Blog
About

1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Prenatal hypoxia increases susceptibility to kidney injury

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Prenatal hypoxia is a gestational stressor that can result in developmental abnormalities or physiological reprogramming, and often decreases cellular capacity against secondary stress. When a developing fetus is exposed to hypoxia, blood flow is preferentially redirected to vital organs including the brain and heart over other organs including the kidney. Hypoxia-induced injury can lead to structural malformations in the kidney; however, even in the absence of structural lesions, hypoxia can physiologically reprogram the kidney leading to decreased function or increased susceptibility to injury. Our investigation in mice reveals that while prenatal hypoxia does not affect normal development of the kidneys, it primes the kidneys to have an increased susceptibility to kidney injury later in life. We found that our model does not develop structural abnormalities when prenatally exposed to modest 12% O 2 as evident by normal histological characterization and gene expression analysis. Further, adult renal structure and function is comparable to mice exposed to ambient oxygen throughout nephrogenesis. However, after induction of kidney injury with a nephrotoxin (cisplatin), the offspring of mice housed in hypoxia exhibit significantly reduced renal function and proximal tubule damage following injury. We conclude that exposure to prenatal hypoxia in utero physiologically reprograms the kidneys leading to increased susceptibility to injury later in life.

          Related collections

          Most cited references 41

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Mechanisms of Cisplatin Nephrotoxicity

          Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. One of the limiting side effects of cisplatin use is nephrotoxicity. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatin-induced renal cell death. It has also become apparent that inflammation provoked by injury to renal epithelial cells serves to amplify kidney injury and dysfunction in vivo. This review summarizes recent advances in our understanding of cisplatin nephrotoxicity and discusses how these advances might lead to more effective prevention.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pathophysiology of acute kidney injury.

            Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia, or nephrotoxicity. An underlying feature is a rapid decline in glomerular filtration rate (GFR) usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or chronic kidney disease (CKD) patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. © 2012 American Physiological Society. Compr Physiol 2:1303-1353, 2012.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mammalian kidney development: principles, progress, and projections.

              The mammalian kidney is a vital organ with considerable cellular complexity and functional diversity. Kidney development is notable for requiring distinct but coincident tubulogenic processes involving reciprocal inductive signals between mesenchymal and epithelial progenitor compartments. Key molecular pathways mediating these interactions have been identified. Further, advances in the analysis of gene expression and gene activity, coupled with a detailed knowledge of cell origins, are enhancing our understanding of kidney morphogenesis and unraveling the normal processes of postnatal repair and identifying disease-causing mechanisms. This article focuses on recent insights into central regulatory processes governing organ assembly and renal disease, and predicts future directions for the field.
                Bookmark

                Author and article information

                Contributors
                Role: InvestigationRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Investigation
                Role: Data curationRole: Methodology
                Role: Methodology
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 February 2020
                2020
                : 15
                : 2
                Affiliations
                Department of Pediatrics, Division of Nephrology, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
                National Institutes of Health, UNITED STATES
                Author notes

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

                Article
                PONE-D-19-28255
                10.1371/journal.pone.0229618
                7034911
                32084244
                © 2020 Cargill 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.

                Page count
                Figures: 6, Tables: 0, Pages: 16
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
                Award ID: DK096996
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
                Award ID: DK110503
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
                Award ID: DK116370
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000968, American Heart Association;
                Award ID: 17POST33670685
                Award Recipient :
                Dr. Cargill (KRC) was supported by the National Institutes of Health NIDDK (DK116370) and by the UPMC Children’s Hospital of Pittsburgh Research Advisory Committee. Dr. Chiba (TC) was supported by the American Heart Association (17POST33670685) and the Richard King Mellon Institute for Pediatric Research. Dr. Sims-Lucas (SSL) was supported by the National Institutes of Health NIDDK K01 (DK096996) and R03 (DK110503). 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
                Cell Biology
                Hypoxia
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Nephrons
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Nephrons
                Research and Analysis Methods
                Specimen Preparation and Treatment
                Staining
                Immunofluorescence Staining
                Physical Sciences
                Chemistry
                Chemical Elements
                Oxygen
                Medicine and Health Sciences
                Pulmonology
                Medical Hypoxia
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Animal Models
                Mouse Models
                Biology and Life Sciences
                Genetics
                Gene Expression
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

                Uncategorized

                Comments

                Comment on this article