Unexplained haematuria

(Section Editor: T.J. Rabelink)

Robert A. P. Koene

Department of Neprhology University Hospital Nijmegen Nijmegem The Netherlands

Patients with haematuria are usually referred to the urologist. When the haematuria is isolated, without other signs or symptoms, one should first try to distinguish between a glomerular and a non-glomerular source in order to decide which further investigations will be necessary. Although gross haematuria is more frequently the presenting symptom in non-glomerular haematuria, this is by no means a one hundred percent reliable, diagnostic criterion, since haematuria of glomerular origin can also present as macroscopic haematuria. To make the distinction, an individual with sufficient expertise in this field should examine the urinary sediment. In the University Hospital of Nijmegen we have therefore made an arrangement with the urology clinic to avoid unnecessary urological examinations in patients with glomerular haematuria. When a patient with unexplained, microscopic or macroscopic haematuria is referred to the urologist, the nephrologist is asked to examine the urinary sediment before invasive examinations are undertaken.

Patient A, whose urinary sediment is shown in Figure 1Go, is a 56-year-old male who had macroscopic haematuria without other symptoms. Semiquantitative examination of the urine showed 3+ protein. You are the nephrologist who is asked to examine the urinary sediment and to give advice to the urologist which further actions have to be taken.



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Fig. 1. Urinary sediment of patient A.

 
Question: Are the erythrocytes that you see in Figure 1Go of glomerular or non-glomerular origin?

Answer to question on the preceding page

The morphology of the erythrocytes in the urine can give information on the source of the bleeding [1–3]. Erythrocytes that have leaked through the glomerulus and have passed through the tubulus can become distorted during their passage along the nephron (dysmorphic or polymorphic erythrocytes). Erythrocytes originating from other sources in the urinary tract, for instance the bladder show much less signs of damage. They look more like the erythrocytes in the peripheral blood (isomorphic or monomorphic erythrocytes).

At first glance, the erythrocytes in Figure 1Go look dysmorphic. On closer examination it appears, however, that there are only two types of erythrocytes present: normal erythrocytes and crenated cells. The extent of the crenation of the cells differs and this gives the false impression that they are dysmorphic. The inexperienced examiner often makes such a mistake. One should keep in mind that more than two different forms of erythrocytes have to be present to allow for a diagnosis of dysmorphic erythrocytes, suggestive of a glomerular origin of the haematuria. Figure 2Go shows a different field in the same preparation where all erythrocytes are crenated. Here, the picture appears isomorphic which is consistent with a non-glomerular cause of the haematuria in this patient. Erythrocyte casts were not found on extensive screening. The proteinuria, that was also present, does not necessarily point to glomerular leakage of protein, but is commonly present in patients who have lost enough whole blood in their urine to cause gross haematuria. Your advice should be that a primarily urological investigation of the patient's haematuria is indicated.



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Fig. 2. A field with isomorphic, crenated cells in the same urinary sediment of patient A.

 
This example demonstrates that it is not always easy to distinguish between isomorphic and dysmorphic erythrocytes. A classical picture such as shown in Figure 3Go, is not always present. The microphotograph shows the typical polymorphism of the sediment, with a wide variety of differently shaped erythrocytes and erythrocyte fragments. Because of this difficulty in interpretation, it is important to regard the presence of dysmorphic erythrocytes mainly as a warning sign. It should lead to a meticulous search for erythrocyte casts in the sediment. Only the finding of erythrocyte casts can be considered convincing evidence that the haematuria has had its source in the glomerulus. In two different studies we found that erythrocyte casts can be found in about 85% of patients with glomerular haematuria [4,5]. In these studies two drops of the sediment were brought on a glass slide and covered with an 18x18 mm cover slip. The entire outer border of the cover slip was screened at low magnification (x100) for the presence of erythrocyte casts. Suspected structures were examined at higher magnification (x400). It is important to start screening the sediment at low power, since very often only a few erythrocyte casts are present and these are easily missed if the preparation is only examined at high power. This screening technique requires rapid back and forth switching of a low power (x10) and a high power (x40) objective. It is most easily performed with a normal light microscope at dimmed light with the condenser racked in a low position to increase the contrast. Performing the same procedure with a phase-contrast microscope is more cumbersome, because, at each switch of the objectives, the diaphragm in the condenser also has to be changed. Although it is widely claimed that phase contrast microscopy is better suited for the examination of the urinary sediment than normal light microscopy this contention has not been proven in a controlled study. In our experience, a simple light microscope is a very reliable tool for a proper examination of the urinary sediment.



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Fig. 3. Typical image of dysmorphic erythrocytes and an erythrocyte case in the urinary sediment of a patient with glomerular haematuria.

 

References

  1. Fairley KF, Birch DF. Haematuria: a simple method for identifying glomerular bleeding. Kidney Int 1982; 21: 1058
  2. Schramek P, Schuster FX, Georgopoulos M et al. Value of urinary erythrocyte morphology in assessment of symptomless microhaematuria. Lancet 1989; ii: 1316–1319
  3. Fogazzi GB, Passerini P, Ponticelli C, Ritz E. The urinary sediment. An integrated view. Masson, Milan: 1993
  4. Van der Snoek BE, Hoitsma AJ, van Weel C, Koene RAP. Dysmorfe erytrocyten in het urinesediment bij het onderscheiden van urologische en nefrologische oorzaken van hematurie. Ned T Geneeskd1994; 138: 721–726
  5. Van der Snoek BE, Koene RAP. Fixation of the urinary sediment. Lancet1997; 350: 933–934[ISI][Medline]