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      Ex vivo confocal microscopy detects basic patterns of acute and chronic lesions using fresh kidney samples

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          ABSTRACT

          Background

          Ex vivo confocal microscopy is a real-time technique that provides high-resolution images of fresh, non-fixed tissues, with an optical resolution comparable to conventional pathology. The objective of this study was to investigate the feasibility of using ex vivo confocal microscopy in fusion mode (FuCM) and the haematoxylin and eosin (H&E)-like digital staining that results for the analysis of basic patterns of lesion in nephropathology.

          Methods

          Forty-eight renal samples were scanned in a fourth-generation ex vivo confocal microscopy device. Samples were subjected to confocal microscopy imaging and were then processed using conventional pathology techniques. Concordance between the techniques was evaluated by means of the percentage of agreement and the κ index.

          Results

          Agreement between conventional microscopy and H&E-like digital staining was strong (κ = 0.88) in the evaluation of acute tubular damage and was substantial (κ = 0.79) in the evaluation of interstitial fibrosis, interstitial inflammation, arterial and arteriolar lesions. H&E-like digital staining also allows rapid identification of extracapillary proliferation (κ = 0.88), necrosis and segmental sclerosis (κ = .88) in the glomerular compartment, but the results reported here are limited because of the small number of cases with these glomerular findings.

          Conclusions

          FuCM proved to be as effective as conventional techniques in evaluating the presence of acute tubular necrosis and interstitial fibrosis changes, but in fresh tissue. The ease of acquisition of ex vivo confocal microscopy images suggests that FuCM may be useful for rapid evaluation of kidney biopsies and to restructure the clinical workflow in renal histopathology.

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          Most cited references26

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          The kappa statistic in reliability studies: use, interpretation, and sample size requirements.

          This article examines and illustrates the use and interpretation of the kappa statistic in musculoskeletal research. The reliability of clinicians' ratings is an important consideration in areas such as diagnosis and the interpretation of examination findings. Often, these ratings lie on a nominal or an ordinal scale. For such data, the kappa coefficient is an appropriate measure of reliability. Kappa is defined, in both weighted and unweighted forms, and its use is illustrated with examples from musculoskeletal research. Factors that can influence the magnitude of kappa (prevalence, bias, and non-independent ratings) are discussed, and ways of evaluating the magnitude of an obtained kappa are considered. The issue of statistical testing of kappa is considered, including the use of confidence intervals, and appropriate sample sizes for reliability studies using kappa are tabulated. The article concludes with recommendations for the use and interpretation of kappa.
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            Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases

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              Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome.

              Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Contributors
                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                June 2023
                27 January 2023
                27 January 2023
                : 16
                : 6
                : 1005-1013
                Affiliations
                Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona , Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Fundación Hospital Clinic , Barcelona, Spain
                Fundación Hospital Clinic , Barcelona, Spain
                Department of Dermatology, Melanoma Unit, Hospital Clínic de Barcelona , Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain
                Department of Dermatology, Melanoma Unit, Hospital Clínic de Barcelona , Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain
                Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona , Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Department of Autoimmune Diseases , Reference Centre for Systemic Autoimmune Diseases of the Spanish Health System, Hospital Clínic de Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Pathology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Reference Centre for Complex Glomerular Diseases of the Spanish Health System, Hospital Clínic de Barcelona , Barcelona,Spain
                Pathology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Reference Centre for Complex Glomerular Diseases of the Spanish Health System, Hospital Clínic de Barcelona , Barcelona,Spain
                Department of Dermatology, Melanoma Unit, Hospital Clínic de Barcelona , Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain
                Department of Autoimmune Diseases , Reference Centre for Systemic Autoimmune Diseases of the Spanish Health System, Hospital Clínic de Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Reference Centre for Complex Glomerular Diseases of the Spanish Health System, Hospital Clínic de Barcelona , Barcelona,Spain
                Pathology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona , Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Reference Centre for Complex Glomerular Diseases of the Spanish Health System, Hospital Clínic de Barcelona , Barcelona,Spain
                Pathology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer , Universitat de Barcelona, Barcelona, Spain
                Reference Centre for Complex Glomerular Diseases of the Spanish Health System, Hospital Clínic de Barcelona , Barcelona,Spain
                Author notes
                Correspondence to: Adriana García-Herrera; E-mail: apgarcia@ 123456clinic.cat
                Correspondence to: Luis F. Quintana; E-mail: lfquinta@ 123456clinic.cat
                Author information
                https://orcid.org/0000-0001-7582-8476
                Article
                sfad019
                10.1093/ckj/sfad019
                10229294
                37260998
                eed9faaf-f83c-4ecc-837c-1cc2a0d36136
                © The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 25 August 2022
                : 26 April 2023
                Page count
                Pages: 9
                Funding
                Funded by: Fondo Europeo de Desarrollo Regional, DOI 10.13039/501100008530;
                Award ID: PI17/00080
                Categories
                Original Article
                AcademicSubjects/MED00340

                Nephrology
                ex vivo confocal microscopy,fluorescence confocal microscopy,fusion confocal microscopy,reflectance confocal microscopy,renal biopsy

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