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      Glomerular developmental delay and proteinuria in the preterm neonatal rabbit

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          Abstract

          Recent advances in neonatal care have improved the survival rate of those born premature. But prenatal conditions, premature birth and clinical interventions can lead to transient and permanent problems in these fragile patients. Premature birth (<36 gestational weeks) occurs during critical renal development and maturation. Some consequences have been observed but the exact pathophysiology is still not entirely known. This experimental animal study aims to investigate the effect of premature birth on postnatal nephrogenesis in premature neonatal rabbits compared to term rabbits of the same corrected age. We analyzed renal morphology, glomerular maturity and functional parameters (proteinuria and protein/creatinine ratio) in three cohorts of rabbit pups: preterm (G28), preterm at day 7 of life (G28+7) and term at day 4 of life (G31+4). We found no significant differences in kidney volume and weight, and relative kidney volume between the cohorts. Nephrogenic zone width increased significantly over time when comparing G31 + 4 to G28. The renal corpuscle surface area, in the inner cortex and outer cortex, tended to decrease significantly after birth in both preterm and term groups. With regard to glomerular maturity, we found that the kidneys in the preterm cohorts were still in an immature state (presence of vesicles and capillary loop stage). Importantly, significant differences in proteinuria and protein/creatinine ratio were found. G28 + 7 showed increased proteinuria ( p = 0.019) and an increased protein/creatinine ratio ( p = 0.023) in comparison to G31 +4. In conclusion, these results suggest that the preterm rabbit kidney tends to linger in the immature glomerular stages and shows signs of a reduced renal functionality compared to the kidney born at term, which could in time lead to short- and long-term health consequences.

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          QuPath: Open source software for digital pathology image analysis

          QuPath is new bioimage analysis software designed to meet the growing need for a user-friendly, extensible, open-source solution for digital pathology and whole slide image analysis. In addition to offering a comprehensive panel of tumor identification and high-throughput biomarker evaluation tools, QuPath provides researchers with powerful batch-processing and scripting functionality, and an extensible platform with which to develop and share new algorithms to analyze complex tissue images. Furthermore, QuPath’s flexible design makes it suitable for a wide range of additional image analysis applications across biomedical research.
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            Aminoglycosides: nephrotoxicity.

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              Accelerated maturation and abnormal morphology in the preterm neonatal kidney.

              Nephrogenesis is ongoing at the time of birth for the majority of preterm infants, but whether postnatal renal development follows a similar trajectory to normal in utero growth is unknown. Here, we examined tissue collected at autopsy from 28 kidneys from preterm neonates, whose postnatal survival ranged from 2 to 68 days, including 6 that had restricted intrauterine growth. In addition, we examined kidneys from 32 still-born gestational controls. We assessed the width of the nephrogenic zone, number of glomerular generations, cross-sectional area of the renal corpuscle, and glomerular maturity and morphology. Renal maturation accelerated after preterm birth, with an increased number of glomerular generations and a decreased width of the nephrogenic zone in the kidneys of preterm neonates. Of particular concern, compared with gestational controls, preterm kidneys had a greater percentage of morphologically abnormal glomeruli and a significantly larger cross-sectional area of the renal corpuscle, suggestive of renal hyperfiltration. These observations suggest that the preterm kidney may have fewer functional nephrons, thereby increasing vulnerability to impaired renal function in both the early postnatal period and later in life. Copyright © 2011 by the American Society of Nephrology
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Methodology
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 November 2020
                2020
                : 15
                : 11
                : e0241384
                Affiliations
                [1 ] Faculty of Medicine, Amsterdam UMC, Amsterdam, The Netherlands
                [2 ] Department of Development and Regeneration, KU Leuven, Leuven, Belgium
                [3 ] Department of Paediatrics, Division Woman and Child, University Hospitals Leuven, Leuven, Belgium
                [4 ] Department of Obstetrics and Gynaecology, Division Woman and Child, University Hospitals Leuven, Leuven, Belgium
                [5 ] Institute for Women’s Health, University College London, London, United Kingdom
                Centre Hospitalier Universitaire Vaudois, FRANCE
                Author notes

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

                Author information
                https://orcid.org/0000-0002-4820-143X
                https://orcid.org/0000-0001-9339-5408
                Article
                PONE-D-20-11602
                10.1371/journal.pone.0241384
                7652305
                33166318
                52dd0155-05d2-454b-83af-e61a4cb88c35
                © 2020 de Winter 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
                : 21 May 2020
                : 14 October 2020
                Page count
                Figures: 4, Tables: 1, Pages: 12
                Funding
                AG is funded with support of the Erasmus+ Programme of the European Union (Framework Agreement number: 2013-0040). JD is funded by The Research Foundation – Flanders (FWO Flanders) as clinical researcher (1.801207). EL is funded by The Research Foundation – Flanders (FWO Flanders) as clinical investigator (1801110N). This study was supported by The Research Foundation – Flanders (FWO Flanders) (grant G0C4419N) and Katholieke Universiteit Leuven (C2 grant: C24/18/101). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Leporids
                Rabbits
                Biology and Life Sciences
                Zoology
                Animals
                Vertebrates
                Amniotes
                Mammals
                Leporids
                Rabbits
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Animal Models
                Rabbits
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Birth
                Preterm Birth
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Birth
                Preterm Birth
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Pregnancy Complications
                Preterm Birth
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Pregnancy Complications
                Preterm Birth
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Glomeruli
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Glomeruli
                Biology and Life Sciences
                Developmental Biology
                Neonates
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Proteinuria
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Vesicles
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Creatinine
                Custom metadata
                All raw data is available from the Zenodo database (DOI: 10.5281/zenodo.3760389).

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