Unexplained haematuria

Giovanni B Fogazzi

Divisione di Nefrologia e Dialisi, Ospedale Maggiore, IRCCS, Via Commenda 15-20122 Milano, Italy

Sir,

I read with interest the Nephroquiz for the Beginner by Dr R. A. P. Koene about unexplained haematuria [1]. I do agree with Dr Koene about the utility of the analysis of urinary red cell morphology, the uncertainty which in some cases this analysis entails, and the valuable information obtained by the search of erythrocyte casts in patients with haematuria of unknown origin. However, some statements of Dr Koene's are, in my opinion, debatable.

First, the criterion that the presence of ‘more than two different forms of erythrocytes’ allows a diagnosis of dysmorphic erythrocytes, is only one of several criteria reported in the literature. For instance, other investigators consider a haematuria as glomerular when more than three morphological types of erythrocytes are present [2,3], or when there are more than 80% dysmorphic erythrocytes [4].

In addition, Dr Koene did not mention acanthocytes or G1 cells, which are a subtype of dysmorphic erythrocytes whose distinguishing feature is the presence of one or more blebs protruding from a ring-formed red cell. It has been shown that when these erythrocytes represent at least 5% of total urinary red cells, they indicate glomerular bleeding with a 52–100% sensitivity and 98–100% specificity [5,6]. Since acanthocytes/G1 cells are easily identifiable, I think that a useful suggestion for beginners should have been that these cells should also be looked for.

Second, I find it difficult to accept the statement that the use of ‘a phase contrast microscope is cumbersome’. With the average instrument the switch of the diaphragm of the condenser to the corresponding objective is extremely simple and is done in less than 1 s. Moreover, compared with traditional microscopy, phase contrast provides a better identification of all the elements of the urinary sediment (Figure 1Go), including erythrocytes. A comparison between phase contrast and bright field in evaluating urinary red cells has in fact been performed by Dinda and co-workers [6]. In 82 patients with a glomerular disease, phase contrast microscopy showed significantly more dysmorphic erythrocytes and G1 cells than bright field microscopy performed on supravitally stained urine. Phase contrast microscopy was also better at identifying a glomerular haematuria based on the search of ‘dysmorphic’ erythrocytes (sensitivity 90% vs 82%, specificity 100% with both methods).



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Fig. 1 The striking difference between phase contrast (left) and bright field microscopy in showing casts, cells and morphological details (x400) (from Fogazzi GB, Ponticelli C, Ritz E. The urinary sediment. An integrated view. Second edition. Milano: Masson 1999. Reproduced with permission).

 
Equipping a microscope with a phase contrast condenser and objective certainly entails an extra cost. However, this is usually affordable in Western countries, and after the purchase no additional expenses are required. In my 16-year experience, started incidentally with a bright field microscope, phase contrast represents the best instrument for urine in all respects, including the training of a beginner.

References

  1. Koene RAP. Unexplained haematuria. Nephrol Dial Transplant1999; 14: 2025–2027[Free Full Text]
  2. Loh EH, Keng VW, Ward PB. Blood cells and red cell morphology in the urine of healthy children. Clin Nephrol1990; 34: 185–187[ISI][Medline]
  3. Crompton CH, Ward PB, Hewitt IK. The use of urinary red cell morphology to determine the source of hematuria in children. Clin Nephrol1993; 39: 44–49[ISI][Medline]
  4. Fasset RG, Horgan BA, Mathew TH. Detection of glomerular bleeding by phase-contrast microscopy. Lancet1982; i: 1432–1434
  5. Köhler H, Wandel E, Brunck B. Acanthocyturia—a characteristic marker for glomerular bleeding. Kidney Int1991; 40: 115–120[ISI][Medline]
  6. Dinda AK, Saxena S, Guleria S et al. Diagnosis of glomerular haematuria: role of dysmorphic red cell, G1 cell and bright field microscopy. Scand J Clin Lab Invest1997; 57: 203–208[ISI][Medline]

 

Reply

Robert A. P. Koene

Department of Nephrology, University Hospital Nijmegen, Nijmegen, The Netherlands

Sir,

The comment of Dr Fogazzi on the significance of acanthocytes is well taken. I agree with him that the acanthocyte is highly specific for glomerular haematuria. For that reason this subtype of dysmorphic erythrocytes should have been discussed in a contribution for the novice. In my discussion of the case I originally left out the acanthocyte, not only because I did not intend to discuss the characteristics of all types of dysmorphic erythrocytes in detail, but also because these cells are generally not abundantly present in the urinary sediment. In the large study of Köhler et al. [1], acanthocyturia (>=5%) was seen in only 75 of 143 patients with proven glomerulonephritis (sensitivity 52%). Because of this low sensitivity, acanthocyturia is not a very useful parameter in the routine screening of unexplained haematuria. Although the sensitivity may increase by performing repeated examinations, it seems more efficient to screen for erythrocyte casts, since the detection of a single typical erythrocyte cast in the sediment of an individual with unexplained haematuria provides strong proof for glomerular leakage of erythrocytes. As I mentioned in my Nephroquiz contribution, we have shown that the sensitivity of a single screening is as high as 85%.

Not unexpectedly, Dr Fogazzi has a different view on the use of phase contrast microscopy. Indeed, the figure he provides (Figure 1) demonstrates that phase contrast can give more attractive images than bright field microscopy. However, I was somewhat confused by his mentioning of the study of Dinda and co-workers [2] as a support for the use of phase contrast microscopy. The authors of this report actually concluded that: ‘the ordinary bright field microscope can be used for the diagnosis of glomerular haematuria with an efficiency similar to that of a phase contrast microscope’. This conclusion was based on their finding that, at the cut-off points chosen, the diagnostic sensitivity and specificity of both methods were not different. However, I hesitated to use these results to support my statement, because the investigators used not only unstained but also supravitally stained sediments for bright field microscopy. It is not clear whether their results were based on stained or unstained sediments or on a mixture of both examination techniques. Supravital staining is not a very attractive approach to the examination of the urinary sediment, since it almost invariably causes extensive and troublesome background staining.

In conclusion, I see no good reasons to withdraw my original statement that the superiority of phase contrast microscopy in the examination of the unstained sediment has never been demonstrated in a controlled study. To underscore my plea for the use of bright field microscopy, I have added a colour photograph of dysmorphic erythrocytes of a patient with proven glomerulonephritis as seen in bright field or phase contrast microscopy (Figure 2Go). Bright field microscopy is more widely accessible in the laboratory, it is easier to use, and it has advantages for the screening of erythrocyte casts.



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Fig. 2. Dysmorphic erythrocytes in the unstained urinary sediment of a patient with biopsy-proven glomerulonephritis as seen with bright-field (upper panel) and phase contrast microscopy (lower panel).

 

References

  1. Köhler H, Wandel E, Brunck B. Acanthocyturia—a characteristic marker for glomerular bleeding. Kidney Int1991; 40: 115–120[ISI][Medline]
  2. Dinda AK, Saxena S, Guleria S et al. Diagnosis of glomerular haematuria: role of dysmorphic red cell, G1 cell and bright-field microscopy. Scand J Clin Lab Invest1997; 57: 203–208[ISI][Medline]




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