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THE ROL OF ELECTRON MICROSCOPY IN THE ROUTINE STUDY OF NATIVE RENAL BIOPSIES

The justification for the routine use of electronic microscopy (EM) in the study of renal biopsies comes from studies made, most of them, in the sixties and principles of the seventies (1,2,3,4). Siegel et al (1) found that EM permitted to arrive at a substantially different diagnosis to the light microscopy (LM) diagnosis in 11% of cases, and Olsen et al (2) report this percentage being 13%. Muehrcke et al (3) found that EM significantly contributed to the diagnosis only in 6% of the cases; they concluded that EM it is not necessarily a routine procedure in the study of renal biopsies and that it is a luxury more than a necessity. All the previous studies were made without the aid of the immunofluorescence (IF). With the introduction of the routine use of the IF in the renal biopsy diagnosis, in the seventies, most of primary glomerulopathies can be well diagnosed, with accuracy, with LM and IF.

Three important changes have happened from the sixties with respect to the use of EM in the diagnosis of renal biopsies. 1.) The economic conditions of the medical practice have changed dramatically and there is a constant pressure to reduce the number of studies of high cost. EM is an expensive procedure, with a value approximately equivalent to LM plus IF study. 2.) IF in renal biopsies is now used in generalized form, in opposition to the habitual practice in the sixties, at that time the use of EM was considered in more detail and an almost obligatory technique in renal pathology. 3.) There are glomerular diseases, or variants of them, recently describes, several which need the ultrastructural study for their correct classification (5,6,7).

In most of the renal diseases, with an adequate tissue sample, correctly processed, with optimal stains, and optimal IF it is possible to arrive to the precise diagnosis without EM.

Some of the primary glomerulopathies necessarily require EM: thin glomerular basement membrane disease, Alport syndrome, fibrillary and/or immunotactoid glomerulonephritis, and minimal change disease. In addition, it is useful, although not essential, in the diagnosis of any other glomerulopathy.


By frequency, minimal change disease is the glomerulopathy that more requires EM, since it is, by definition, an ultrastructural diagnosis. Nevertheless, in a suitable clinical context, with a representative sample of renal cortex, and adequate stains and IF it is possible to make a reliable diagnosis in most of the cases.

There are renal biopsies in which the IF gives doubtful results and the findings in the LM do not allow us to reach a final diagnoses; these cases require aid of the electron microscope and for them we must have reserved renal tissue for the ultrastructural study.

Dr Mark Haas recommends that if the ultrastructural study cannot be made routinely in all the biopsies of native kidney, it is wise to preserve the material in such a fashion that ultimately electron microscopy is still possible. This preserved tissue would serve to make the ultrastructural study if has not been possible to arrive at a definitive diagnosis with LM and IF (5,8). The same view is expressed by Drs. Amann and Haas in a recent article: What you should know about the work-up of a renal biopsy. Nephrol Dial Transplant. 2006;21:1157-61. [PubMed link] [Free full text].

In conclusion, electronic microscopy is a technique that continues being very useful on daily renal practice. Ideally all the native kidney biopsies and some kidney allograft biopsies must have EM, principally at university and investigation centers where is very important to know additional details to the basic or main diagnosis and to corroborate with the ultrastructure the diagnosis made with the LM and IF. On daily practice of nephropathology, and with aims of diagnosis and treatment of patients, without considering the investigation nor teaching, EM can be considered as an additional, complementary study of the other two techniques, and EM would be made in suspicious cases of thin glomerular basement membrane disease, cases in which has not been possible to confirm the diagnosis of minimum changes disease (by a doubtful result in the IF), suspicious cases of immunotactoid and/or fibrillary glomerulopathy, and cases of any other glomerulopathy in which, for any reason, the pathologist has not been able to arrive at a precise diagnosis with LM and IF. Therefore, ideally, we always would keep tissue adequately handled for EM and to carry out this study according to the results of the LM and IF, and always based on the pathologist’s concept.


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References
1. Siegel NJ, Spargo BH, Kashgarian M, Hayslett JP. An evaluation of routine electron microscopy in the examination of renal biopsies. Nephron 10: 209-215, 1973
2. Olsen S, Bohman SO, Hestbech J, Gundersen HJG, Petersen VP, Deguchi N, Maunsbach AB. Ultrastructural lesions in light-microscopically defined types of glomerulonephritis. Acta Pathol Microbiol Inmunol Scand Sect A 91: 53-63, 1983
3. Muehrcke RC, Mandal AK, Gotoff SP, Isaacs EW, Volini FI. The clinical value of electron microscopy in renal disease. Arch Intern Med 124: 170-176, 1969
4. Tighe JR, Jones NE. The diagnostic value of routine electron microscopy of renal biopsies. Proc R Soc Med 63: 475-477, 1970
5. Haas M. A reevaluation of routine electron microscopy in the examination of native renal biopsies. J Am Soc Nephrol 8: 70-76, 1997. (PubMed link)
6. Pearson JM, McWilliam LJ, Coyne JD, Curry A. Value of electron microscopy in diagnosis of renal disease. J Clin Pathol 47: 126-128, 1994. (PubMed link / Free full text)
7. Furness PN, Boyd S. Electron microscopy and immunocytochemistry in the assessment of renal biopsy specimens: actual and optimal practice. J Clin Pathol 49: 233-237, 1996. (PubMed link / Free full text)
8. Sementili A, Moura LA, Franco MF. The role of electron microscopy for the diagnosis of glomerulopathies. Sao Paulo Medical J 122; 104-109, 2004. (PubMed link / Free full text)

Another recent bibliography

Amann K, Haas CS. What you should know about the work-up of a renal biopsy. Nephrol Dial Transplant. 2006 May;21:1157-61. [PubMed link] [Free full text]

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