Value of Electron Microscopy in the Diagnosis of Childhood Nephrotic Syndrome

The value of the ultrastructural study of the renal biopsy was investigated in a series of pediatric patients with nephrotic syndrome. Forty-eight cases of renal biopsies with clinical data were reviewed and divided into diagnostic groups. The contribution of electron microscopy to the final diagnosis was graded as essential — diagnosis could not be reached without it; supportive — it increased the level of confidence in the final diagnosis; and noncontributory. In this series of renal biopsies from 48 children with nephrotic syndrome resistant or nonresponsive to therapy, the mostfrequent diagnosis was minimal change disease, present in 42%of the patients. The contribution of the electron microscopic study to the final diagnosis was essential in 73%of the series, and was supportive in a further 27%.Therefore, it is concluded that the ultrastructural study was an essential component in the study of the renal biopsy in children with nephrotic syndrome, suggesting that electron microscopy needs to continue to be performed for all these patients.     

Value of electron microscopy in the diagnosis of childhood nephrotic syndrome

The value of the ultrastructural study of the renal biopsy was investigated in a series of pediatric patients with nephrotic syndrome. Forty-eight cases of renal biopsies with clinical data were reviewed and divided into diagnostic groups. The contribution of electron microscopy to the final diagnosis was graded as essential-diagnosis could not be reached without it; supportive-it increased the level of confidence in the final diagnosis; and noncontributory. In this series of renal biopsies from 48 children with nephrotic syndrome resistant or nonresponsive to therapy, the most frequent diagnosis was minimal change disease, present in 42% of the patients. The contribution of the electron microscopic study to the final diagnosis was essential in 73% of the series, and was supportive in a further 27%. Therefore, it is concluded that the ultrastructural study was an essential component in the study of the renal biopsy in children with nephrotic syndrome, suggesting that electron microscopy needs to continue to be performed for all these patients.     

Value of Electron Microscopy in the Diagnosis of Glomerular Diseases

To evaluate the contribution of electron microscopy to the final diagnosis of glomerulopathies, the authors established a prospective study during the first semester of 2006. A total of 52 kidney biopsies were performed with 3 samples for light microscopy, immunofluorescence, and electron microscopy. Among these renal biopsies, only 20 were examined with electron microscopy because the diagnosis made on the basis of conventional methods had remained unclear or doubtful. In 18 cases, electron microscopy was undertaken for the investigation of primary kidney disease. The 2 remaining cases were transplant biopsies. In this series of 20 patients, there were 3 children with an average age of 9 years and 17 adults with an average age of 35.5 years. Fifteen patients (75%) were nephrotic. The study revealed that electron microscopy was essential for diagnosis in 8 cases (40%) and was helpful in 12 cases (60%). In conclusion, the results showed that the ultrastructural study provides essential or helpful information in many cases of glomerular diseases, and therefore electron microscopy should be considered an important tool of diagnostic renal pathology. As was recommended, it is important to reserve renal tissue for ultrastructural study unless electron microscopy can be routinely used in all biopsies. Thus, this technique could be performed wherever a renal biopsy has to be ultrastructurally evaluated.     

Lack of electron microscopy hinders correct renal biopsy diagnosis: A study from India

Electron microscopy (EM) is performed routinely on all native kidney biopsies in the western world. However, in India, it is not regularly performed due to non-availability and financial constraints. The aim of this prospective study was to evaluate the usefulness of routinely performing EM on native kidney biopsies. In order to eliminate selection bias, all consecutive native kidney biopsies were included in this study, provided they had adequate tissue for light, immunofluorescence (IF), and EM. The biopsies were reported on the basis of light and IF microscopy. EM was performed on each case by another pathologist who also independently reviewed the light microscopic slides and IF images. The findings were then reviewed to assess how the ultrastructural features contributed to the primary diagnosis and assigned to one of the following categories: 1. Crucial for diagnosis, 2. Important contribution, or 3. Not required. Of the 115 cases evaluated, EM was crucial in 12% of the cases. In 20% of the cases, it provided important confirmatory information and in the remaining 68% cases, EM was not considered required. This study supports the use of EM as a routine diagnostic tool in the evaluation of native kidney biopsies. There is an urgent need for availability and accessibility of EM in our country.     

Value of electron microscopy in diagnosis of renal disease.

AIMS--To assess the role and value of electron microscopy in the diagnosis of renal disease. METHODS--Retrospective evaluation of 88 renal biopsy specimens received for primary diagnosis by assessment of the contribution of electron microscopy to the final diagnosis in the knowledge of the light microscopy and immunofluorescence findings. RESULTS--Electron microscopy had an important diagnostic role in 75% of cases and was essential or necessary for diagnosis in 25%. In 25% of cases electron microscopy was considered unhelpful in diagnosis. CONCLUSION--Electron microscopy has an integral role in the diagnosis of renal disease, and tissue should be taken for electron microscopy in all cases if possible. In some selected cases once the light microscopy and immunofluorescence findings are known it may be possible to forego electron microscopic examination. Electron microscopy is particularly useful in the differential diagnosis of minimal change disease and the nephrotic syndrome.     

Morphologic manifestations of combined light-chain deposition disease and light-chain cast nephropathy

There are few data on morphology of light-chain deposition disease (LCDD) of kidney with coexistent light-chain cast nephropathy (LCCN). Here, the authors report the morphology in 23 cases of LCDD and LCCN. They retrospectively evaluated 23 renal biopsies with light (LM), immunofluorescence (IF), and electron microscopy (EM). Twenty-one patients had myeloma, 1 had a monoclonal gammopathy, and in 1 no illness was found. Nodular glomerulosclerosis, the LM lesion suggestive of LCDD, was noted in only 3 of 23 cases. Glomeruli were unremarkable in 16 (69%) cases. The diagnostic casts of LCCN were seen in all biopsies. Linear light chain (LC) immunoreactivity was observed in 23 (100%) cases (18 kappa, 5 lambda); GBM + TBM in 13, TBM only in 7, GBM only in 1, TBM and interstitium in 1, GBM, TBM and mesangium in 1. Casts were positive with same LC in all cases (100%). Fifteen cases (65%) showed granular electron-dense deposits; GBM only in 5, TBM only in 5, GBM and TBM in 4, mesangium in 1. In 8 patients without EM deposits, the diagnosis of LCDD was rendered by IF. Fifteen (65%) had deposits detectable by IF and EM, 8 (37%) had deposits with IF only. LCCN dominated the LM findings in all patients. There were minimal or no glomerular changes by LM. This study shows the lack of characteristic LM findings of LCDD in combined cases of LCDD and LCCN and emphasizes the difficulty for-definitive diagnosis-without IF and EM.     

Morphologic Manifestations of Combined Light-chain Deposition Disease and Light-chain Cast Nephropathy

There are few data on morphology of light-chain deposition disease (LCDD) of kidney with coexistent light-chain cast nephropathy (LCCN). Here, the authors report the morphology in 23 cases of LCDD and LCCN. They retrospectively evaluated 23 renal biopsies with light (LM), immunofluorescence (IF), and electron microscopy (EM). Twenty-one patients had myeloma, 1 had a monoclonal gammopathy, and in 1 no illness was found. Nodular glomerulosclerosis, the LM lesion suggestive of LCDD, was noted in only 3 of 23 cases. Glomeruli were unremarkable in 16 (69%) cases. The diagnostic casts of LCCN were seen in all biopsies. Linear light chain (LC) immunoreactivity was observed in 23 (100%) cases (18 kappa, 5 lambda); GBM + TBM in 13, TBM only in 7, GBM only in 1, TBM and interstitium in 1, GBM, TBM and mesangium in 1. Casts were positive with same LC in all cases (100%). Fifteen cases (65%) showed granular electron-dense deposits; GBM only in 5, TBM only in 5, GBM and TBM in 4, mesangium in 1. In 8 patients without EM deposits, the diagnosis of LCDD was rendered by IF. Fifteen (65%) had deposits detectable by IF and EM, 8 (37%) had deposits with IF only. LCCN dominated the LM findings in all patients. There were minimal or no glomerular changes by LM. This study shows the lack of characteristic LM findings of LCDD in combined cases of LCDD and LCCN and emphasizes the difficulty for-definitive diagnosis-without IF and EM.     

Renal pathology of Waldenström's macroglobulinaemia with monoclonal antiglomerular antibodies and nephrotic syndrome.

Severe nephrotic syndrome developed suddenly in a 67-year-old man. IgM M-component and bone marrow findings indicated a diagnosis of Waldenström's macroglobulinaemia. High-titre IgM glomerular autoantibodies were found to reside mainly in the M-component. Immunofluorescent (IF) studies on serial kidney biopsies showed extensive IgM deposits that disappeared after treatment. Light microscopy of kidney biopsy appeared only slightly altered, but combined with electron microscopy could demonstrate changes that correlated well with IF findings. The latest biopsy showed interstitial infiltration in the kidney of atypical lympho-histiocytic cells. Morphological and immunological examination indicated that pathogenetic events started with minimal-change glomerulonephritis, causing release of glomerular antigen, that finally triggered a monoclonal IgM response and lymphoproliferative reaction. Intermittent treatment with chlorambucil and corticoids completely abolished the nephrotic syndrome and at the same time the changes in renal morphology largely disappeared.     

Ultrastructure of tubular casts

Tubular casts are found in a variety of conditions. Ultrastructural evaluation of casts has not been critically and systematically performed to define its usefulness. A total of 157 renal biopsies routinely processed for light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM) were subjected to blind ultrastructural evaluation. The majority of the casts were in the distal nephron, and most of them (41.4%) were hyaline (HC). One-third (35%) of the cases showed admixed HC and granular casts (GC), and 25 cases (16%) had exclusively GC. In 7% of the cases, the morphology of the casts was distinctive enough to indicate specific composition. Four cases with red blood cell casts (5.6%) were associated with necrotizing glomerulopathy and IgA nephropathy. Four cases of myoglobulin casts were identified. Two cases with crystalized light-chain casts (1.3%) were associated with an underlying plasma cell dyscrasia. One case of acute pyelonephritis demonstrated polymorphonuclear cells casts (0.64%). A case of aminoglycoside toxicity revealed casts with myeloid bodies. Ultrastructural evaluation of casts may provide useful information that may be critical to establish or suggest a specific diagnosis.     

肾脏早期淀粉样变临床病理特点

目的 探讨光学显微镜尚未表现明显特点的早期肾淀粉样变(amyloidosis,AL)的临床病理特点及诊断方法。方法 回顾性分析该院1994-2001年间诊断的肾AL病例,重点对其中15例光镜未能及时诊断而通过透射电镜诊断的早期AL病例,进行临床病理特点的分析,并对其肾活检组织进行了轻链蛋白(κ、λ)的免疫电镜定位检测。结果 15例均为早期肾AL,发病年龄以中老年为主,突出表现为肾病综合征,偶见镜下血尿及高血压,肾功能正常。多数以肾脏病为初诊症状。肾活检组织光镜观察病变表现轻微,可有系膜轻度增生或基底膜空泡变性及轻度增厚;免疫荧光表现不一,部分病例全部阴性,部分表现免疫球蛋白及补体沿系膜区或毛细血管壁不同程度的沉积,均有单一品种的轻链蛋白沉积;光镜初步诊断为肾小球微小病变4例,轻度系膜增生性肾小球肾炎5例,I期膜性肾病5例和1例管型肾病;电镜观察可见系膜区、基底膜及小动脉壁上的淀粉样纤维分布;补作刚果红染色时,呈阳性反应;免疫电镜可观察到轻链蛋白被标记于淀粉样纤维部位,证实15例均为轻链型AL。结论 电镜检查是发现及早期诊断肾淀粉样变的重要手段,单一品种的轻链蛋白沉积有一定的诊断意义,结合免疫电镜检查可进一步确诊和分型。     

Morphologic Heterogeneity of Renal Light-Chain Deposition Disease

Light-chain deposition disease (LCDD) of the kidney is defined as deposition of monotypic light chains (LC) within glomerular (GBM) and tubular (TBM) basement membranes. The morphologic features of pure renal LCDD have been presented only in case reports or small series. The aim of this study was to perform a comprehensive evaluation of the light (LM), immunofluorescence (IF), and electron microscopic (EM) features of pure renal LCDD in a large series of biopsies. Out of 46 cases assembled, 42 had multiple myeloma, 2 had monoclonal gammopathy of unknown significance, and in 2 patients no lymphoproliferative disease was identified. The most common LM lesion of LCDD, nodular glomerulosclerosis, was present in only 14 (30%) cases. GBM and/or TBM thickening was found in 3 (6%), mild to moderate mesangial matrix increase in 12 (23%), and unremarkable glomeruli and tubules were seen in 15 (32%) cases. Forty-two had IF and 40 (92%) showed characteristic linear LC immunoreactivity (24 kappa, 16 lambda) along GBM and/or TBM. Among 39 cases in which IF and EM was available, 25 (64%) were positive by both. Two (6%) were negative by IF, but had deposits by EM. In 12 (30%) with immunoreactivity to LC (4 kappa, 8 lambda), no deposits were identified ultrastructurally. This study shows heterogeneous LM lesions in pure LCDD cases. LM alone may be suspicious but not diagnostic of LCDD. Immunofluorescence is more sensitive than EM for detection of LC for the definitive diagnosis of LCDD. This study supports the importance of utilizing kappa and lambda stains in the routine IF panel for diagnosis of LCDD.     

Morphologic heterogeneity of renal light-chain deposition disease

Light-chain deposition disease (LCDD) of the kidney is defined as deposition of monotypic light chains (LC) within glomerular (GBM) and tubular (TBM) basement membranes. The morphologic features of pure renal LCDD have been presented only in case reports or small series. The aim of this study was to perform a comprehensive evaluation of the light (LM), immunofluorescence (IF), and electron microscopic (EM) features of pure renal LCDD in a large series of biopsies. Out of 46 cases assembled, 42 had multiple myeloma, 2 had monoclonal gammopathy of unknown significance, and in 2 patients no lymphoproliferative disease was identified. The most common LM lesion of LCDD, nodular glomerulosclerosis, was present in only 14 (30%) cases. GBM and/or TBM thickening was found in 3 (6%), mild to moderate mesangial matrix increase in 12 (23%), and unremarkable glomeruli and tubules were seen in 15 (32%) cases. Forty-two had IF and 40 (92%) showed characteristic linear LC immunoreactivity (24 kappa, 16 lambda) along GBM and/or TBM. Among 39 cases in which IF and EM was available, 25 (64%) were positive by both. Two (6%) were negative by IF, but had deposits by EM. In 12 (30%) with immunoreactivity to LC (4 kappa, 8 lambda), no deposits were identified ultrastructurally. This study shows heterogeneous LM lesions in pure LCDD cases. LM alone may be suspicious but not diagnostic of LCDD. Immunofluorescence is more sensitive than EM for detection of LC for the definitive diagnosis of LCDD. This study supports the importance of utilizing kappa and lambda stains in the routine IF panel for diagnosis of LCDD.     

Electron microscopic study of infantile renal biopsy specimens

Out of 54 open renal biopsies performed on children, 17 were selected and studied not only by light microscopy but also by electron microscopy. Statistical-mathematical analysis of basement membrane thickness-measurements was carried out. It is concluded that electron microscopic investigation of the renal biopsy material is required in selected cases involving diagnostic or therapeutic problems. In nephrotic syndrome it may help above all to separate minimal changes from early forms or glomerular lesion of the focal sclerosing type. Electron microscopy can also be useful in any of the mono- and oligosymptomatic renal diseases. In those cases only electron microscopy makes it possible to provide exact morphological diagnosis which is necessary to the proper therapy.     

Value of Electron Microscopy in Kidney Biopsy Diagnosis

Kidney biopsy reports given during 2003 were collected from the authors' pathology database. A total of 111 biopsies were performed. Five tumor samples were not studied with electron microscopy (EM). Of the remaining 106 biopsies, 85 were studied with EM. EM was not performed in 10/24 transplant biopsies, or in 11/82 cases of suspected primary kidney disease. The role of EM was evaluated by grouping the samples in 3 categories: (1) EM was essential for diagnosis, (2) EM contributed to the interpretation and cleared uncertainties, and (3) EM had no influence on the diagnostic process. In transplant biopsies EM influenced the final diagnosis in 86% of cases (category 2). In biopsies performed for primary kidney disease EM was essential for diagnosis in 18.3% clearly contributed in 53.5%, and had no influence on the final diagnosis in 28.2% of cases. The study suggests that the importance of EM has not decreased during the last few years. Because only about 25% of the EM reports did not have any influence on the diagnostic process, it is recommended that kidney biopsy protocols should include EM in all biopsy cases, or at least tissue should be reserved for EM studies of all cases. Because of the influence of EM on the diagnostic process the need for EM in pathology training should be emphasized.     

Actual practices in nephropathology: a survey and comparison with best practices

Nephropathology is a specialized field requiring routine tissue evaluation by immunofluorescence (IF), electron microscopy (EM), and light microscopy, and has published standards of best practice. Actual practices are less well documented. We therefore evaluated actual practices in nephropathology and their divergence from best practices. One hundred and twenty Renal Pathology Society members were given questionnaires regarding tissue handling, processing, and staining. Appropriate statistics for each question were calculated from results compiled into Microsoft Excel. Responses from 75 members showed that most received 16 or 18 gauge core biopsies, examined 9 slides for native kidneys, 8 slides for transplant kidneys, and for both used hematoxylin and eosin, periodic acid-Schiff, trichrome, and silver stains. For native kidney biopsies, most collected for IF and EM if tissue was adequate, while clinical input could influence the rest. Almost all performed IF on adequate samples, with a minimum of 8 antibodies, including both light chains, those from Europe sometimes without proof of adequacy. Half performed EM unconditionally, the remainder based on specimen adequacy or clinical input. For transplant kidney biopsies, most collected tissue for IF and EM only with specific clinical indications, performed C4d IF on frozen tissue if available, but few used the native kidney IF panel. Very few performed EM unconditionally, but most would if given specific indications. We conclude that actual nephropathology practices within the Renal Pathology Society are geographically uniform and similar to published best practices, with divergence in performing IF and EM on the basis of specimen adequacy and clinical input, particularly in transplant biopsies.     

Value of electron microscopy in kidney biopsy diagnosis

Kidney biopsy reports given during 2003 were collected from the authors' pathology database. A total of 111 biopsies were performed. Five tumor samples were not studied with electron microscopy (EM). Of the remaining 106 biopsies, 85 were studied with EM. EM was not performed in 10/24 transplant biopsies, or in 11/82 cases of suspected primary kidney disease. The role of EM was evaluated by grouping the samples in 3 categories: (1) EM was essential for diagnosis, (2) EM contributed to the interpretation and cleared uncertainties, and (3) EM had no influence on the diagnostic process. In transplant biopsies EM influenced the final diagnosis in 86% of cases (category 2). In biopsies performed for primary kidney disease EM was essential for diagnosis in 18.3% clearly contributed in 53.5%, and had no influence on the final diagnosis in 28.2% of cases. The study suggests that the importance of EM has not decreased during the last few years. Because only about 25% of the EM reports did not have any influence on the diagnostic process, it is recommended that kidney biopsy protocols should include EM in all biopsy cases, or at least tissue should be reserved for EM studies of all cases. Because of the influence of EM on the diagnostic process the need for EM in pathology training should be emphasized.     

The pathological spectrum associated with the ultrastructural finding of thin glomerular basement membrane: A tertiary medical city experience and review of the literature

Background: Thin glomerular basement membrane (GBM) has been noted in several glomerular diseases including IgA nephropathy, focal segmental glomerulosclerosis (FSGS), Fabry’s disease, and Alport’s syndrome. We conducted this study to investigate the pathological ultrastructural spectrum of thin GBMs, to identify associated diseases, and to measure the GBM thickness in thin GBMs in our adult population. Materials and methods: All renal biopsies with thin GBM, diagnosed between 2010 and 2016, were retrieved and reviewed. Results: Of 24 cases, 50.0% were diagnosed with FSGS, 12.5% with IgA nephropathy, 8.3% with tubulointerstitial nephritis, 4.2% with acute thrombotic microangiopathy, 4.2% with focal global sclerosis, 4.2% with lupus nephritis, and 16.7% with only thin GBM disease. Mean GBM thickness was 213.4 ± 24.7 nm. Mean interstitial fibrosis/tubular atrophy percentage (IF/TA) was 27.9 ± 22.2%. There was no significant correlation between GBM thickness and patients’ age or IF/TA percentage. Conclusion: The association of thin GBM with FSGS and IgA nephropathy is high. Morphometric analysis of the GBM thickness should be made routine, noting that ethnic variations in the GBM thickness are reported. Cases of thin GBM should be reported to facilitate proper diagnosis and institute the most appropriate treatment.     

Role of Electron Microscopy in the Diagnosis of Nonneoplastic Renal Disease in Children

To assess the role of electron microscopy in the evaluation of pediatric renal biopsies, all native kidney biopsies performed in children for nonneoplastic renal disease over a 2-year period were reviewed. Of 80 biopsies, the role of electron microscopy was classified as “essential” in 50 (63%), “supportive or confirmatory” in 18 (23%), and “noncontributory” in 9 (11%), with no glomeruli available for study in 3 (4%). The role of electron microscopy with respect to indication for biopsy and final diagnosis is discussed. This study confirms the continued importance of electron microscopy in the evaluation of pediatric renal biopsies.     

Role of electron microscopy in the diagnosis of nonneoplastic renal disease in children

To assess the role of electron microscopy in the evaluation of pediatric renal biopsies, all native kidney biopsies performed in children for nonneoplastic renal disease over a 2-year period were reviewed. Of 80 biopsies, the role of electron microscopy was classified as "essential" in 50 (63%), "supportive or confirmatory" in 18 (23%), and "noncontributory" in 9 (11%), with no glomeruli available for study in 3 (4%). The role of electron microscopy with respect to indication for biopsy and final diagnosis is discussed. This study confirms the continued importance of electron microscopy in the evaluation of pediatric renal biopsies.