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Electron microscopy (EM) is an essential tool for diagnostic renal biopsy in certain cases of renal disease. For instance, it has been in use for decades for pathological diagnosis of glomerular disease and its value as a significant diagnostic tool is receiving emphasis. However, its limitations in other areas of pathological diagnosis like tumor pathology and its cost has seen the electron microscopy receive its own share of back lashing (Amann and Haas 2).
There are some cases of renal conditions which need more insightful studies before a treatment procedure is arrived at. For a long time, light microscopy has been used to diagnose renal pathology and with the collaboration of immunofluorescence findings, most renal disease can be diagnosed accurately and reliably. However, certain types of glomerular disease are essentially diagnosed by electron microscopy and in other cases renal studies by light microscopy and immunofluorescence findings require the confirmation of electron microscopy.
Most studies carried out to find out the need for routine use of electron microscopy in diagnosis of renal pathology were done in the sixties. In the course of time, the uses of electron microscopy in diagnosis of renal biopsies have since changed in at least three ways;
the cost implications of the medical practice have shifted dramatically due to the pressure to minimize the number of high cost studies. Electron microscopy is an expensive medical practice which is equivalent to the light microscopy and immunofluorescence studies combined together,
contrary to the habitual diagnosis in the sixties when the application of electron microscopy was considered an almost obligatory diagnostic technique in renal biopsy, immunofluorescence is now employed in generalized form, and
several variants of recently described glomerular diseases need ultrastructural studies for their correct classification.
Most renal diseases can be precisely diagnosed without electron microscopy. However, this requires an adequate and correctly processed tissue sample with optimal stains and optimal immunofluorescence.
“Thin glomerular basement membrane disease, minimal change disease, fibrillary and immunotactoid glomerulonephritis and Alport syndrome are some of the glomerular diseases which necessarily require electron microscopy for precise diagnosis” (Amann and Haas 3). Additionally, it has proved to be helpful in the diagnosis of other glomerular diseases even though it’s not essential in such cases but helpful to the light microscopy and immunofluorescence findings.
“Minimal change glomerular disease requires an ultrastructural diagnosis and it requires the electron microscopy more than any other glomerulopathy” (Pearson et al 2). Immunofluorescence gives doubtful diagnosis in some renal biopsies and the findings of light microscopy alone cannot help arrive at final diagnoses. In this case, an ultrastructural study using an electron microscope is used.
Numerous studies have been carried out to investigate the value of electron microscopy in diagnosis of renal pathology whereby electron microscopy was used alongside light microscopy and fluorescence findings. The result findings have been well published by various authors to illustrate how electron microscopy is used in renal pathology diagnosis.
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According to studies performed in 1969, a mere 6% of the 179 cases evaluated showed that electron microscopy contributed significantly to the diagnosis and they thus deduced that this tool should not be used as routine procedure and it is unnecessarily expensive. Tighe and Jones agree with this observation that in addition to the cost of electron microscopy, it is also time-consuming as they found out after investigating a series of 100 cases. However, they observed that routine diagnostic electron microscopy is very important in differential diagnosis of nephritic syndrome (Amann and Haas 5).
The importance of routine electron microscopy in differential diagnosis of nephritic syndrome was evaluated by Ben-Bassat et al in 37 cases. They found that routine electron microscopy played an important role in providing accurate diagnosis of minimal change disease for treatment and prognosis. This work was supplemented by findings from studies by Pearson whereby he investigated the contribution of electron microscopy and immunofluorescence to diagnosis of glomerulonephritis. They observed that one or both electron microscopy and immunofluorescence and electron microscopy should supplement light microscopy. Spargo concluded that routine electron microscopy should be used whenever a renal biopsy is to be evaluated following evaluation of the tool in diagnosis of glomerular disease.
The role of routine electron microscopy in diagnosis and management of patient was investigated using 213 renal biopsy specimens. They found although electron microscopy permitted to arrive at substantially different diagnosis to the light microscopy diagnosis in 11% of cases investigated, it was important in confirmation of the diagnosis by light microscopy and in management. In another study by Olsen et al, they found the figure of different diagnosis to light microscopy to be 13%. Some researchers were able to demonstrate that electron microscopy can make a significant contribution to the precise diagnosis of glomerular disease since it allowed for the detection of immune deposits.
The role of electron microscopy in renal biopsy was investigated and found out that this diagnostic tool provided additional information in some cases about the glomerulonephritis. It was upon this observation they concluded that electron microscopy should be used on routine basis on cases suspected to be glomerulonephritis.
In the study conducted by Pearson, McWilliam and Coyne (4) on the routine use of electron microscopy, in conjunction with the light microscopic and immunofluorescence findings they found out that electron microscopy had an essential role in 25% out of the 88 cases investigated and proved to be helpful in half of these cases. The figures were generally consistent with those found by other researchers. This study is much more comprehensive compared to the earlier work done by others as it included immunofluorescence findings in the assessment. When used in conjunction with light microscopy and immunofluorescence findings, electron microscopy can provide more accurate diagnosis of glomerulonephritis.
Electron microscopy has been found to be most useful in minimal change nephropathy and in differential diagnosis. Except in possibility of very early membranous disease, early amyloid, or abnormal membrane in otherwise normal looking gromeruli through light microscopy, electron microscopy was found to be essential. In addition, it is essential in excluding immune deposits in which case the final diagnosis by electron microscopy is clinically very important. Electron microscopy is an important component of diagnosis in cases of nephrosis and proteinuria. It is particularly helpful in detecting the location and nature of deposits/ abnormal matrix and is complementary to confirming the final diagnosis.
As mentioned before, electron microscopy is much more sensitive and specific in certain cases. For instance, studies carried out by medical researchers in 1994 clearly indicate the specificity and sensitivity in picking up of membranous glomerulonephritis by electron microscopy more than immunofluorescence and light microscopy. Quite often electron microscopy has been used for correct diagnosis of minimal change glomerulonephritis which is difficult to investigate using light microscopy and immunofluorescence techniques alone.
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Electron microscopy is particularly essential in diagnosis of patients presented with nephritic syndrome with proteinuria. Depending on light microscopic and immunofluorescence techniques may not provide the correct diagnosis. Consequently, a wrong treatment scheme may be administered. For example, other diagnostic tools may not be able to reveal the subepithelial electron deposits of membranous glomerulonephritis in the biopsy or the observation may not be definitive as is the case with scanty deposits of IgG visible in immunofluorescence study. An electron microscopy will however provide precise information and help in the correct treatment of the specific problem.
In addition to the diagnosis of membranous glomerulonephritis, there are many other conditions which need electron microscopy examinations. For example, patients suffering from thin basement membrane syndrome need electron microscopy (Pradhanl and Kakkarl 1). Thin basement membrane syndrome is known to present with persistent with haematuria. It has been demonstrated that electron microscopy can distinguish between membranous glomerulonephritis and mesangio-capillary glomerulonephritis. The former in its late stage shows considerable basement membrane thickening which can easily be confused with mesangio-capillary glomerulonephritis (Pradhanl and Kakkarl 7).
The ability of electron microscopy technique to provide precise renal diagnosis has found wide applications even in postmortem studies. Ideally, it is a very useful tool for deciding even the most complicated cases of renal disease or rare conditions. This was illustrated in 1991 in a study where an electron microscopy study provided a precise diagnosis of rare but specific multiple osteolytic lesions in a woman with adult Fanconi syndrome which was otherwise impossible with the light microscopy and immunofluorescence findings. In their other studies they also found out (Pearson et al1).
In similar studies, it was shown that properly prepared and stored sample renal tissue for electron microscopy can be used at a later date for subsequent studies. This is most ideal for postmortem studies to help in determining the exact cause of death in circumstances when the light microscopic investigations and immunofluorescence findings can not point rare or unknown conditions. The fact that electron microscopy studies are possible after long periods and its ability to diagnose even the rarest conditions highlights its sensitivity for renal pathology studies as opposed to light microscopy and immunofluorescence findings.
Electron microscopy is an important diagnostic technique which is very useful in everyday renal biopsy practice. In principle all native renal biopsies and some renal allograft biopsies should undergo electron microscopy in addition to the light microscopy and immunofluorescence findings. This is particularly important in institutions where additional information to the basic/ main renal diagnosis is needed in order to confirm the ultrastructure diagnosis made by the light microscopy and immunofluorescence findings.
The discussion going on is on whether electron microscopy should be used on routinely in the renal pathology diagnosis. As most studies have shown, electron microscopy is essential and also helpful in some cases of renal biopsies and the choice of use of the technique is informed by the need. The biggest limitation of the technique is the time taken to perform a single diagnosis with electron microscopy.
The pathologist has to carry out the study for several hours and this may not be appropriate in time-sensitive cases. The cost of the technique is also another factor because it is very expensive (it is as expensive as light microscopy and immunofluorescence findings combined). Therefore its use may not be widespread but rather confined to a few institutions which can afford the cost of an electron microscope (Darouich and Goucha 49).
Clinically, electron microscopy is used as an additional and complementary study of the light microscopy and immunofluorescence. It is especially essential in investigating cases suspected to be thin glomerular basement membrane disease, confirmation of the diagnosis of minimum chance renal diseases where it is not possible with the other techniques. Electron microscopy is also important in diagnosis of suspicious cases of fibrillary and immunotactoid glomerular diseases and other cases of glomerular diseases whereby the light microscopic and immunofluorescence investigations can not help the pathologist reach a precise diagnosis (Pearson et al 3).
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For this reason, it is recommended that adequate tissue should be kept whenever renal biopsy is carried out for electron microscopy should need arise after results of the light microscopy and immunofluorescence findings (Darouich and Goucha 61). Properly prepared and stored tissue can be used electron microscopy after a relatively long time.
The benefits of electron microscopy cannot be gainsaid. Even though they are commonly used in higher institutions, they are greatly significant both in pathology research as well as clinical applications. There clinical applications are most important as they help in making decision on specific treatment procedures and their absence in clinical studies may lead to incorrect treatments. Routine application of electron microscopy in renal pathology studies can only be hindered by the cost of an electron microscope and duration of the diagnostic technique as it takes the pathologist long hours to complete the study with electron microscopy.
Amann, Kerstin, and Haas, Christian. “Nephrology Dialysis Transplantation: What you should know about the work-up of a renal biopsy.” Oxford Journals 5(2005):1-5.
Ben-Bassat M, Stark H, Robson M, and Rosenfield, J. “Value Of Routine Electron Microscopy in the Differential Diagnosis of the Nephrotic Syndrome.” Pathol Microbiol 41 (2006): 26-40.
Darouich, Sihem and Goucha, Louzir. “Ultrastructural Pathology: Value of Electron Microscopy in the Diagnosis of Glomerular Diseases.” Informal Healthcare 34 (2010): 49-61.
Pearson, J M, McWilliams, L J and Coyne, J D.” Value of Electron Microscopy in Diagnosis of Renal Disease.” Acta Pathol Microbiol Scand 2 (2007): 1-3.
Pradhanl, Dinesh and Kakkarl, Nandita. “Sub-Typing Of Renal Cell Tumours; Contribution of Ancillary Techniques.” Diagnostic Pathology 21 (2009): 1-7.