulter counter analysis of the excreted erythrocytes should be carried out to determine whether the haematuria is glomerular or non-glomerular. (Erythrocytes that have passed through the glomerular membrane are dysmorphic and smaller than normal erythrocytes.)
Phase contrast microscopy and Coulter counter analysis detect such cells very accurately.6 Dysmorphic erythrocytes, especially if associated with substantial proteinuria, suggest a renal origin for the haematuria. The work up should then include a more extensive history and laboratory studies (which may include renal biopsy). If the haematuria is not of glomerular origin then intravenous urography may be needed. If a definite diagnosis cannot be made investigations should be repeated whenever gross haematuria occurs or within four to six months. Renal angiography, computed tomography, or biopsy is indicated only under very specific circumstances.
The commonest causes of glomerular haematuria are IgA nephropathy followed by the other glomerulonephritides. Among 1000 patients with haematuria the common causes of non-glomerular haematuria were inflammatory conditions of the urethra and prostate (usually trigonitis) (377 cases), benign prostatic hyperplasia (165), cystitis (73), transitional carcinoma of the bladder (65), and stones in the renal pelvis or ureter (34).1 Altogether 80 patients had some form of cancer. In a screening study of men over 50, pathological conditions were found in 31 of 44 men who had haematuria at least once on serial testing. One third of the 44 men had either cancer of the urinary tract or other conditions requiring immediate treatment.2
Every case of microscopic haematuria should therefore be evaluated. The simultaneous use of anticoagulants is no longer a satisfactory explanation. Separating glomerular from non-glomerular haematuria with Coulter counter or phase contrast analysis of the urinary sediment can facilitate diagnosis, and these analyses should be used often. If the results of a single work up are inconclusive and microscopic haematuria persists then the diagnostic tests should be repeated in due course.