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Uzun O, Heybeli C, Kutlu FSA, Celebioglu Pekiner M, Yıldırım F, Cavdar C, Sarioglu S. Relationship between complement and macrophage markers with kidney survival in patients with diabetic nephropathy. Acta Diabetol 2025:10.1007/s00592-025-02521-3. [PMID: 40338344 DOI: 10.1007/s00592-025-02521-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 04/21/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease (ESKD) worldwide. Macrophages and the complement system have interrelated roles in DN. We aimed to determine associations between macrophage and complement markers with the progression of DN. METHODS This retrospective cohort study included patients diagnosed with sole DN by kidney biopsy. Using immunohistochemistry, CD68+ and CD163+ cells and complement markers were counted in glomerular and tubulointerstitial areas. The primary outcome was evolution to ESKD and/or doubling serum creatinine (SCr). RESULTS Forty-six patients were included. The median SCr at baseline was 2.7 (1.41-3.1) mg/dL. During the median follow-up of 32 months (range 6-54), 50% of patients reached the primary outcome. Most of the clinical and histological findings were comparable between progressors and non-progressors, while progressors had a higher median number of glomerular CD68+ cells and a higher percentage of glomerulosclerosis. After adjustments for age, sex, and SCr, the median glomerular CD68+ cell number was the sole independent predictor of progression. Glomerular C4d was associated with nephrotic-range proteinuria but not with the progression of kidney failure. CONCLUSIONS Glomerular CD68+ cell count may serve as a promising predictor of kidney disease progression among patients with DN. Glomerular C4d was associated with nephrotic-range proteinuria but not with the progression of kidney failure.
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Affiliation(s)
- Ozcan Uzun
- Yalova Research and Training Hospital, Yalova, Turkey
| | - Cihan Heybeli
- Division of Nephrology, Dokuz Eylül University School of Medicine, Izmir, Turkey.
| | | | | | | | - Caner Cavdar
- Division of Nephrology, Dokuz Eylül University School of Medicine, Izmir, Turkey
| | - Sulen Sarioglu
- Department of Pathology, Dokuz Eylül University School of Medicine, Izmir, Turkey
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2
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Yamashita M, Piaseczna N, Takahashi A, Kiyozawa D, Tatsumoto N, Kaneko S, Zurek N, Gertych A. AI-driven glomerular morphology quantification: a novel pipeline for assessing basement membrane thickness and podocyte foot process effacement in kidney diseases. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2025; 268:108842. [PMID: 40354728 DOI: 10.1016/j.cmpb.2025.108842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 04/25/2025] [Accepted: 05/06/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND AND OBJECTIVE Measuring the thickness of the glomerular basement membrane (GBM) and assessing the percentage of podocyte foot process effacement (%PFPE) are important for diagnosing non-neoplastic kidney diseases. However, when performed manually by nephropathologists using electron microscopy (EM) images, these assessments are hindered by the lack of universally standardized guidelines, leading to technical challenges. We have developed a novel deep learning (DL)-based pipeline which has the potential to reduce human error and enhance the consistency and efficiency of GBMs and %PFPE quantifications. METHODS This study utilized 196 EM images from kidney biopsies (representing 21 different kidney diseases from 83 subjects) which were manually annotated by consensus of 3 nephrologists and 2 nephropathologist providing ground truth (GT) masks of GBMs, podocytes, red blood cells and other glomerular ultrastructures. Of these, 165 images were used to develop two DL models (DeepLabV3+ and U-Net architectures) for EM image segmentation. Subsequently, the models were evaluated on the remaining 31 images and compared for segmentation accuracy, and the predicted GBM and podocyte masks were analyzed by algorithms in the pipeline which automatically measured the corrected harmonic mean of GBM thickness (cmGBM) and estimated the %PFPE. The automated measurements were statistically compared to the corresponding cmGBM measured and %PFPE estimated using the consensus GBM and podocyte GT masks. The goal was to identify differences between measurements provided by these three methods. Statistical evaluations were carried out using the intraclass correlation coefficient (ICC), and the Bland-Altman plots estimating the bias and limits of agreement (LoAs) between the GT and DL mask-based measurements. RESULTS In the 31 test set images, the DeepLabV3+ model achieved a global accuracy (gACC) of 92.8 % and a weighted intersection over union (wIoU) of 0.869, outperforming the U-Net model, which recorded a gACC of 88.9 % and a wIoU of 0.800. For GBM thickness measurements, the cmGBM derived from DeepLabV3+ masks exhibited excellent agreement with GT-masks based measurements (ICC = 0.991, p < 0.001), whereas the U-Net model showed good agreement (ICC = 0.881, p < 0.001). The %PFPE estimates obtained using the DL-generated podocyte masks were highly consistent with those based on GT, with ICC values of 0.926 and 0.928 for DeepLabV3+ and U-Net, respectively. The Bland-Altman plots revealed a positive bias in the cmGBM and %PFPE obtained from the masks generated by the DeepLabV3+ model, and negative bias in the cmGBM and %PFPE obtained from the masks generated by the U-Net model. However, the DeepLabV3+ masks provided narrower LoA ranges than the U-Net masks for measuring cmGBM. CONCLUSIONS This study highlights the potential of AI to address the limitations of manual assessments of glomerular ultrastructures in EM images by providing comprehensive, objective and accurate measurements of GBM thickness and %PFPE estimates. Our pipeline with DeepLabV3+ demonstrated robust EM image segmentation efficiency and excellent reliability of measurements when compared to expert ground truth. Further refinement of this AI-driven method for advancing the diagnostic capabilities and standardization of AI in nephropathology is warranted.
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Affiliation(s)
- Michifumi Yamashita
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Natalia Piaseczna
- Faculty of Biomedical Engineering, Silesian University of Technology, Zabrze, Poland; Innovation Centre for Digital Medicine, National Information Processing Institute, Warsaw, Poland
| | - Akira Takahashi
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
| | - Daisuke Kiyozawa
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Narihito Tatsumoto
- Diabetes Thyroid Endocrinology Center, Shinkoga Hospital, Fukuoka, Japan
| | - Shohei Kaneko
- Department of Nephrology, Saitama Citizens Medical Center, Saitama, Japan
| | - Natalia Zurek
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Arkadiusz Gertych
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States; Faculty of Biomedical Engineering, Silesian University of Technology, Zabrze, Poland; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
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3
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Pan S, Tang X, Chen B, Lai X, Jin W. GlomSAM: Hybrid customized SAM for multi-glomerular detection and segmentation in immunofluorescence images. PLoS One 2025; 20:e0321096. [PMID: 40228213 PMCID: PMC11996217 DOI: 10.1371/journal.pone.0321096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/28/2025] [Indexed: 04/16/2025] Open
Abstract
In nephrology research, multi-glomerular segmentation in immunofluorescence images plays a crucial role in the early detection and diagnosis of chronic kidney disease. However, obtaining accurate segmentations often requires labor-intensive annotations and existing methods are hampered by low recall rates and limited accuracy. Recently, a general Segment Anything Model (SAM) has demonstrated promising performance in several segmentation tasks. In this paper, a SAM-based multi-glomerular segmentation model (GlomSAM) is introduced to employ SAM in the immunofluorescence pathology domain. The fusion encoder strategy utilizing the advantages of both convolution networks and transformer structures with prompts is conducted to facilitate SAM's transfer learning in applications of pathological analysis. Moreover, a rough mask generator is employed to generate preliminary glomerular segmentation masks, enabling automated input prompting and improving the final segmentation results. Extensive comparative experiments and ablation studies show its state-of-the-art performance surpassing other relevant research. We hope this report will provide insights to advance the field of glomerular segmentation and promote more interesting work in the future.
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Affiliation(s)
- Shengyu Pan
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China
| | - Xuanli Tang
- Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Bingxian Chen
- Ningbo KonFoong Bioinformation Tech Co. Ltd, Ningbo, Zhejiang, China
| | - Xiaobo Lai
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China
| | - Wei Jin
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China
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4
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Rieder F, Nagy LE, Maher TM, Distler JHW, Kramann R, Hinz B, Prunotto M. Fibrosis: cross-organ biology and pathways to development of innovative drugs. Nat Rev Drug Discov 2025:10.1038/s41573-025-01158-9. [PMID: 40102636 DOI: 10.1038/s41573-025-01158-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2025] [Indexed: 03/20/2025]
Abstract
Fibrosis is a pathophysiological mechanism involved in chronic and progressive diseases that results in excessive tissue scarring. Diseases associated with fibrosis include metabolic dysfunction-associated steatohepatitis (MASH), inflammatory bowel diseases (IBDs), chronic kidney disease (CKD), idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc), which are collectively responsible for substantial morbidity and mortality. Although a few drugs with direct antifibrotic activity are approved for pulmonary fibrosis and considerable progress has been made in the understanding of mechanisms of fibrosis, translation of this knowledge into effective therapies continues to be limited and challenging. With the aim of assisting developers of novel antifibrotic drugs, this Review integrates viewpoints of biologists and physician-scientists on core pathways involved in fibrosis across organs, as well as on specific characteristics and approaches to assess therapeutic interventions for fibrotic diseases of the lung, gut, kidney, skin and liver. This discussion is used as a basis to propose strategies to improve the translation of potential antifibrotic therapies.
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Affiliation(s)
- Florian Rieder
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
- Program for Global Translational Inflammatory Bowel Diseases (GRID), Chicago, IL, USA.
| | - Laura E Nagy
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
- Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA
| | - Toby M Maher
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- National Heart and Lung Institute, Imperial College, London, UK
| | - Jörg H W Distler
- Department of Rheumatology, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
- Hiller Research Center, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
| | - Rafael Kramann
- Department of Nephrology and Clinical Immunology, RWTH Aachen; Medical Faculty, Aachen, Germany
- Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, Netherlands
| | - Boris Hinz
- Keenan Research Institute for Biomedical Science of the St Michael's Hospital, Toronto, Ontario, Canada
- Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | - Marco Prunotto
- Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.
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5
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Cui HY, Li C, Wen YB, Ye W, Ye WL, Li H, Chen LM. Clinicopathological characteristics of patients with low titer anti-phospholipase A2 receptor antibodies verified by indirect immunofluorescence assay. Clin Chim Acta 2025; 567:120070. [PMID: 39631493 DOI: 10.1016/j.cca.2024.120070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/27/2024] [Accepted: 11/30/2024] [Indexed: 12/07/2024]
Abstract
OBJECTIVE Laboratory extensively applied enzyme-linked immunosorbent assay (ELISA) to measure anti-phospholipase A2 receptor antibodies (PLA2R-abs) since its diagnostic significance on PLA2R related primary membranous nephropathy (PLA2R-related pMN) was discovered. However, PLA2R-abs determined by ELISA (PLA2R-ELISA) could infrequently yield inconclusive results, specifically a grey-zone defined as PLA2R-abs ranging from 2 to 20 RU/mL. Recently, researchers suggested that double-check grey-zone PLA2R-abs by indirect immunofluorescence (IIF) could improve diagnostic accuracy. We evaluated the diagnostic performance of PLA2R-IIF in assessing PLA2R-related pMN and summarized clinicopathological characteristics of grey-zone population to provide more evidence for clinical practice. METHODS Data on demographics, serology and pathology of patients with PLA2R-ELISA grey-zone results and a native kidney biopsy at Peking Union Medical College Hospital from September 2020 to April 2023 were reviewed. Grey-zone samples were analyzed using PLA2R-IIF. Negative results were defined as no fluorescence and positive results were graded according to fluorescence intensity. RESULTS This study included a total of 52 grey-zone patients divided into pMN group (n = 36, 69 %) and non-pMN group (n = 16, 31 %) according to renal pathology reports. The pMN patients had higher PLA2R-abs and lower serum creatinine compared to the non-pMN patients (P = 0.003, P < 0.001). No statistically significant differences were observed in 24-hour urine protein and albumin between the two groups. Multiple pathological types were identified in the non-pMN group. The sensitivity and specificity of PLA2R-IIF in PLA2R-ELISA grey-zone population were 72 % and 88 %, respectively, with a total consistent rate of 77 % and a positive predictive value of 93 %. CONCLUSION Both pMN and non-pMN patients presented grey-zone PLA2R-ELISA results. It was necessary to perform PLA2R-IIF to assist in the diagnosis of patients with PLA2R-ELISA grey-zone results.
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Affiliation(s)
- Hao-Yuan Cui
- Nephrology Division, Peking Union Medical College Hospital, No 1, Shuaifuyuan, Wangfujing St, Beijing 100730, PR China
| | - Chao Li
- Nephrology Division, Peking Union Medical College Hospital, No 1, Shuaifuyuan, Wangfujing St, Beijing 100730, PR China
| | - Yu-Bing Wen
- Nephrology Division, Peking Union Medical College Hospital, No 1, Shuaifuyuan, Wangfujing St, Beijing 100730, PR China
| | - Wei Ye
- Nephrology Division, Peking Union Medical College Hospital, No 1, Shuaifuyuan, Wangfujing St, Beijing 100730, PR China
| | - Wen-Ling Ye
- Nephrology Division, Peking Union Medical College Hospital, No 1, Shuaifuyuan, Wangfujing St, Beijing 100730, PR China
| | - Hang Li
- Nephrology Division, Peking Union Medical College Hospital, No 1, Shuaifuyuan, Wangfujing St, Beijing 100730, PR China.
| | - Li-Meng Chen
- Nephrology Division, Peking Union Medical College Hospital, No 1, Shuaifuyuan, Wangfujing St, Beijing 100730, PR China
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6
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Yunker L, Harwig MC, Kriegel AJ. A novel automated method for comprehensive renal cast quantification from rat kidney sections using QuPath. Am J Physiol Renal Physiol 2025; 328:F230-F238. [PMID: 39716935 DOI: 10.1152/ajprenal.00252.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 11/21/2024] [Accepted: 12/08/2024] [Indexed: 12/25/2024] Open
Abstract
The presence of tubular casts within the kidney serves as an important feature when assessing the degree of renal injury. Quantification of renal tubular casts has been historically difficult due to varying cast morphologies, protein composition, and stain uptake properties, even within the same kidney. Color thresholding remains one of the most common methods of quantification in the laboratory when assessing the percentage of renal casting; however, this method is unable to account for tubule casts stained a variety of colors. We have developed a novel method of automated cast quantification using the machine learning pixel classification tool within QuPath, an open-source software designed for digital pathology. We demonstrated the usability of this method in male and female Dahl salt-sensitive rats fed either low or high salt for 2 wk and male Sprague-Dawley rats treated with podotoxin puromycin aminonucleoside (PAN). Briefly, the pixel classifier was trained to identify kidney tissue, various cast color types, and slide backgrounds. Following the development of the pixel classifier, we applied it to the sample population and compared the results with those of other methods of cast quantification, including color thresholding and manual quantification. We found that the automated pixel classifier designed in QuPath was able to comprehensively quantify metachromatic tubular casts compared with color thresholding. This novel method of cast quantification provides researchers with the ability to reliably automate cast quantification that is both comprehensive and efficient.NEW & NOTEWORTHY We developed a method of automated renal tubule cast quantification using a machine learning-based pixel classifier within QuPath, an open-source image analysis software. The advantages of this approach are demonstrated by rigorous comparison of quantification methods on a set of Masson's trichrome-stained kidney sections from high- and low-salt fed salt-sensitive Dahl rats. Researchers are provided with step-by-step instructions for creating and training a pixel classifier in QuPath for application to image analysis.
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Affiliation(s)
- Lauren Yunker
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Megan Cleland Harwig
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Alison J Kriegel
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, United States
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7
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Laue M. Diagnostic electron microscopy in human infectious diseases - Methods and applications. J Microsc 2024. [PMID: 39560601 DOI: 10.1111/jmi.13370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/30/2024] [Indexed: 11/20/2024]
Abstract
Diagnostic electron microscopy (EM) is indispensable in all cases of infectious diseases which deserve or profit from the detection of the entire pathogen (i.e. the infectious unit). The focus of its application has shifted during the last decades from routine diagnostics to diagnostics of special cases, emergencies and the investigation of disease pathogenesis. While the focus of application has changed, the methods remain more or less the same. However, since the number of cases for diagnostic EM has declined as the number of laboratories that are able to perform such investigations, the preservation of the present knowledge is important. The aim of this article is to provide a review of the methods and strategies which are useful for diagnostic EM related to infectious diseases in our days. It also addresses weaknesses as well as useful variants or extensions of established methods. The main techniques, negative staining and thin section EM, are described in detail with links to suitable protocols and more recent improvements, such as thin section EM of small volume suspensions. Sample collection, transport and conservation/inactivation are discussed. Strategies of sample examination and requirements for a proper recognition of structures are outlined. Finally, some examples for the actual application of diagnostic EM related to infectious diseases are presented. The outlook section will discuss recent trends in microscopy, such as automated object recognition by machine learning, regarding their potential in supporting diagnostic EM.
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Affiliation(s)
- Michael Laue
- Centre for Biological Threats and Special Pathogens (ZBS 4), Advanced Light and Electron Microscopy, Robert Koch Institute, Berlin, Germany
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8
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Ahangaran M, Sun E, Le K, Sun J, Wang WM, Tan TH, Yin L, Burdine LJ, Dvanajscak Z, Cassol CA, Sharma S, Kolachalama VB. Pilot Study of a Web-Based Tool for Real-Time Adequacy Assessment of Kidney Biopsies. Kidney Int Rep 2024; 9:2809-2813. [PMID: 39291211 PMCID: PMC11403039 DOI: 10.1016/j.ekir.2024.06.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/22/2024] [Accepted: 06/10/2024] [Indexed: 09/19/2024] Open
Affiliation(s)
- Meysam Ahangaran
- Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Emily Sun
- Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Khang Le
- Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Jiawei Sun
- Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - William M. Wang
- Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Tian Herng Tan
- Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Lingkai Yin
- Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Lyle J. Burdine
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | | | | | | | - Vijaya B. Kolachalama
- Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Computer Science and Faculty of Computing & Data Sciences, Boston University, Boston, Massachusetts, USA
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Bindi G, Pagani L, Ceku J, de Oliveira GS, Porto NS, Monza N, Denti V, Mescia F, Chinello C, Fraggetta F, Magni F, Pagni F, Alberici F, L'Imperio V, Smith A. Feasibility of MALDI-MSI-Based Proteomics Using Bouin-Fixed Pathology Samples: Untapping the Goldmine of Nephropathology Archives. J Proteome Res 2024; 23:2542-2551. [PMID: 38869849 DOI: 10.1021/acs.jproteome.4c00198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2024]
Abstract
The application of innovative spatial proteomics techniques, such as those based upon matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technology, has the potential to impact research in the field of nephropathology. Notwithstanding, the possibility to apply this technology in more routine diagnostic contexts remains limited by the alternative fixatives employed by this ultraspecialized diagnostic field, where most nephropathology laboratories worldwide use bouin-fixed paraffin-embedded (BFPE) samples. Here, the feasibility of performing MALDI-MSI on BFPE renal tissue is explored, evaluating variability within the trypsin-digested proteome as a result of different preanalytical conditions and comparing them with the more standardized formalin-fixed paraffin-embedded (FFPE) counterparts. A large proportion of the features (270, 68.9%) was detected in both BFPE and FFPE renal samples, demonstrating only limited variability in signal intensity (10.22-10.06%). Samples processed with either fixative were able to discriminate the principal parenchyma regions along with diverse renal substructures, such as glomeruli, tubules, and vessels. This was observed when performing an additional "stress test", showing comparable results in both BFPE and FFPE samples when the distribution of several amyloid fingerprint proteins was mapped. These results suggest the utility of BFPE tissue specimens in MSI-based nephropathology research, further widening their application in this field.
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Affiliation(s)
- Greta Bindi
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
| | - Lisa Pagani
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
| | - Joranda Ceku
- Department of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo dei Tintori, University of Milano-Bicocca, Monza 20900, MB, Italy
| | - Glenda Santos de Oliveira
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
| | - Natalia Shelly Porto
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
| | - Nicole Monza
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
| | - Vanna Denti
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
| | - Federica Mescia
- Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia 25123, BS, Italy
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, BS, Italy
| | - Clizia Chinello
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
| | - Filippo Fraggetta
- Pathology Unit, Gravina Hospital Caltagirone, ASP Catania, Caltagirone 95041, CT, Italy
| | - Fulvio Magni
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
| | - Fabio Pagni
- Department of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo dei Tintori, University of Milano-Bicocca, Monza 20900, MB, Italy
| | - Federico Alberici
- Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia 25123, BS, Italy
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, BS, Italy
| | - Vincenzo L'Imperio
- Department of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo dei Tintori, University of Milano-Bicocca, Monza 20900, MB, Italy
| | - Andrew Smith
- Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, Vedano al Lambro 20854, MB, Italy
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10
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Büttner-Herold M, Amann K. [Introduction to renal pathology]. PATHOLOGIE (HEIDELBERG, GERMANY) 2024; 45:241-245. [PMID: 38512473 DOI: 10.1007/s00292-024-01310-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/29/2024] [Indexed: 03/23/2024]
Abstract
In recent decades, nephropathology has developed worldwide as a subspeciality of pathology, which requires special methodological and technical equipment to process the material and specific clinical and pathological expertise to interpret the findings. These special requirements mean that nephropathology is not available at all pathology institutes, but is carried out on a large scale in a few highly specialised centres. The history of nephropathology, or in a narrower sense the specialised histopathological examination of kidney biopsies, began in 1958 with the first use or performance of a kidney biopsy [1]. It thus replaced the practice of urinalysis, which had been common since the Middle Ages, as a diagnostic tool for kidney diseases. Specialised techniques such as immunofluorescence or immunohistology but also electron microscopy are required to assess specific renal changes, for which the examination of renal biopsies is one of the few remaining routine applications today. In Germany and German-speaking countries, the discipline developed thanks to the work of outstanding people in the field of pathology who were primarily involved in this discipline and had the necessary technical and human resources in their laboratories to ensure that these biopsies could be analysed.
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Affiliation(s)
- Maike Büttner-Herold
- Abteilung Nephropathologie, Institut für Pathologie, Universitätsklinikum Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Deutschland
| | - Kerstin Amann
- Abteilung Nephropathologie, Institut für Pathologie, Universitätsklinikum Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Deutschland.
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Modi SS, Ramamurthy S, Balasubramanian S, Kumar S, Daruwala F. Bedside Method to Check the Adequacy of Kidney Biopsy Sample with a Smartphone Camera and Macro Lenses: A Prospective Cohort Study. Indian J Nephrol 2024; 34:233-236. [PMID: 39114388 PMCID: PMC11302506 DOI: 10.4103/ijn.ijn_323_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 08/08/2023] [Indexed: 08/10/2024] Open
Abstract
Background The utilization of smartphone-assisted evaluation is emerging in the field of histopathology. This technique improves the adequacy of samples at the bedside, avoids procedure-related complications, reduces unnecessary repeat biopsies, and saves the cost of the procedure. This study aims to compare the number of glomeruli in a renal biopsy specimen obtained by an ultrasound-guided percutaneous needle biopsy, counted at the bedside using a smartphone fitted with a 16-megapixel macro lens (Bedside method) with that observed under a light microscope after the processing of the biopsy specimen (LM method). Materials and Methods In this prospective cohort study, 24 consecutive adult patients (48 kidney biopsy samples) who underwent kidney biopsies were enrolled. All specimens were extracted by an ultrasound-guided percutaneous renal biopsy from the lower pole of the left kidney. Patients' demographics and clinical data were prospectively collected. The number of glomeruli in all the biopsy specimens was counted using a smartphone fitted with a 16-megapixel macro lens at the bedside (Bedside method) and subsequently under a light microscope by a pathologist after processing the biopsy specimen (LM method). Seven or more glomeruli in the specimen were considered adequate in our study. Results The mean age of patients at biopsy was 46.9 ± 16 years with slightly male predominance (54.2%). A total of 47 specimens were obtained from 24 patients. Of the 24 patients, 22 had native kidney biopsy and 2 had renal allograft biopsy. The average number of cores obtained per patient was 1.96. The length of core specimens ranged from 1.5 to 2 cm. A good agreement was found between bedside adequacy and slide adequacy, κ =0.684, P = 0.000. The positive agreement rate and negative agreement rate were 91.4% and 23.1%, respectively. Conclusion In the modern era of technology, the smartphone is a good tool to evaluate the adequacy of biopsy specimens at the bedside.
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Affiliation(s)
- Suny S. Modi
- Department of Nephrology, Vishesh – Jupiter Hospital, Indore, Madhya Pradesh, India
| | - Satheesh Ramamurthy
- Department of Interventional Radiology, Apollo Hospitals, Chennai, Tamil Nadu, India
| | | | - Sunil Kumar
- Department of Renal Pathology, Apollo Hospitals, Chennai, Tamil Nadu, India
| | - Feral Daruwala
- Department of Medical Writer, NEPHROLIFE-The Complete Kidney Care, Surat, Gujarat, India
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12
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Zhang H, Haun RS, Collin F, Cassol C, Napier JOH, Wilson J, Hassen S, Ararat K, Boils C, Messias N, Caza TN, Cossey LN, Sharma S, Ambruzs JM, Agrawal N, Shekhtman G, Tian W, Srinivas T, Qu K, Woodward RN, Larsen CP, Stone S, Coley SM. Development and Validation of a Multiclass Model Defining Molecular Archetypes of Kidney Transplant Rejection: A Large Cohort Study of the Banff Human Organ Transplant Gene Expression Panel. J Transl Med 2024; 104:100304. [PMID: 38092179 DOI: 10.1016/j.labinv.2023.100304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 11/19/2023] [Accepted: 12/06/2023] [Indexed: 01/15/2024] Open
Abstract
Gene expression profiling from formalin-fixed paraffin-embedded (FFPE) renal allograft biopsies is a promising approach for feasibly providing a molecular diagnosis of rejection. However, large-scale studies evaluating the performance of models using NanoString platform data to define molecular archetypes of rejection are lacking. We tested a diverse retrospective cohort of over 1400 FFPE biopsy specimens, rescored according to Banff 2019 criteria and representing 10 of 11 United Network of Organ Sharing regions, using the Banff Human Organ Transplant panel from NanoString and developed a multiclass model from the gene expression data to assign relative probabilities of 4 molecular archetypes: No Rejection, Antibody-Mediated Rejection, T Cell-Mediated Rejection, and Mixed Rejection. Using Least Absolute Shrinkage and Selection Operator regularized regression with 10-fold cross-validation fitted to 1050 biopsies in the discovery cohort and technically validated on an additional 345 biopsies, our model achieved overall accuracy of 85% in the discovery cohort and 80% in the validation cohort, with ≥75% positive predictive value for each class, except for the Mixed Rejection class in the validation cohort (positive predictive value, 53%). This study represents the technical validation of the first model built from a large and diverse sample of diagnostic FFPE biopsy specimens to define and classify molecular archetypes of histologically defined diagnoses as derived from Banff Human Organ Transplant panel gene expression profiling data.
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Affiliation(s)
| | | | | | | | | | - Jon Wilson
- Arkana Laboratories, Little Rock, Arkansas
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Ahangaran M, Sun E, Le K, Sun J, Wang WM, Tan TH, Burdine LJ, Dvanajscak Z, Cassol CA, Sharma S, Kolachalama VB. A web-based tool for real-time adequacy assessment of kidney biopsies. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.02.01.24302147. [PMID: 38370740 PMCID: PMC10871452 DOI: 10.1101/2024.02.01.24302147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2024]
Abstract
The escalating incidence of kidney biopsies providing insufficient tissue for diagnosis poses a dual challenge, straining the healthcare system and jeopardizing patients who may require rebiopsy or face the prospect of an inaccurate diagnosis due to an unsampled disease. Here, we introduce a web-based tool that can provide real-time, quantitative assessment of kidney biopsy adequacy directly from photographs taken with a smartphone camera. The software tool was developed using a deep learning-driven automated segmentation technique, trained on a dataset comprising nephropathologist-confirmed annotations of the kidney cortex on digital biopsy images. Our framework demonstrated favorable performance in segmenting the cortex via 5-fold cross-validation (Dice coefficient: 0.788±0.130) (n=100). Offering a bedside tool for kidney biopsy adequacy assessment has the potential to provide real-time guidance to the physicians performing medical kidney biopsies, reducing the necessity for re-biopsies. Our tool can be accessed through our web-based platform: http://www.biopsyadequacy.org.
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Affiliation(s)
- Meysam Ahangaran
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - Emily Sun
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - Khang Le
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - Jiawei Sun
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - William M. Wang
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - Tian Herng Tan
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - Lyle J. Burdine
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, US
| | | | | | | | - Vijaya B. Kolachalama
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
- Department of Computer Science, Boston University, Boston, MA, USA; Faculty of Computing & Data Sciences, Boston University, Boston, MA, USA
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14
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Pavlakou P, Gakiopoulou H, Djudjaj S, Palamaris K, Trivyza MS, Stylianou K, Goumenos DS, Papachristou E, Papasotiriou M. Keratin Expression in Podocytopathies, ANCA-Associated Vasculitis and IgA Nephropathy. Int J Mol Sci 2024; 25:1805. [PMID: 38339083 PMCID: PMC10855225 DOI: 10.3390/ijms25031805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/25/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024] Open
Abstract
Keratins are the main components of the cell cytoskeleton of epithelial cells. Epithelial cells under stressful stimuli react by modifying their keratin expression pattern. Glomerular diseases are pathological conditions that may lead to loss of kidney function if not timely diagnosed and treated properly. This study aims to examine glomerular and tubular keratin expression in podocytopathies, ANCA-associated vasculitis, and IgA nephropathy and how this expression correlates to clinical outcomes. We included 45 patients with podocytopathies (minimal change disease and focal segmental glomerulosclerosis), ANCA-associated vasculitis, and IgA nephropathy, with or without crescentic lesions, and healthy controls. All tissues were assessed by photon microscopy and immunohistochemistry. Biopsy sections were examined for keratins 7, 8, 18, and 19 expression in the glomerular and tubulointerstitial areas separately. Moreover, we examined how keratin expression was correlated with long-term kidney function outcomes. All four studied keratins had significantly increased glomerular expression in patients with ANCA vasculitis compared to controls and MCD patients. Tubular expression of keratins 7, 8, and 19 was related to kidney outcome in all groups. Patients with crescents had higher expression of all keratins in both glomeruli and tubulointerstitium. The presence of tubular atrophy, interstitial fibrosis, mesangial hyperplasia, and interstitial inflammation did not affect keratin expression. Keratins, an abundant component of renal epithelial cells, have the potential to be featured as a biomarker for kidney function prognosis in patients with glomerular diseases.
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Affiliation(s)
- Paraskevi Pavlakou
- Department of Nephrology and Kidney Transplantation, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (M.S.T.); (D.S.G.); (E.P.)
| | - Harikleia Gakiopoulou
- 1st Department of Pathology, National and Kapodistrian University of Athens Medical School, 34400 Athens, Greece
| | - Sonja Djudjaj
- Institute of Pathology, RWTH University of Aachen, 52074 Aachen, Germany
| | - Kostas Palamaris
- 1st Department of Pathology, National and Kapodistrian University of Athens Medical School, 34400 Athens, Greece
| | - Maria Stella Trivyza
- Department of Nephrology and Kidney Transplantation, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (M.S.T.); (D.S.G.); (E.P.)
| | - Kostas Stylianou
- Department of Nephrology, University Hospital of Heraklion, 71500 Heraklion, Greece;
| | - Dimitrios S. Goumenos
- Department of Nephrology and Kidney Transplantation, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (M.S.T.); (D.S.G.); (E.P.)
| | - Evangelos Papachristou
- Department of Nephrology and Kidney Transplantation, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (M.S.T.); (D.S.G.); (E.P.)
| | - Marios Papasotiriou
- Department of Nephrology and Kidney Transplantation, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (M.S.T.); (D.S.G.); (E.P.)
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15
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Sharma P, Shah R, Zavaletta V, Bertino F, Sankhla T, Kim JM, Leshen M, Shah J. Pediatric Transplant Interventions. Tech Vasc Interv Radiol 2023; 26:100930. [PMID: 38123288 DOI: 10.1016/j.tvir.2023.100930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
The field of pediatric organ transplantation has grown significantly in recent decades, with interventional radiology (IR) playing an essential role in managing pre and post-transplant complications. Pediatric transplant patients face unique challenges compared to adults, including donor-recipient size mismatch, and complications of a growing child with changing physiology. Interventional radiologists play a major role in pediatric renal and liver transplant. IR interventions begin early in the child's pretransplant journey, with diagnostic procedures such as biopsies, angiograms, and cholangiograms. These procedures are essential for understanding the etiology of organ failure and identifying potential transplant candidates. Minimally invasive therapeutic procedures may serve as bridges to transplant and may include vascular access optimization for hemodialysis, transjugular intrahepatic portosystemic shunts (TIPS) creation, and tumor embolization or ablation. After transplant, image-guided biopsies for the surveillance of graft rejection and treatment of vascular or luminal stenoses, pseudoaneurysms, and anastomotic leaks can maintain the function and longevity of the transplant organ. Careful consideration must be given to patient size and evolving anatomy, radiation exposure, and the need for deeper sedation for pediatric patients. Despite these challenges, the integration of IR in pediatric transplant care has proven beneficial, offering minimally invasive alternatives to surgery, faster recovery times, and improved outcomes.
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Affiliation(s)
- Pareena Sharma
- Medical College of Georgia, Augusta University, Augusta, GA
| | - Ritu Shah
- Seth G.S Medical College and K.E.M Hospital, Mumbai, Maharashtra, India
| | - Vaz Zavaletta
- Department of Radiology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO
| | - Frederic Bertino
- Department of Radiology, Interventional Radiology Section, NYU Langone Health/NYU Grossman School of Medicine, New York, NY
| | - Tina Sankhla
- Department of Radiology and Imaging Sciences, Division of Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, GA
| | - Jun Man Kim
- Department of Radiology and Imaging Sciences, Division of Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, GA
| | - Michael Leshen
- Department of Radiology, Division of Interventional Radiology, Children's Healthcare of Atlanta, Atlanta, GA
| | - Jay Shah
- Department of Radiology, Division of Interventional Radiology, Children's Healthcare of Atlanta, Atlanta, GA; Department of Radiology and Imaging Sciences, Division of Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, GA.
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16
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Ivković V, Bajema IM, Kronbichler A. Beyond Serology: Is There Still a Value of Kidney Biopsy in Anti-Glomerular Basement Membrane Disease? Kidney Int Rep 2023; 8:2495-2498. [PMID: 38106597 PMCID: PMC10719590 DOI: 10.1016/j.ekir.2023.10.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 10/10/2023] [Indexed: 12/19/2023] Open
Affiliation(s)
- Vanja Ivković
- Department of Internal Medicine, Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Croatia
- University of Rijeka Faculty of Health Studies, Rijeka, Croatia
| | - Ingeborg M. Bajema
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center, Groningen, The Netherlands
| | - Andreas Kronbichler
- Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Austria
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17
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Schaub JA, O'Connor CL, Dailey M, Hlynka AW, Chang Y, Postiff D, Kaffenberger SD, Palapattu GS, Gillespie BW, Hodgin JB, Shedden K, Bitzer M. Spatial Heterogeneity of Glomerular Phenotypes Affects Kidney Biopsy Findings. KIDNEY360 2023; 4:1598-1607. [PMID: 37889598 PMCID: PMC10695647 DOI: 10.34067/kid.0000000000000283] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 10/11/2023] [Indexed: 10/29/2023]
Abstract
Key Points Glomeruli with pathologic changes are not homogeneously distributed throughout the kidney cortex. Biopsies that do not include the kidney capsule may underdetect glomeruli with pathologic changes. Location of glomeruli with pathologic changes may be related to underlying clinical characteristics. Background Detection of rare glomerular phenotypes can affect diagnosis in indication kidney biopsies and in kidney tissue used for research studies. Nephropathologists are aware of potential sampling error when assessing needle biopsy cores, but quantitative data are lacking. Methods Kidney tissue from patients undergoing total nephrectomy enrolled in an observational, cross-sectional cohort study was used to characterize glomeruli as typical or atypical, which included globally sclerotic glomeruli (GSGs), segmentally sclerotic glomeruli, ischemic-like, and imploding. A 2D map of the glomerular annotations was generated. Spatial centrality of atypical glomeruli using the L2 metric and differences in pairwise distances between typical or atypical glomeruli were calculated. To determine how the yield of capturing atypical glomerular phenotype was affected by biopsy depth (i.e. , not including the renal capsule), simulated kidney biopsies were generated from the 2D map. Results The mean number of glomeruli in a nephrectomy specimen was 209 (SD 143), and GSGs were the most common type of atypical glomeruli (median: 13% [interquartile range: 5,31]). Typical glomeruli were more likely to be surrounded by other glomeruli (i.e. , centrally located in the kidney cortex) than GSGs, segmentally sclerosed glomeruli, ischemic-like glomeruli, and imploding glomeruli. Atypical glomeruli were 7.3% (95% confidence interval, 4.1 to 10.4) closer together than typical glomeruli and were more likely to be closer together in older patients or those with hypertension. In simulated kidney biopsies, failure to capture the capsule was associated with underdetection of GSGs, ischemic-like glomeruli, and imploding glomeruli. Conclusions Spatial analysis of large sections of kidney tissue provided quantitative evidence of spatial heterogeneity of glomerular phenotypes including clustering of atypical glomeruli in individuals with hypertension or older age. Most importantly, deep kidney biopsies that lack subcapsular area underdetect atypical glomerular phenotypes, suggesting that capturing the renal capsule is an important quality control measure for kidney biopsies.
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Affiliation(s)
- Jennifer A. Schaub
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | | | - Meghan Dailey
- Advanced Research Computing (Information and Technology Services), University of Michigan, Ann Arbor, Michigan
| | | | - Yurui Chang
- Department of Statistics, University of Michigan, Ann Arbor, Michigan
| | - Deborah Postiff
- Department of Pathology, University of Michigan, Ann Arbor, Michigan
| | | | | | - Brenda W. Gillespie
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan
| | - Jeffrey B. Hodgin
- Department of Pathology, University of Michigan, Ann Arbor, Michigan
| | - Kerby Shedden
- Department of Statistics, University of Michigan, Ann Arbor, Michigan
| | - Markus Bitzer
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
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18
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Schnuelle P. Renal Biopsy for Diagnosis in Kidney Disease: Indication, Technique, and Safety. J Clin Med 2023; 12:6424. [PMID: 37835066 PMCID: PMC10573674 DOI: 10.3390/jcm12196424] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 09/29/2023] [Accepted: 10/04/2023] [Indexed: 10/15/2023] Open
Abstract
Renal biopsies are the gold standard for diagnosis, staging, and prognosis of underlying parenchymal kidney disease. This article provides an overview of the current indications and highlights ways to reduce bleeding complications in order to achieve optimal diagnostic yield with minimal risk to the patient. Novel indications have emerged from the increasing use of new molecularly targeted oncologic therapies in recent years, which often induce immune-mediated renal disease. On the other hand, the detection of specific antibodies against target antigens on podocytes in the sera of patients with new-onset nephrotic syndrome has now relativized the indication for biopsy in membranous nephropathy. The use of semi-automatic spring-loaded biopsy devices and real-time ultrasound considerably declined the complication rate and is the current standard. Percutaneous renal biopsies are overall a safe procedure if contraindications are considered. A coagulation disorder needs to be excluded beforehand, and an elevated blood pressure must be reduced to the normotensive range with medications. A laparoscopic approach or a radiology interventional procedure through the internal jugular vein may be considered for obtaining a kidney tissue sample if there is an urgent indication and a bleeding tendency cannot be adequately corrected. Major bleeding after a percutaneous renal biopsy can usually be managed with selective arterial embolization of the injured renal vessel. The use of a 16-gauge needle is the most reasonable compromise between diagnostic benefit and risk of complication. In the routine diagnostic, the biopsy specimen is examined with light microscopy, immunohistochemistry, and electron microscopy. Combination with modern molecular pathology techniques will contribute to more precise insights into the development and progression of kidney disease, which will likely refine future treatments in nephrology.
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Affiliation(s)
- Peter Schnuelle
- Center for Renal Diseases Weinheim, Academic Teaching Practice of the University Medical Center Mannheim, University of Heidelberg, D-69469 Weinheim, Germany
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19
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Kalra S, Mukund B, Kumar M, Kanitkar M. Comparative analysis of blind vs real-time ultrasound-guided pediatric renal biopsies: A cross-sectional study. Med J Armed Forces India 2023; 79:409-413. [PMID: 37441299 PMCID: PMC10334249 DOI: 10.1016/j.mjafi.2021.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 05/14/2021] [Indexed: 11/20/2022] Open
Abstract
Background Renal biopsy has a definite role in the management of pediatric kidney diseases. Most centers have given up the earlier practice of performing blind biopsy using Tru-Cut needle and started doing real time ultrasound-guided renal biopsy with an automated spring-loaded gun, which has become standard of care in the last decade or so. Methods We performed a cross-sectional analysis of the pediatric biopsies conducted at our center over the years by both methods to evaluate whether ultrasound-guided renal biopsy with a disposable automated spring-loaded gun was superior to blind biopsy with a disposable needle of the same size in terms of reduction of complications and improving the yield. We also reviewed the indications and the histopathological diagnosis of pediatric renal biopsies at our center. Results A total of 45 native kidney biopsies were performed blind and 48 ultrasound-guided biopsies using the curvilinear probe (frequency 3-5 Hz) of GE Logiq P3 ultrasound machine with disposable spring-loaded automated guns. There was a significant increase in the yield of biopsy in terms of the number of glomeruli per pass. A significant increase in the mean number of glomeruli was noted when a biopsy was performed under ultrasound guidance (P < 0.0001). Gross hematuria was significantly reduced as compared to the earlier biopsies done blind i.e., without ultrasound (P ¼ 0.03). Nephrotic syndrome was the commonest indication for biopsy in our patients during both time periods studied. The most common histopathological diagnosis was MesPGN among the children who underwent kidney biopsy from 2005 to 2007, while Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) were most frequently reported. Conclusion Ultrasound guided kidney biopsies in pediatric age group have significant reduction in incidence of post gross hematuria and significant increase in the mean number of glomeruli per pass.
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Affiliation(s)
- Suprita Kalra
- Classified Specialist & Associate Professor (Pediatrics), Army Hospital (R&R), Delhi Cantt, India
| | - Bal Mukund
- Classified Specialist & Associate Professor (Pediatrics), INHS Kalyani, Vishakapatnam, India
| | - Mritunjay Kumar
- Associate Professor (Pediatrics), AIIMS, Raebareli, UP, India
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20
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Jensen MS, Merrild C, Nørregaard R, Olinga P, Mutsaers HAM. Standardized Protocol for the Preparation of Precision-Cut Kidney Slices: A Translational Model of Renal Fibrosis. Methods Mol Biol 2023; 2664:123-134. [PMID: 37423986 DOI: 10.1007/978-1-0716-3179-9_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/11/2023]
Abstract
Renal fibrosis is a hallmark of progressive renal diseases. To date, there is a lack of effective therapeutics for the treatment of renal fibrosis, in part due to the scarcity of clinically relevant translational disease models. Since the early 1920s, hand-cut tissue slices have been used as a means to better understand organ (patho)physiology in a variety of scientific fields. From that time, the equipment and methodology for the preparation of tissue slices has continuously improved, thereby expanding the applicability of the model. Nowadays, precision-cut kidney slices (PCKS) have been demonstrated to be an extremely valuable translation model for renal (patho)physiology, bridging the gap between preclinical and clinical research. A key feature of PCKS is that the slices contain all cell types and acellular components of the whole organ in the original configuration while preserving cell-cell and cell-matrix interactions. In this chapter, we describe how to prepare PCKS and how the model can be implemented in fibrosis research.
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Affiliation(s)
| | - Camilla Merrild
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Rikke Nørregaard
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Peter Olinga
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
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21
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HFANet: hierarchical feature fusion attention network for classification of glomerular immunofluorescence images. Neural Comput Appl 2022. [DOI: 10.1007/s00521-022-07676-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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22
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Zhao R, Wu Y, Shen X, Jian D, Fu L, Liu H, Zhai Y, Chen J, Shen Q, Xu H, Gu Y, Zhou Q. A Therapeutic Play Program for Children Undergoing Kidney Biopsy With Local Anesthesia: Construction and Feasibility Evaluation. J Perianesth Nurs 2022; 37:939-945. [PMID: 36153207 DOI: 10.1016/j.jopan.2022.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 04/06/2022] [Accepted: 04/24/2022] [Indexed: 11/16/2022]
Abstract
PURPOSE To construct a therapeutic play program for children undergoing preparation for kidney biopsy under local anesthesia and explore the feasibility of the program from stakeholders' perspectives. DESIGN The program was constructed by a multidisciplinary team and the feasibility and acceptability of the program were explored by a descriptive qualitative study. METHODS Based on Lazarus & Folkman's stress-coping model and Piaget's theory of play, and using on-site participatory field observation, a multidisciplinary team constructed a therapeutic play program for children undergoing kidney biopsy under local anesthesia. The feasibility and acceptability of the program were evaluated by interviewing children, their caregivers, and physicians. FINDINGS The main tools constructed for the intervention were a 15-page picture book titled Kidney Biopsy Treasure Hunt and a homemade kidney biopsy play package. The therapeutic play intervention for kidney biopsy under local anesthesia was led by nurses and followed the steps of kidney biopsy, using the picture book, and group play simulation. Through informed in-depth interviews with 10 children and their caregivers, we showed that the therapeutic play program materials were accessible, clinically feasible, and necessary for kidney biopsy under local anesthesia in children. The children and their caregivers had high acceptance of the content of the picture book, the format of the play, and high satisfaction with the overall program. CONCLUSIONS The therapeutic play program we constructed for children undergoing kidney biopsy with local anesthesia was simple, feasible, and well accepted in the clinical setting.
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Affiliation(s)
- Rui Zhao
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Yuanyuan Wu
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Xia Shen
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Duying Jian
- Department of Social Work, Children's Hospital of Fudan University, Shanghai, China
| | - Lili Fu
- Department of Social Work, Children's Hospital of Fudan University, Shanghai, China
| | - Haimei Liu
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Yihui Zhai
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Jing Chen
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Qian Shen
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Hong Xu
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Ying Gu
- Nursing Department, Children's Hospital of Fudan University, Shanghai, China
| | - Qing Zhou
- Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
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23
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Safabakhsh S, Sar F, Martelotto L, Haegert A, Singhera G, Hanson P, Parker J, Collins C, Rohani L, Laksman Z. Isolating Nuclei From Frozen Human Heart Tissue for Single-Nucleus RNA Sequencing. Curr Protoc 2022; 2:e480. [PMID: 35816165 DOI: 10.1002/cpz1.480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Heart disease is the leading cause of global morbidity and mortality. This is in part because, despite an abundance of animal and in vitro models, it has been a challenge to date to study human heart tissue with sufficient depth and resolution to develop disease-modifying therapies for common cardiac conditions. Single-nucleus RNA sequencing (snRNA-seq) has emerged as a powerful tool capable of analyzing cellular function and signaling in health and disease, and has already contributed to significant advances in areas such as oncology and hematology. Employing snRNA-seq technology on flash-frozen human tissue has the potential to unlock novel disease mechanisms and pathways in any organ. Studying the human heart using snRNA-seq is a key priority for the field of cardiovascular sciences; however, progress to date has been slowed by numerous barriers. One key challenge is the fact that the human heart is very resistant to shearing and stress, making tissue dissociation and nuclear isolation difficult. Here, we describe a tissue dissociation method allowing the efficient and cost-effective isolation of high-quality nuclei from flash-frozen human heart tissue collected in surgical operating rooms. Our protocol addresses the challenge of nuclear isolation from human hearts, enables snRNA-seq of the human heart, and paves the way for an improved understanding of the human heart in health and disease. Ultimately, this will be key to uncovering signaling pathways and networks amenable to therapeutic intervention and the development of novel biomarkers and disease-modifying therapies. © 2022 Wiley Periodicals LLC. Basic Protocol: Human heart tissue dissociation and nuclear isolation for snRNA-seq.
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Affiliation(s)
- Sina Safabakhsh
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Funda Sar
- Vancouver Prostate Centre, UBC, Vancouver, British Columbia, Canada
| | | | - Anne Haegert
- Vancouver Prostate Centre, UBC, Vancouver, British Columbia, Canada
| | | | | | - Jeremy Parker
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Colin Collins
- Vancouver Prostate Centre, UBC, Vancouver, British Columbia, Canada
| | - Leili Rohani
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Zachary Laksman
- University of British Columbia, Vancouver, British Columbia, Canada
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So WZ, Teo RZC, Ooi LY, Goh BYS, Lu J, Vathsala A, Thamboo TP, Tiong HY. Multi-photon microscopy for the evaluation of interstitial fibrosis in extended criteria donor kidneys: A Proof-of-Concept Study. Clin Transplant 2022; 36:e14717. [PMID: 35598116 DOI: 10.1111/ctr.14717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 05/14/2022] [Accepted: 05/16/2022] [Indexed: 11/03/2022]
Abstract
INTRODUCTION To evaluate the initial use of label-free second harmonic generation (SHG) imaging with two-photon excitation (2PE) auto-fluorescence in multi-photon microscopy (MPM) for the quantification of collagen/fibrosis on pre-implantation biopsies of extended criteria donors (ECD). MATERIALS AND METHODS 20 pre-implantation core biopsies were extracted from 10 donor kidney samples, of which originated from 7 donors. Kidney Donor Profile Index (KDPI) and Remuzzi scores of biopsies were calculated. Collagen parameters measured included quantification by the Collagen Area Ratio in Total Tissue (CART) and qualitative measurements by Collagen Reticulation Index (CRI). RESULTS Biopsies classified with > 85% KDPI scores had significantly higher CART (p = 0.011) and lower CRI values (p = 0.025) than biopsies with ≤ 85% KDPI scores. Increase in CRI values correlated significantly with rise in recipient creatinine levels 1-year post-transplant (p = 0.027; 95% CI: 4.635-66.797). CONCLUSION MPM is an evolving technology that enables the quantification of the amount (CART) and quality (CRI) of collagen deposition in unstained pre-implantation biopsies of donor kidneys stratified by KDPI scores. This initial evaluation found significant differences in both parameters between donor kidneys with more or less than 85% KDPI. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Wei Zheng So
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Rachel Zui Chih Teo
- Division of Nephrology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Li Yin Ooi
- Department of Pathology, National University Hospital, Singapore, Singapore
| | - Benjamin Yen Seow Goh
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Department of Urology, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
| | - Jirong Lu
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Department of Urology, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
| | - Anantharaman Vathsala
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Nephrology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
| | - Thomas Paulraj Thamboo
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Nephrology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Ho Yee Tiong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Department of Urology, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
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Olsen E, van Galen G. Chronic Renal Failure-Causes, Clinical Findings, Treatments and Prognosis. Vet Clin North Am Equine Pract 2022; 38:25-46. [DOI: 10.1016/j.cveq.2021.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Young J, Shahedi M, Dormer JD, Johnson B, Gahan J, Fei B. A low-cost PVC-based dual-modality kidney phantom. PROCEEDINGS OF SPIE--THE INTERNATIONAL SOCIETY FOR OPTICAL ENGINEERING 2022; 12034:120342Q. [PMID: 36793656 PMCID: PMC9928528 DOI: 10.1117/12.2611592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Phantoms are invaluable tools broadly used for research and training purposes designed to mimic tissues and structures in the body. In this paper, polyvinyl chloride (PVC)-plasticizer and silicone rubbers were explored as economical materials to reliably create long-lasting, realistic kidney phantoms with contrast under both ultrasound (US) and X-ray imaging. The radiodensity properties of varying formulations of soft PVC-based gels were characterized to allow adjustable image intensity and contrast. Using this data, a phantom creation workflow was established which can be easily adapted to match radiodensity values of other organs and soft tissues in the body. Internal kidney structures such as the medulla and ureter were created using a two-part molding process to allow greater phantom customization. The kidney phantoms were imaged under US and X-ray scanners to compare the contrast enhancement of a PVC-based medulla versus a silicone-based medulla. Silicone was found to have higher attenuation than plastic under X-ray imaging, but poor quality under US imaging. PVC was found to exhibit good contrast under X-ray imaging and excellent performance for US imaging. Finally, the durability and shelf life of our PVC-based phantoms were observed to be vastly superior to that of common agar-based phantoms. The work presented here allows extended periods of usage and storage for each kidney phantom while simultaneously preserving anatomical detail, contrast under dual-modality imaging, and low cost of materials.
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Affiliation(s)
- Jeff Young
- Department of Bioengineering, The University of Texas at Dallas, TX
| | - Maysam Shahedi
- Department of Bioengineering, The University of Texas at Dallas, TX
- Center for Imaging and Surgical Innovation, The University of Texas at Dallas, TX
| | - James D. Dormer
- Department of Bioengineering, The University of Texas at Dallas, TX
- Center for Imaging and Surgical Innovation, The University of Texas at Dallas, TX
| | - Brett Johnson
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX
| | - Jeffrey Gahan
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX
| | - Baowei Fei
- Department of Bioengineering, The University of Texas at Dallas, TX
- Center for Imaging and Surgical Innovation, The University of Texas at Dallas, TX
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX
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Relationship between glomerular number in fresh kidney biopsy samples and light microscopy samples. Clin Exp Nephrol 2022; 26:424-434. [PMID: 35103876 DOI: 10.1007/s10157-022-02179-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 01/03/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND On-site evaluation of fresh kidney biopsy (FKB) samples at the time of biopsy is useful to verify that adequate specimens are acquired. However, some cases present poor correlation between glomerular number in FKB samples and light microscopy (LM) samples. We examined the usefulness of such on-site evaluation. METHODS We conducted a retrospective cross-sectional observational study (n = 129) to assess the correlation between glomerular number in FKB samples and LM samples and the associated factors hindering the evaluation. RESULTS There was a significant positive correlation between glomerular number in FKB samples and LM samples. The median ratio of glomerular number (LM samples/FKB samples) was 0.74. According to this ratio, cases were divided into three groups: reasonable estimation (65 cases), underestimation (32 cases), and overestimation (32 cases). Comparing the reasonable and underestimation groups, significant differences were detected in the extent of interstitial fibrosis and tubular atrophy (IFTA) and interstitial inflammation. Logistic regression analysis demonstrated that IFTA and interstitial inflammation were significantly associated with the underestimation. Moreover, the cortex length of FKB samples correlated with glomerular number in LM samples regardless of tubulointerstitial lesions. CONCLUSIONS Glomerular number determined during on-site evaluation can be a reference for the actual number of glomeruli in LM samples. Since tubulointerstitial lesions make it difficult to recognize glomeruli in FKB samples, the possibility of underestimation for cases with possibly severe tubulointerstitial lesions should be considered. In such cases, evaluation of cortex length of FKB samples may substitute for evaluating glomeruli on-site.
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Increasing Incidence of Inadequate Kidney Biopsy Samples Over Time: A 16-Year Retrospective Analysis From a Large National Renal Biopsy Laboratory. Kidney Int Rep 2022; 7:251-258. [PMID: 35155864 PMCID: PMC8820989 DOI: 10.1016/j.ekir.2021.11.026] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 11/22/2021] [Indexed: 11/23/2022] Open
Abstract
Introduction Renal biopsy remains an essential tool for the diagnosis and treatment of patients with medical kidney disease. Recently, there has been a perceived change in the number of inadequate samples. The aim of this study was to determine the native renal biopsy miss rate from 2005 to 2020 at Arkana Laboratories, a nationwide kidney biopsy service. Methods From 2005 to 2020, a total of 123,372 native kidney biopsies were received from >2500 nephrologists practicing across 44 US states. The miss rate was determined by age and year. In a subset of biopsies received in 2005 and 2018, the biopsy operator was determined, nephrologist or radiologist. Furthermore, the miss rate, needle gauge, biopsy depth by operator, and biopsy core width by gauge were measured. Results The miss rate increased markedly from 2% in 2005 to 14% in 2020. Radiologists performed 5% of biopsies in 2005 and 95% in 2018 using smaller diameter (18g/20g) needles 92% of the time. Glomeruli per centimeter of core biopsy and mean core width were significantly lower with smaller needles. The miss rate deep was significantly lower for nephrologists and remained consistent within operator between the 2 time points. The miss rate did not correlate with the increasing age of the population who had biopsies. Conclusion This increase in kidney biopsy miss rate significantly affects patient care in the management of medical kidney disease. Its correlation with the complete reversal in operators suggests an urgent need for interaction with and training of radiologists in this critical technique.
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Kidney biopsy adequacy and complications in children - does technique matter? Eur J Pediatr 2022; 181:2677-2684. [PMID: 35414029 PMCID: PMC9192435 DOI: 10.1007/s00431-022-04464-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 03/30/2022] [Accepted: 03/31/2022] [Indexed: 12/04/2022]
Abstract
UNLABELLED Kidney biopsy is part of the diagnostic workup of many children with renal disease. Traditionally, a perpendicular approach to the biopsy has been used, but more recently, some proceduralists have favoured a tangential approach. It is not clear if one technique is superior with regards to tissue adequacy or complication rates. In our centre, interventional radiologists (IR) use general anaesthetic and a tangential approach, whereas paediatric nephrologists (PN) use sedation and a perpendicular approach. We examined consecutive native kidney biopsies performed between January 2008 and December 2017 for adequacy (sufficient tissue for light and electron microscopy and immunofluorescence) and examined the electronic medical records for data regarding technique and complications. IR performed 72 (29%) of the 245 native kidney biopsies, obtaining more total glomeruli (median 39 vs 16, p < 0.001) and more glomeruli per tissue core (median 13 vs 8, p < 0.001) than PN. No differences in specimen adequacy were observed between the two groups (79% IR vs 81% PN, p = 0.75) and a diagnosis could be made in 99% and 94% respectively (p = 0.1). A statistically lower rate of peri-nephric haematoma (28% vs 42%, p = 0.04) was detected in the IR group, but there were no significant differences in other complications. One patient required a blood transfusion (PN) and another required surgical intervention for a perinephric haematoma (IR). CONCLUSION IR obtained larger samples and number of glomeruli, but the overall adequacy for native kidney biopsies was good using both perpendicular and tangential techniques, with low rates of significant complications. WHAT IS KNOWN • Kidney biopsy is integral to the diagnostic work-up of many children with kidney disease. • Kidney biopsy is a safe procedure with well-established complications in a minority of children. WHAT IS NEW • Interventional radiologists had higher biopsy yield than paediatric nephrologists, possibly due to the tangential approach. • Biopsy adequacy rates are high using both techniques and provided a diagnosis in over 95% of cases.
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Abstract
The medical kidney biopsy has an important added value in patient care in nephrology. In order to facilitate communication between the pathologist and the nephrologist and optimize patient care, both the content and form of the medical kidney biopsy report matter. With some exceptions, current guidelines in nephropathology focus on content rather than form and, not surprisingly, medical kidney biopsy reports mostly consist of unformatted and often lengthy free text. In contrast, in oncology, a more systematic reporting called synoptic reporting has become the dominant method. Synoptic formats enable complete, concise and clear reports that comply with agreed upon standards. In this review we discuss the possibilities of systematic reporting in nephropathology (including synoptic reporting). Furthermore, we explore applications of electronic formats with structured data and usage of international terminologies or coding systems. The benefits include the timely collection of high-quality data for benchmarking between centres as well as for epidemiologic and other research studies. Based on these developments, a scenario for future medical kidney biopsy reporting is drafted.
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Affiliation(s)
- Sabine Leh
- Department of Pathology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Amélie Dendooven
- Department of Pathology, University Hospital Ghent, Ghent, Belgium
- Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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Abstract
Immunofluorescence is an important immunochemical technique that utilizes fluorescence-labeled antibodies to detect specific target antigens. It is used widely in both scientific research and clinical laboratories. Immunofluorescence allows for excellent sensitivity and amplification of signal in comparison to immunohistochemistry. However, analysis of samples labeled with fluorescence-labeled antibodies has to be performed using a fluorescence microscope or other type of fluorescence imaging. There are two methods available: direct (primary) and indirect (secondary) immunofluorescence. Here, we describe the principle of immunofluorescence methods as well as the preparation of fresh-frozen and formalin-fixed, paraffin embedded tissues for both direct and indirect immunofluorescence labeling.
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Affiliation(s)
| | | | - Sergio Piña-Oviedo
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
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Kline A, Chung HJ, Rahmani W, Chun J. Semi-Supervised Segmentation of Renal Pathology: An Alternative to Manual Segmentation and Input to Deep Learning Training. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2021; 2021:2688-2691. [PMID: 34891805 DOI: 10.1109/embc46164.2021.9630248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Kidney biopsy interpretation is the gold standard for the diagnosis and prognosis for kidney disease. Pathognomonic diagnosis hinges on the correct assessment of different structures within a biopsy that is manually visualized and interpreted by a renal pathologist. This laborious undertaking has spurred attempts to automate the process, offloading the consumption of temporal resources. Segmentation of kidney structures, specifically, the glomeruli, tubules, and interstitium, is a precursory step for disease classification problems. Translating renal disease decision making into a deep learning model for diagnostic and prognostic classification also relies on adequate segmentation of structures within the kidney biopsy. This study showcases a semi-automated segmentation technique where the user defines starting points for glomeruli in kidney biopsy images of both healthy normal and diabetic kidney disease stained with Nile Red that are subsequently partitioned into four areas: background, glomeruli, tubules and interstitium. Five of 30 biopsies that were segmented using the semi-automated method were randomly selected and the regions of interest were compared to the manual segmentation of the same images. Dice Similarity Coefficients (DSC) between the methods showed excellent agreement; Healthy (glomeruli: 0.92, tubules: 0.86, intersititium: 0.78) and diabetic nephropathy: (glomeruli: 0.94, tubules: 0.80, intersititium: 0.80). To our knowledge this is the first semi-automated segmentation algorithm performed with human renal biopsies stained with Nile Red. Utility of this methodology includes further image processing within structures across disease states based on biological morphological structures. It can also be used as input into a deep learning network to train semantic segmentation and input into a deep learning algorithm for classification of disease states.
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Gu YZ, Handt L, Vlasakova K, Bakthavatchalu V, Smith R, Fernandez GE, Born SL, Glaab WE, Sistare FD. Kidney Injury Monitoring in Tobramycin-Treated Rhesus Monkeys: Supplementing Urinary Kidney Biomarkers With Kidney Biopsy Gene Expression Profiling. Toxicol Pathol 2021; 50:35-46. [PMID: 34657537 DOI: 10.1177/01926233211049171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Kidney biopsies are used sparingly to diagnose kidney injury in the clinic. Here we have conducted a small exploratory study to directly compare the low-grade kidney injury monitoring performance of serum safety biomarkers, novel urine safety biomarkers, microscopic histopathology and targeted gene expression alterations in kidney biopsy specimens in rhesus monkeys treated with tobramycin. Targeted gene expression increases were observed in the kidney biopsy samples and whole kidney sections for kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN) messenger RNA transcripts. In addition, increases of the urinary kidney safety protein biomarkers including KIM-1, CLU, OPN were also observed. These increases in gene expression and urinary protein end point were in concordance with the eventual low-grade kidney lesions seen in terminal tissue sections. In contrast, conventional serum biomarkers blood urea nitrogen and serum creatinine were not as sensitive in monitoring kidney injury. Although these data do not support routinely adding kidney biopsies to regular toxicology studies, they provide evidence on the value and limitations of incorporating gene expression profiling on kidney biopsy specimens, further underscore the value of urinary kidney safety biomarkers for improved low-grade kidney injury monitoring, and open the door for future definitive studies.
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Affiliation(s)
- Yi-Zhong Gu
- Safety Assessment and Laboratory Animal Resources, 2793Merck & Co, Inc, West Point, PA, USA
| | - Larry Handt
- Safety Assessment and Laboratory Animal Resources, 2793Merck & Co, Inc, West Point, PA, USA
| | - Katerina Vlasakova
- Safety Assessment and Laboratory Animal Resources, 2793Merck & Co, Inc, West Point, PA, USA
| | | | - Roger Smith
- Safety Assessment and Laboratory Animal Resources, 2793Merck & Co, Inc, West Point, PA, USA
| | - Guillermo E Fernandez
- Safety Assessment and Laboratory Animal Resources, 2793Merck & Co, Inc, West Point, PA, USA
| | - Stephanie L Born
- Safety Assessment and Laboratory Animal Resources, 2793Merck & Co, Inc, West Point, PA, USA
| | - Warren E Glaab
- Safety Assessment and Laboratory Animal Resources, 2793Merck & Co, Inc, West Point, PA, USA
| | - Frank D Sistare
- Safety Assessment and Laboratory Animal Resources, 2793Merck & Co, Inc, West Point, PA, USA
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Rovin BH, Adler SG, Barratt J, Bridoux F, Burdge KA, Chan TM, Cook HT, Fervenza FC, Gibson KL, Glassock RJ, Jayne DR, Jha V, Liew A, Liu ZH, Mejía-Vilet JM, Nester CM, Radhakrishnan J, Rave EM, Reich HN, Ronco P, Sanders JSF, Sethi S, Suzuki Y, Tang SC, Tesar V, Vivarelli M, Wetzels JF, Floege J. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100:S1-S276. [PMID: 34556256 DOI: 10.1016/j.kint.2021.05.021] [Citation(s) in RCA: 1092] [Impact Index Per Article: 273.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022]
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Gunduz N, Buz A, Kabaalioglu A. Does Early Diabetic Kidney Damage Alter Renal Elasticity? An Ultrasound-Based, Two-Dimensional Shear Wave Elastography Study. Medeni Med J 2021; 36:209-216. [PMID: 34915678 PMCID: PMC8565583 DOI: 10.5222/mmj.2021.65021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Accepted: 08/30/2021] [Indexed: 11/05/2022] Open
Abstract
Objective Kidney damage caused by type 2 diabetes mellitus (T2DM) can reduce renal elasticity. Limited number of data exist indicating whether early kidney damage causes stiffening of renal tissue. This comparative study aims to assess kidney elasticity in T2DM patients with or without moderate albuminuria, using ultrasound-based two-dimensional shear wave velocity (2D-SWV) measurements. Methods Fifty-seven cases (40 T2D patients with stage 1 or 2 chronic kidney disease and 17 age- and sex-matched healthy controls) were included in this single-center prospective study. The T2DM patients were divided into those with moderate albuminuria (n=22) and those without albuminuria (n=18). Bilateral renal parenchymal 2D-SWV values were measured (separately) in the upper, middle, and lower kidney regions. Group data were compared using the t-test or Mann-Whitney-U test (whichever appropriate). Inter-observer agreement was assessed by deriving the intra-class correlation coefficient. Results There was no difference between the T2DM and control groups in terms of the median age [55.5 (50-62) vs. 55 (48.5-59.5) years, p=0.48] and sex ratio [18 (45%) males vs. 10 (58.8%) females, p=0.34]. The average regional 2D-SWV values were all similar between the groups (all p>0.05). The average 2D-SWV values were similar between the subgroups with and without albuminuria. The inter-observer agreement was good (intra-class correlation coefficient=0.66, 95% CI 0.19-0.88, p=0.006). Conclusion Kidney elasticity does not seem to be compromised in patients with diabetes and preserved estimated glomerular filtration rate with or without moderate albuminuria.
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Affiliation(s)
- Nesrin Gunduz
- Istanbul Medeniyet University, School of Medicine, Department of Radiology, Istanbul, Turkey
| | - Aysenur Buz
- Istanbul Medeniyet University, School of Medicine, Department of Radiology, Istanbul, Turkey
| | - Adnan Kabaalioglu
- Istanbul Medeniyet University, School of Medicine, Department of Radiology, Istanbul, Turkey
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[The relevance of electron microscopy in kidney biopsies to 21 st century pathology]. REVISTA ESPAÑOLA DE PATOLOGÍA : PUBLICACIÓN OFICIAL DE LA SOCIEDAD ESPAÑOLA DE ANATOMÍA PATOLÓGICA Y DE LA SOCIEDAD ESPAÑOLA DE CITOLOGÍA 2021; 54:234-241. [PMID: 34544553 DOI: 10.1016/j.patol.2021.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/18/2020] [Accepted: 01/20/2021] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Electron microscopy (EM) has been used in the study of renal biopsies for more than 5 decades; however, it is expensive and the possibility of restricting it to selected cases has been considered. This study aims to reevaluate the necessity for EM in the diagnosis of renal biopsies today. MATERIAL AND METHODS All renal biopsies taken between 2016 and 2019 with adequate light microscopy (LM), immunofluorescence (IF) and EM studies were included. The initial diagnosis (without EM) and the final diagnosis (with EM) was recorded. EM was considered necessary in cases in which the initial and final diagnoses did not concur, when diagnosis could not be made with LM and IF only or if the EM study revealed further clinically relevant findings. RESULTS A total of 621 biopsies were included, 498 (80.2%) of native kidneys and 123 (19.8%) of transplanted kidneys. In 115 cases (18.5%) EM had been deemed necessary for diagnosis; it was required more frequently in hereditary diseases (96.8%) and isolated hematuria (88.9%) but less often in nephrotic syndrome (6.7%) and renal transplant biopsy (5.7%) (p < 0.001). CONCLUSIONS EM was required in less than a fifth of renal biopsies, being more necessary in isolated hematuria and hereditary diseases and less so in nephrotic syndrome and in renal graft biopsies. These findings may prove useful as a guide to case selection protocols in which EM could be considered as a non-mandatory technique.
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Analysis of Glomerular IgG Subclasses Switch in Idiopathic Membranous Nephropathy Classified by Glomerular Phospholipase A2 Receptor Antigen and Serum Antibody. DISEASE MARKERS 2021; 2021:9965343. [PMID: 34497677 PMCID: PMC8421165 DOI: 10.1155/2021/9965343] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 08/10/2021] [Indexed: 11/24/2022]
Abstract
Background The role of IgG subclass in idiopathic membranous nephropathy (IMN) was unclarified. Recent study found IgG subtype switches from IgG1 to IgG4 in the early pathological stage in IMN. The profile of IgG subclass in phospholipase A2 receptor- (PLA2R-) related and PLA2R-unrelated IMN was unrevealed. Our study is aimed at testifying whether IgG subclass switch existed in PLA2R-related and PLA2R-unrelated IMN, respectively. Methods Our study retrospectively enrolled 157 Chinese patients with biopsy-confirmed IMN between September 2017 and November 2019. We measured glomerular PLA2R antigen and serum anti-PLA2R antibody to classify the patients into PLA2R-related (n = 132) and PLA2R-unrelated (n = 25) subgroup. We evaluated glomerular IgG subclass by immunofluorescence (IF) predominance. Our study defined IgG subclass deposition as predominant if the IF score was higher than the other three and ≥1 +, or as codominant if the IF intensity was equal to any other and ≥1 +. We explored the relationship between IF predominance of glomerular IgG subtype and electron microscopic (EM) stages of IMN. Results We did not find statistical difference of predominant or codominant rate (pre/co-rate) among EM stages in any subclass (P > 0.05). Pre/co-rate of IgG3 linearly associated with EM stage in total and PLA2R-related subgroup (P = 0.044, P = 0.013). PLA2R-related subgroup showed higher IgG4 intensity (2.1 ± 0.6 vs. 1.6 ± 0.7, P = 0.001) and pre/co-rate of IgG4 in stage 1 (97% vs. 57%, P = 0.015) than PLA2R-unrelated group. We found no difference of IgG subclass pre/co-rate in different EM stages or linear association between pre/co-rate of IgG1, IgG2, IgG4, and EM stages (P > 0.05). Conclusions Pre/co-rate of IgG3 declined with EM stage in total and PLA2R-related subgroup. We did not find IgG subclass switches from IgG1 to IgG4 in either IMN patients or subgroups.
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Caza TN, Hassen SI, Kenan DJ, Storey A, Arthur JM, Herzog C, Edmondson RD, Bourne TD, Beck LH, Larsen CP. Transforming Growth Factor Beta Receptor 3 (TGFBR3)-Associated Membranous Nephropathy. KIDNEY360 2021; 2:1275-1286. [PMID: 35369660 PMCID: PMC8676385 DOI: 10.34067/kid.0001492021] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 06/10/2021] [Indexed: 02/04/2023]
Abstract
Background Membranous lupus nephritis (MLN) comprises 10%-15% of lupus nephritis and increases morbidity and mortality of patients with SLE through complications of nephrotic syndrome and chronic kidney failure. Identification of the target antigens in MLN may enable noninvasive monitoring of disease activity, inform treatment decisions, and aid in prognostication, as is now possible for idiopathic MN caused by antibodies against the phospholipase A2 receptor. Here, we show evidence for type III TGF-β receptor (TGFBR3) as a novel biomarker expressed in a subset of patients with MLN. Methods Mass spectrometry was used for protein discovery through enrichment of glomerular proteins by laser capture microdissection and through elution of immune complexes within MLN biopsy specimens. Colocalization with IgG within glomerular immune deposits from patients and disease controls was evaluated by confocal microscopy. Immunostaining of consecutive case series was used to determine the overall frequency in MN and MLN. Results TGFBR3 was found to be enriched in glomeruli and coimmunoprecipitated with IgG within a subset of MLN biopsy specimens by mass spectrometry. Staining of consecutive MN cases without clinical evidence of SLE did not show TGFBR3 expression (zero of 104), but showed a 6% prevalence in MLN (11 of 199 cases). TGFBR3 colocalized with IgG along the glomerular basement membranes in TGFBR3-associated MN, but not in controls. Conclusions Positive staining for TGFBR3 within glomerular immune deposits represents a distinct form of MN, substantially enriched in MLN. A diagnosis of TGFBR3-associated MN can alert the clinician to search for an underlying autoimmune disease.
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Affiliation(s)
| | | | | | - Aaron Storey
- University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - John M Arthur
- University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Christian Herzog
- University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Rick D Edmondson
- University of Arkansas for Medical Sciences, Little Rock, Arkansas
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Deep learning-based transformation of H&E stained tissues into special stains. Nat Commun 2021; 12:4884. [PMID: 34385460 PMCID: PMC8361203 DOI: 10.1038/s41467-021-25221-2] [Citation(s) in RCA: 132] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 07/29/2021] [Indexed: 11/08/2022] Open
Abstract
Pathology is practiced by visual inspection of histochemically stained tissue slides. While the hematoxylin and eosin (H&E) stain is most commonly used, special stains can provide additional contrast to different tissue components. Here, we demonstrate the utility of supervised learning-based computational stain transformation from H&E to special stains (Masson's Trichrome, periodic acid-Schiff and Jones silver stain) using kidney needle core biopsy tissue sections. Based on the evaluation by three renal pathologists, followed by adjudication by a fourth pathologist, we show that the generation of virtual special stains from existing H&E images improves the diagnosis of several non-neoplastic kidney diseases, sampled from 58 unique subjects (P = 0.0095). A second study found that the quality of the computationally generated special stains was statistically equivalent to those which were histochemically stained. This stain-to-stain transformation framework can improve preliminary diagnoses when additional special stains are needed, also providing significant savings in time and cost.
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Tarris G, de Rougemont A, Estienney MA, Journet J, Lariotte AC, Aubignat D, Rebibou JM, De La Vega MF, Legendre M, Belliot G, Martin L. Chronic kidney disease linked to SARS-CoV-2 infection: a case report. BMC Nephrol 2021; 22:278. [PMID: 34376184 PMCID: PMC8353426 DOI: 10.1186/s12882-021-02490-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 08/02/2021] [Indexed: 12/23/2022] Open
Abstract
Background The recent COVID-19 pandemic has raised concerns about patient diagnosis and follow-up of chronically ill patients. Patients suffering from chronic illnesses, concomitantly infected by SARS-CoV-2, globally tend to have a worse prognosis and poor outcomes. Renal tropism and acute kidney injury following SARS-CoV-2 infection has recently been described in the literature, with elevated mortality rates. Furthermore, patients with pre-existing chronic kidney disease, infected by SARS-CoV-2, should be monitored carefully. Here, we report the case of a 69-year-old patient with splenic marginal zone lymphoma, suffering from longstanding chronic kidney disease following SARS-CoV-2 infection. Case presentation A 69-year-old male patient previously diagnosed with pulmonary embolism and splenic marginal zone lymphoma (Splenomegaly, Matutes 2/5, CD5 negative and CD23 positive), was admitted to the hospital with shortness of breath, fever and asthenia. A nasopharyngeal swab test was performed in addition to a CT-scan, which confirmed SARS-CoV-2 infection. Blood creatinine increased following SARS-CoV-2 infection at 130 μmol/l, with usual values at 95 μmol/l. The patient was discharged at home with rest and symptomatic medical treatment (paracetamol and hydration), then readmitted to the hospital in August 2020. A kidney biopsy was therefore conducted as blood creatinine levels were abnormally elevated. Immunodetection performed in a renal biopsy specimen confirmed co-localization of SARS-CoV2 nucleocapsid and protease 3C proteins with ACE2, Lewis x and sialyl-Lewis x antigens in proximal convoluted tubules and podocytes. Co-localization of structural and non-structural viral proteins clearly demonstrated viral replication in proximal convoluted tubules in this chronically ill patient. Additionally, we observed the co-localization of sialyl-Lewis x and ACE2 receptors in the same proximal convoluted tubules. Reverse Transcriptase-Polymerase Chain Reaction test performed on the kidney biopsy was negative, with very low Ct levels (above 40). The patient was finally readmitted to the haematology department for initiation of chemotherapy, including CHOP protocol and Rituximab. Conclusions Our case emphasizes on the importance of monitoring kidney function in immunosuppressed patients and patients suffering from cancer following SARS-CoV-2 infection, through histological screening. Further studies will be required to decipher the mechanisms underlying chronic kidney disease and the putative role of sialyl-Lewis x and HBGA during SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-021-02490-z.
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Affiliation(s)
- Georges Tarris
- Department of Pathology, University Hospital of Dijon, F-21000, Dijon, France. .,National Reference Centre for Gastroenteritis Viruses, Laboratory of Virology, University Hospital of Dijon, F-21000, Dijon, France.
| | - Alexis de Rougemont
- National Reference Centre for Gastroenteritis Viruses, Laboratory of Virology, University Hospital of Dijon, F-21000, Dijon, France
| | - Marie-Anaïs Estienney
- National Reference Centre for Gastroenteritis Viruses, Laboratory of Virology, University Hospital of Dijon, F-21000, Dijon, France
| | - Julien Journet
- Department of Nephrology, William Morey Hospital, F-71100, Chalon-sur-Saône, France
| | | | - Damien Aubignat
- Department of Pathology, University Hospital of Dijon, F-21000, Dijon, France
| | - Jean-Michel Rebibou
- Department of Nephrology, University Hospital of Dijon, F-21000, Dijon, France
| | | | - Mathieu Legendre
- Department of Nephrology, University Hospital of Dijon, F-21000, Dijon, France
| | - Gael Belliot
- National Reference Centre for Gastroenteritis Viruses, Laboratory of Virology, University Hospital of Dijon, F-21000, Dijon, France
| | - Laurent Martin
- Department of Pathology, University Hospital of Dijon, F-21000, Dijon, France
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May RM, Cassol C, Hannoudi A, Larsen CP, Lerma E, Haun RS, Braga JR, Hassen SI, Wilson J, VanBeek C, Vankalakunti M, Barnum L, Walker PD, Bourne TD, Messias NC, Ambruzs JM, Boils CL, Sharma SS, Cossey LN, Baxi PV, Palmer M, Zuckerman J, Walavalkar V, Urisman A, Gallan A, Al-Rabadi LF, Rodby R, Luyckx V, Espino G, Santhana-Krishnan S, Alper B, Lam SG, Hannoudi GN, Matthew D, Belz M, Singer G, Kunaparaju S, Price D, Sauabh C, Rondla C, Abdalla MA, Britton ML, Paul S, Ranjit U, Bichu P, Williamson SR, Sharma Y, Gaspert A, Grosse P, Meyer I, Vasudev B, El Kassem M, Velez JCQ, Caza TN. A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19). Kidney Int 2021; 100:1303-1315. [PMID: 34352311 PMCID: PMC8328528 DOI: 10.1016/j.kint.2021.07.015] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 07/14/2021] [Accepted: 07/23/2021] [Indexed: 12/12/2022]
Abstract
Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19) resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%) which associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19, demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.
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Affiliation(s)
- Rebecca M May
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Clarissa Cassol
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Andrew Hannoudi
- University of Michigan, 500 S State Street, Ann Arbor, MI USA 48109
| | - Christopher P Larsen
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Edgar Lerma
- University of Illinois at Chicago College of Medicine / Advocate Christ Medical Center, Department of Internal Medicine, 1853 W Polk St, Oak Lawn IL USA 60612
| | - Randy S Haun
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Juarez R Braga
- University of Arkansas for Medical Sciences, Nephrology Division, 4301 W Markham St, Little Rock, AR USA 72205
| | - Samar I Hassen
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Jon Wilson
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Christine VanBeek
- AmeriPath Laboratories, Pathology, 225 N.E. 97(th) St #600, Oklahoma City OK USA 73114
| | - Mahesha Vankalakunti
- Manipal Hospital - Bangalore, Department of Pathology, 98 HAL Old Airport Rd, Bangalore, Karnataka India 560017
| | - Lilli Barnum
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Patrick D Walker
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - T David Bourne
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Nidia C Messias
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Josephine M Ambruzs
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Christie L Boils
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Shree S Sharma
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - L Nicholas Cossey
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Pravir V Baxi
- Rush University Medical Center, Nephrology Division, 1620 W. Harrison St, Chicago IL USA 60612
| | - Matthew Palmer
- University of Pennsylvania Perelman School of Medicine, Department of Pathology, 3400 Civic Center Blvd, Philadelphia PA USA 19104
| | - Jonathan Zuckerman
- University of California Los Angeles Health System, Department of Pathology and Laboratory Medicine, 140833 Le Conte Ave, Los Angeles, CA USA 90095
| | - Vighnesh Walavalkar
- UCSF Medical Center, Department of Pathology, 505 Panassus Avenue, CA USA 92103
| | - Anatoly Urisman
- UCSF Medical Center, Department of Pathology, 505 Panassus Avenue, CA USA 92103
| | - Alexander Gallan
- Medical College of Wisconsin, 9200 W. Wisconsin Avenue, WDL Building L73, Milkaukee, WI USA 53226
| | - Laith F Al-Rabadi
- University of Utah School of Medicine, 50 N Medical Drive, Salt Lake City UT 84132
| | - Roger Rodby
- Rush University Medical Center, Nephrology Division, 1620 W. Harrison St, Chicago IL USA 60612
| | - Valerie Luyckx
- University of Zurich, Department of Pathology and Molecular Biology, University Hospital Zurich, Schmelzberstrasse 8091, Zurich, Switzerland; Brigham and Women's Hospital, Renal Division, 75 Francis Street, Boston, MA USA 02115
| | - Gusavo Espino
- Albuquerque Nephrology Associates, 4333 Pan American Fwy NE, Albuquerque, NM USA 87107
| | | | - Brent Alper
- Tulane University School of Medicine, Tulane University Hypertension and Renal Center of Excellence, 6823 St. Charles Avenue, New Orleans, LA USA 70118; Tulane School of Medicine, 1430 Tulane Ave, New Orleans, LA USA 70112
| | - Son G Lam
- Nephrology and Hypertension Associated LTD, 1790 Barron Street, Oxford, MS USA 38655
| | - Ghadeer N Hannoudi
- Michigan Kidney Consultants, 44200 Woodward Ave, Suite 209, Pontiac, MI USA 48341
| | - Dwight Matthew
- Shoals Kidney & Hypertension Center, 422 East Dr Hicks Boulevard, Suite A, Florence, AL USA 35630
| | - Mark Belz
- Iowa Kidney Physicians PC, 1215 Pleasant Street, Suite 100, Des Moines, IA USA 50309
| | - Gary Singer
- Midwest Nephrology Associates, 70 Jungermann Circle, Suite 405, St. Peters, MO USA 63376
| | - Srikanth Kunaparaju
- Richmond Nephrology Associates, 7001 West Broad Street, Suite A, Richmond, VA USA 23294
| | - Deborah Price
- Nephrology Associates of NE Florida, 2 Shircliff Way DePaul Bldg Suite 700, Jacksonville, FL USA 32204
| | - Chawla Sauabh
- Northwest Indiana Nephrology, 6061 Broadway, Merrillville, IN USA 46410
| | - Chetana Rondla
- Georgia Nephrology, 595 Hurricane Shoals Road NW, Suite 100, Lawrenceville, GA USA 30046
| | - Mazen A Abdalla
- The Kidney Clinic, 2386 Clower Street, Suite C105, Snellville, GA USA 30078
| | - Marcus L Britton
- Nephrology & Hypertension Associates LTD, 1542 Medical Park Circle, Tupelo, MS USA 38801
| | - Subir Paul
- Shoals Kidney & Hypertension Center, 422 East Dr Hicks Boulevard, Suite A, Florence, AL USA 35630
| | - Uday Ranjit
- Nephrology Associates of Central Florida, 2501 N Orange Avenue #53, Orlando, FL USA 32804
| | - Prasad Bichu
- Nephrology Associates of Tidewater Ltd., Norfolk, VA USA 23510
| | | | - Yuvraj Sharma
- Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI USA 48202
| | - Ariana Gaspert
- Kantonal Hospital of Graubunden, Loestrasse 170, CH-7000, Chur, Switzerland
| | - Phillipp Grosse
- University of Zurich, Department of Pathology and Molecular Biology, University Hospital Zurich, Schmelzberstrasse 8091, Zurich, Switzerland
| | - Ian Meyer
- Mt Auburn Nephrology, 8260 Pine Road, Cincinnati OH USA 45236
| | - Brahm Vasudev
- Medical College of Wisconsin, 9200 W. Wisconsin Avenue, WDL Building L73, Milkaukee, WI USA 53226
| | - Mohamad El Kassem
- Mohamad El Kassem MD (private practice), Nephrology, Coral Springs, FL USA
| | - Juan Carlos Q Velez
- Ochsner Health System, Deparment of Nephrology, 1514 Jefferson Hwy, New Orleans LA USA 70121; Ochsner Clinical School, The University of Queensland (Australia), Department of Nephrology, St. Lucia, QLD, AUS
| | - Tiffany N Caza
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211.
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Caza TN, Hassen SI, Kuperman M, Sharma SG, Dvanajscak Z, Arthur J, Edmondson R, Storey A, Herzog C, Kenan DJ, Larsen CP. Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis. Kidney Int 2021; 100:171-181. [PMID: 33045259 PMCID: PMC8032825 DOI: 10.1016/j.kint.2020.09.016] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 08/28/2020] [Accepted: 09/03/2020] [Indexed: 12/15/2022]
Abstract
Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. It has been shown in phospholipase A2 receptor positive membranous nephropathy that known antibodies can be detected within sera, determination of the target autoantigen can have diagnostic significance, inform prognosis, and enable non-invasive monitoring of disease activity. Here we utilized mass spectrometry for antigen discovery in laser captured microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue protein G immunoprecipitation studies to interrogate immune complexes from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in some cases of membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1 association was 6.6% of cases of membranous lupus nephritis and in 2.0% of primary membranous nephropathy cases. NCAM1 was found to colocalize with IgG within glomerular immune deposits by confocal microscopy. Additionally, serum from patients with NCAM1-associated membranous nephropathy showed reactivity to NCAM1 recombinant protein on Western blotting and by indirect immunofluorescence assay, demonstrating the presence of circulating antibodies. Thus, we propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.
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Affiliation(s)
| | | | | | | | | | - John Arthur
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Rick Edmondson
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Aaron Storey
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Christian Herzog
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Valente S, Comai G, Malvi D, Corradetti V, La Manna G, Pasquinelli G. Recovering histological sections for ultrastructural diagnosis of glomerular diseases through the pop-off technique. J Nephrol 2021; 34:2085-2092. [PMID: 33929691 DOI: 10.1007/s40620-021-01043-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 03/29/2021] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Electron microscopy (EM) represents an indispensable technique for the diagnosis of kidney glomerular diseases. When dedicated tissue is not available, histological and cryostat sections can be reprocessed for EM using the pop-off technique. Here the practical value of this technique is analysed with emphasis on its accuracy in measuring basement membrane thickness and detecting immune deposits. METHODS Ninety-four histological sections of kidney tissues fixed in Serra's solution, stained with H&E, PAS, and Masson's Trichrome; for EM analysis, the sections were recovered from either treated or untreated microscope slides through the pop-off technique. Some sections were recovered from cryosections allocated for immunofluorescence. RESULTS The ultrastructural details were sufficiently maintained on tissues fixed with Serra's solution despite being considered disadvantageous for EM. The type of microscope slides and the time of biopsy storage did not affect the quality of section recovery. The histological stains had only moderate effects on the electron-density of the glomerular basement membrane (GBM). The pop-off technique reduced the GBM thickness when compared to the conventional EM processing but preserved the electron density of immune deposits. CONCLUSIONS The application of the pop-off method to renal biopsy is a useful recovery method that produces limited but satisfactory results when there is no suitable material for EM. The ultrastructural morphology was retained even from tissues fixed with Serra's solution, and deposits maintained the expected electron density, however, we observed an overall thickness reduction of the GBM that could have a potential impact on thin membrane disease diagnosis.
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Affiliation(s)
- Sabrina Valente
- Biotechnology and Methods in Laboratory Medicine, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
| | - Giorgia Comai
- Nephrology, Dialysis and Kidney Transplantation Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Deborah Malvi
- Pathology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Valeria Corradetti
- Nephrology, Dialysis and Kidney Transplantation Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gaetano La Manna
- Nephrology, Dialysis and Kidney Transplantation Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianandrea Pasquinelli
- Biotechnology and Methods in Laboratory Medicine, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Subcellular Nephro-Vascular Diagnostic Program, Pathology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Kuan K, Schwartz D. Educational Case: Kidney Transplant Rejection. Acad Pathol 2021; 8:23742895211006832. [PMID: 33889718 PMCID: PMC8040549 DOI: 10.1177/23742895211006832] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 12/30/2020] [Accepted: 01/14/2021] [Indexed: 11/17/2022] Open
Abstract
The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.
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Affiliation(s)
- Kevin Kuan
- Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Daniel Schwartz
- Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
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Deceased-Donor Kidney Biopsy Scoring Systems for Predicting Future Graft Function: A Comparative Study. Transplant Proc 2020; 53:906-912. [PMID: 33358418 DOI: 10.1016/j.transproceed.2020.09.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 08/12/2020] [Accepted: 09/06/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Deceased-donor kidney quality pretransplantation is considered critical for future graft function. Assessment of donor kidney quality considers clinical and histologic variables. Several models that incorporate a variety of these factors have been proposed to predict long-term graft survival. METHODS We compared the performance metrics of 4 scoring systems models---the Maryland Aggregate Pathology Index, Banff, Remuzzi, and Leuven---for predicting renal allograft survival. In this retrospective cohort study, we analyzed 173 renal allografts that underwent preoperative baseline biopsy. Donor demographics and donor baseline histopathology data were collected and correlated with graft survival posttransplant. RESULTS Among the 4 scoring systems, none were significantly associated with posttransplant graft survival or early graft function. The Maryland Aggregate Pathology Index scoring system had better predictive capacity in receiver operating characteristic curve analysis; however, the utility as a predictor of graft survival was only slightly better than chance. Baseline histologic features were individually analyzed, and it was found that none were associated with graft survival in this cohort. Among donor demographics, none were significantly associated with graft survival. CONCLUSIONS In our study none of the 4 previously proposed predictive models were associated with graft survival after transplantation. Further studies are needed to define new models with stronger predictive value for graft outcome that could help minimize organ discards.
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Gaber LW, Khan FN, Graviss EA, Nguyen DT, Moore LW, Truong LD, Barrios RJ, Suki WN. Prevalence, Characteristics, and Outcomes of Incidental IgA Glomerular Deposits in Donor Kidneys. Kidney Int Rep 2020; 5:1914-1924. [PMID: 33163712 PMCID: PMC7609995 DOI: 10.1016/j.ekir.2020.08.018] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/13/2020] [Accepted: 08/18/2020] [Indexed: 12/29/2022] Open
Abstract
Introduction Incidental IgA deposits in donor kidneys have unknown sequelae and may predate clinical kidney disease if primed by adverse immunologic or hemodynamic stimuli or may remain dormant. Methods The presence of incidental IgA in post-implantation (T0) biopsies from living (LDK) and deceased donor (DDK) kidneys, and its relationship to post-transplant patient and graft outcomes was investigated in an ethnically diverse US population at a large transplant center. Results Mesangial IgA was present in 20.4% of 802 T0 biopsies; 13.2% and 24.5% of LDK and DDK, respectively. Donors with incidental IgA deposits were more likely to have hypertension and be of Hispanic or Asian origin. Intensity of IgA staining was 1+ (57.3%), 2+ (26.8%), or 3+ (15.8%) of the T0 IgA+ biopsies. Mesangial pathology correlated with higher-intensity IgA staining with less clearance on follow-up (53.8%) versus 79.2% without mesangial pathology. IgA cleared in 91%, 63%, and 40% of follow-up biopsies with 1+, 2+, and 3+ IgA staining, respectively. Early post-transplant rejection and rejection-related graft loss occurred more frequently in IgA+ kidney recipients; however, 5-year kidney function and graft survival were comparable to kidneys without IgA. Conclusion This first and largest report of incidental IgA in T0 biopsies of LDK and DDK in a US ethnically diverse population demonstrated no adverse association between the presence of IgA in donor kidneys and graft or patient survival. Whether IgA in donor kidneys represents latent IgA nephropathy (IgAN) is uncertain; nevertheless, living donors who demonstrate IgA on T0 biopsy deserve careful follow-up.
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Affiliation(s)
- Lillian W. Gaber
- Department of Pathology and Genomic Medicine, Weill Cornell Medical College, Houston Methodist Hospital, Houston, Texas, USA
- Correspondence: Lillian W. Gaber, Houston Methodist Hospital, Department of Pathology and Genomic Medicine, 6565 Fannin Street, Main 227, Houston, Texas 77030, USA.
| | - Faiza N. Khan
- Department of Medicine, Division of Nephrology and Department of Surgery, Transplant Surgery, Baylor Scott and White, Temple, Texas, USA
| | - Edward A. Graviss
- Department of Pathology and Genomic Medicine, Weill Cornell Medical College, Houston Methodist Hospital, Houston, Texas, USA
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, Texas, USA
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | - Duc T. Nguyen
- Department of Pathology and Genomic Medicine, Weill Cornell Medical College, Houston Methodist Hospital, Houston, Texas, USA
| | - Linda W. Moore
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, Texas, USA
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | - Luan D. Truong
- Department of Pathology and Genomic Medicine, Weill Cornell Medical College, Houston Methodist Hospital, Houston, Texas, USA
| | - Roberto J. Barrios
- Department of Pathology and Genomic Medicine, Weill Cornell Medical College, Houston Methodist Hospital, Houston, Texas, USA
| | - Wadi N. Suki
- Department of Medicine, Institute of Academic Medicine, Houston Methodist Hospital, Houston, Texas, USA
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Caza TN, Hassen SI, Dvanajscak Z, Kuperman M, Edmondson R, Herzog C, Storey A, Arthur J, Cossey LN, Sharma SG, Kenan DJ, Larsen CP. NELL1 is a target antigen in malignancy-associated membranous nephropathy. Kidney Int 2020; 99:967-976. [PMID: 32828756 DOI: 10.1016/j.kint.2020.07.039] [Citation(s) in RCA: 116] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 07/02/2020] [Accepted: 07/09/2020] [Indexed: 12/13/2022]
Abstract
Patients with membranous nephropathy have an increased risk of malignancy compared to the general population, but the target antigen for malignancy-associated membranous nephropathy is unknown. To explore this, we utilized mass spectrometry for antigen discovery in malignancy-associated membranous nephropathy examining immune complexes eluted from frozen kidney biopsy tissue using protein G bead immunoglobulin capture. Antigen discovery was performed comparing cases of membranous nephropathy of unknown and known type. Mass spectrophotometric analysis revealed that nerve epidermal growth factor-like 1 (NELL1) immune complexes were uniquely present within the biopsy tissue in membranous nephropathy. Additional NELL1-positive cases were subsequently identified by immunofluorescence. In a consecutive series, 3.8% of PLA2R- and THSD7A-negative cases were NELL1-positive. These NELL1-positive cases had segmental to incomplete IgG capillary loop staining (93.4%) and dominant or co-dominant IgG1-subclass staining (95.5%). The mean age of patients with NELL1-positive membranous nephropathy was 66.8 years, with a slight male predominance (58.2%) and 33% had concurrent malignancy. Compared with PLA2R- and THSD7A-positive cases of membranous nephropathy, there was a greater proportion of cases with malignancies in the NELL1-associated group. Thus, NELL1-associated membranous nephropathy has a unique histopathology characterized by incomplete capillary loop staining, IgG1-predominance, and is more often associated with malignancy than other known types of membranous nephropathy.
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Affiliation(s)
| | | | | | | | - Rick Edmondson
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Christian Herzog
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Aaron Storey
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - John Arthur
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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L'Imperio V, Brambilla V, Cazzaniga G, Ferrario F, Nebuloni M, Pagni F. Digital pathology for the routine diagnosis of renal diseases: a standard model. J Nephrol 2020; 34:681-688. [PMID: 32683656 PMCID: PMC8192318 DOI: 10.1007/s40620-020-00805-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 07/10/2020] [Indexed: 11/03/2022]
Abstract
Whole-slide imaging and virtual microscopy are useful tools implemented in the routine pathology workflow in the last 10 years, allowing primary diagnosis or second-opinions (telepathology) and demonstrating a substantial role in multidisciplinary meetings and education. The regulatory approval of this technology led to the progressive digitalization of routine pathological practice. Previous experiences on renal biopsies stressed the need to create integrate networks to share cases for diagnostic and research purposes. In the current paper, we described a virtual lab studying the routine renal biopsies that have been collected from 14 different Italian Nephrology centers between January 2014 and December 2019. For each case, light microscopy (LM) and immunofluorescence (IF) have been processed, analysed and scanned. Additional pictures (eg. electron micrographs) along with the final encrypted report were uploaded on the web-based platform. The number and type of specimens processed for every technique, the provisional and final diagnosis, and the turnaround-time (TAT) have been recorded. Among 826 cases, 4.5% were second opinion biopsies and only 4% were suboptimal/inadequate for the diagnosis. Transmission electron microscopy (TEM) has been performed on 41% of cases, in 22% changing the final diagnosis, in the remaining 78% contributed to the better definition of the disease. For light microscopy and IF the median TAT was of 2 working days, with only 8.6% with a TAT longer than 5 days. For TEM, the average TAT was 26 days (IQR 6-64). In summary, we systematically reviewed the 6-years long nephropathological experience of an Italian renal pathology service, where digital pathology is a definitive standard of care for the routine diagnosis of glomerulonephritides.
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Affiliation(s)
- Vincenzo L'Imperio
- Department of Medicine and Surgery, Pathology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
| | - Virginia Brambilla
- Department of Medicine and Surgery, Pathology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Giorgio Cazzaniga
- Department of Medicine and Surgery, Pathology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Franco Ferrario
- Department of Medicine and Surgery, Pathology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Manuela Nebuloni
- Pathology Unit, ASST Sacco-Fatebenefratelli, University of Milan, Milan, Italy
| | - Fabio Pagni
- Department of Medicine and Surgery, Pathology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
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A nationwide survey on clinical practice patterns and bleeding complications of percutaneous native kidney biopsy in Japan. Clin Exp Nephrol 2020; 24:389-401. [PMID: 32189101 PMCID: PMC7174253 DOI: 10.1007/s10157-020-01869-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 03/01/2020] [Indexed: 12/29/2022]
Abstract
Background Practice patterns and bleeding complications of percutaneous native kidney biopsy (PNKB) have not recently been investigated and the Japanese Society of Nephrology performed a nationwide questionnaire survey in 2018. Methods The survey consisted of nine sections about PNKB: (1) general indications; (2) indications for high-risk patients; (3) informed consent; (4) pre-biopsy evaluation; (5) procedures; (6) sedation; (7) post-biopsy hemostasis, bed rest, and examinations; (8) bleeding complications; and (9) specimen processing. A supplementary survey examined bleeding requiring transcatheter arterial embolization (TAE). Results Overall, 220 directors of facilities (nephrology facility [NF], 168; pediatric nephrology facility [PF], 52) completed the survey. Indications, procedures, and monitoring protocols varied across facilities. Median lengths of hospital stay were 5 days in NFs and 6 days in PFs. Gauge 14, 16, 18 needles were used in 5%, 56%, 33% in NFs and 0%, 63%, 64% in PFs. Mean limits of needle passes were 5 in NFs and 4 in PFs. The bed rest period was 16–24 h in 60% of NFs and 65% of PFs. Based on 17,342 PNKBs, incidence rates of macroscopic hematuria, erythrocyte transfusion, and TAE were 3.1% (NF, 2.8%; PF, 6.2%), 0.7% (NF, 0.8%; PF, 0%), and 0.2% (NF, 0.2%; PF, 0.06%), respectively. Forty-six percent of facilities processed specimens all for light microscopy, immunofluorescence, and electron microscopy, and 21% processed for light microscopy only. Timing of bleeding requiring TAE varied among PNKB cases. Conclusion Wide variations in practice patterns of PNKB existed among facilities, while PNKBs were performed as safely as previously reported. Electronic supplementary material The online version of this article (10.1007/s10157-020-01869-w) contains supplementary material, which is available to authorized users.
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Royal V, Zee J, Liu Q, Avila-Casado C, Smith AR, Liu G, Mariani LH, Hewitt S, Holzman LB, Gillespie BW, Hodgin JB, Barisoni L. Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes. J Am Soc Nephrol 2020; 31:841-854. [PMID: 32086276 DOI: 10.1681/asn.2019080825] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 12/31/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The analysis and reporting of glomerular features ascertained by electron microscopy are limited to few parameters with minimal predictive value, despite some contributions to disease diagnoses. METHODS We investigated the prognostic value of 12 electron microscopy histologic and ultrastructural changes (descriptors) from the Nephrotic Syndrome Study Network (NEPTUNE) Digital Pathology Scoring System. Study pathologists scored 12 descriptors in NEPTUNE renal biopsies from 242 patients with minimal change disease or FSGS, with duplicate readings to evaluate reproducibility. We performed consensus clustering of patients to identify unique electron microscopy profiles. For both individual descriptors and clusters, we used Cox regression models to assess associations with time from biopsy to proteinuria remission and time to a composite progression outcome (≥40% decline in eGFR, with eGFR<60 ml/min per 1.73 m2, or ESKD), and linear mixed models for longitudinal eGFR measures. RESULTS Intrarater and interrater reproducibility was >0.60 for 12 out of 12 and seven out of 12 descriptors, respectively. Individual podocyte descriptors such as effacement and microvillous transformation were associated with complete remission, whereas endothelial cell and glomerular basement membrane abnormalities were associated with progression. We identified six descriptor-based clusters with distinct electron microscopy profiles and clinical outcomes. Patients in a cluster with more prominent foot process effacement and microvillous transformation had the highest rates of complete proteinuria remission, whereas patients in clusters with extensive loss of primary processes and endothelial cell damage had the highest rates of the composite progression outcome. CONCLUSIONS Systematic analysis of electron microscopic findings reveals clusters of findings associated with either proteinuria remission or disease progression.
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Affiliation(s)
- Virginie Royal
- Department of Pathology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Québec, Canada;
| | - Jarcy Zee
- Arbor Research Collaborative for Health, Ann Arbor, Michigan
| | - Qian Liu
- Arbor Research Collaborative for Health, Ann Arbor, Michigan
| | - Carmen Avila-Casado
- Department of Laboratory Medicine, University of Toronto, Scarborough, Ontario, Canada
| | - Abigail R Smith
- Arbor Research Collaborative for Health, Ann Arbor, Michigan
| | - Gang Liu
- Arbor Research Collaborative for Health, Ann Arbor, Michigan
| | - Laura H Mariani
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Stephen Hewitt
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Lawrence B Holzman
- Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Brenda W Gillespie
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Jeffrey B Hodgin
- Renal Pathology, Department of Pathology, University of Michigan, Ann Arbor, Michigan
| | - Laura Barisoni
- Department of Pathology, Duke University, Durham, North Carolina
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