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      Oxalate deposition in renal allograft biopsies within 3 months after transplantation is associated with allograft dysfunction

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          Abstract

          Background

          Calcium oxalate (CaOx) deposition in the kidney may lead to loss of native renal function but little is known about the prevalence and role of CaOx deposition in transplanted kidneys.

          Methods

          In patients transplanted in 2014 and 2015, all for-cause renal allograft biopsies obtained within 3 months post-transplantation were retrospectively investigated for CaOx deposition. Additionally, all preimplantation renal biopsies obtained in 2000 and 2001 were studied.

          Results

          In 2014 and 2015, 388 patients were transplanted, of whom 149 had at least one for-cause renal biopsy. Twenty-six (17%) patients had CaOx deposition. In the population with CaOx deposition: Patients had significantly more often been treated with dialysis before transplantation (89 vs. 64%; p = 0.011); delayed graft function occurred more frequently (42 vs. 23%; p = 0.038); and the eGFR at the time of first biopsy was significantly worse (21 vs. 29 ml/min/1.73m 2; p = 0.037). In a multivariate logistic regression analysis, eGFR at the time of first biopsy (OR 0.958, 95%-Cl: 0.924–0.993, p = 0.019), dialysis before transplantation (OR 4.868, 95%-Cl: 1.128–21.003, p = 0.034) and the time of first biopsy after transplantation (OR 1.037, 95%-Cl: 1.013–1.062, p = 0.002) were independently associated with CaOx deposition. Graft survival censored for death was significantly worse in patients with CaOx deposition (p = 0.018). In only 1 of 106 preimplantation biopsies CaOx deposition was found (0.94%).

          Conclusion

          CaOx deposition appears to be primarily recipient-derived and is frequently observed in for-cause renal allograft biopsies obtained within 3 months post-transplantation. It is associated with inferior renal function at the time of biopsy and worse graft survival.

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          Most cited references31

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          ImageJ for microscopy.

          ImageJ is an essential tool for us that fulfills most of our routine image processing and analysis requirements. The near-comprehensive range of import filters that allow easy access to image and meta-data, a broad suite processing and analysis routine, and enthusiastic support from a friendly mailing list are invaluable for all microscopy labs and facilities-not just those on a budget.
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            Marked variation in the definition and diagnosis of delayed graft function: a systematic review.

            The term delayed graft function (DGF) is commonly used to describe the need for dialysis after receiving a kidney transplant. DGF increases morbidity after transplantation, prolongs hospitalization and may lead to premature graft failure. Various definitions of DGF are used in the literature without a uniformly accepted technique to identify DGF. We performed a systematic review of the literature to identify all of the different definitions and diagnostic techniques to identify DGF. We identified 18 unique definitions for DGF and 10 diagnostic techniques to identify DGF. The utilization of heterogeneous clinical criteria to define DGF has certain limitations. It will lead to delayed and sometimes inaccurate diagnosis of DGF. Hence a diagnostic test that identifies DGF reliably and early is necessary. Heterogeneity, in the definitions used for DGF, hinders the evolution of a diagnostic technique to identify DGF, which requires a gold standard definition. We are in need of a new definition that is uniformly accepted across the kidney transplant community. The new definition will be helpful in promoting better communication among transplant professionals and aids in comparing clinical studies of diagnostic techniques to identify DGF and thus may facilitate clinical trials of interventions for the treatment of DGF.
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              Mechanism of calcium oxalate renal stone formation and renal tubular cell injury.

              Formation of calcium oxalate stones tends to increase with age and begins from the attachment of a crystal formed in the cavity of renal tubules to the surface of renal tubular epithelial cells. Though most of the crystals formed in the cavity of renal tubules are discharged as is in the urine, in healthy people, crystals that attach to the surface of renal tubular epithelial cells are thought to be digested by macrophages and/or lysosomes inside of cells. However, in individuals with hyperoxaluria or crystal urine, renal tubular cells are injured and crystals easily become attached to them. Various factors are thought to be involved in renal tubular cell injury. Crystals attached to the surface of renal tubular cells are taken into the cells (crystal-cell interaction). And then the crystal and crystal aggregates grow, and finally a stone is formed.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: Writing – original draft
                Role: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 April 2019
                2019
                : 14
                : 4
                : e0214940
                Affiliations
                [1 ] Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [2 ] Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [3 ] Department of Internal Medicine, Division of Nephrology and Transplantation, University Medical Center Rotterdam, Rotterdam, The Netherlands
                University of Toledo, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-6295-2291
                Article
                PONE-D-18-29441
                10.1371/journal.pone.0214940
                6467373
                30990835
                d44cedc7-9e81-49b7-b5aa-a6a81ea3c392
                © 2019 Snijders et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 November 2018
                : 22 March 2019
                Page count
                Figures: 3, Tables: 1, Pages: 12
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biopsy
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Renal Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Urinary System Procedures
                Renal Transplantation
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Dicarboxylic Acids
                Oxalic Acid
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Earth Sciences
                Atmospheric Science
                Atmospheric Chemistry
                Acid Deposition
                Physical Sciences
                Chemistry
                Environmental Chemistry
                Atmospheric Chemistry
                Acid Deposition
                Ecology and Environmental Sciences
                Environmental Chemistry
                Atmospheric Chemistry
                Acid Deposition
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Transplantation Immunology
                Transplant Rejection
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Transplantation Immunology
                Transplant Rejection
                Medicine and Health Sciences
                Immunology
                Clinical Immunology
                Transplantation Immunology
                Transplant Rejection
                Biology and Life Sciences
                Anatomy
                Renal System
                Medicine and Health Sciences
                Anatomy
                Renal System
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

                Uncategorized
                Uncategorized

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