Anna Zuk1, Joseph V Bonventre2,3,4. 1. Research and Development, Akebia Therapeutics, Inc, Cambridge. 2. Department of Medicine, Harvard Medical School. 3. Renal Division, Brigham and Women's Hospital, Boston. 4. Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: Acute kidney injury (AKI) remains a major unmet medical need and associates with high morbidity, mortality, and healthcare costs. Among survivors, long-term outcomes of AKI can include development of chronic kidney disease (CKD) or progression of preexisting CKD. In this review, we focus on ongoing efforts by the AKI community to understand the human AKI to CKD continuum, with an emphasis on the cellular stress responses that underlie AKI and the maladaptive responses that persist in the acute-to-chronic phase. The emphasis is on work that has been published in the past year in this rapidly expanding field. RECENT FINDINGS: Recent studies in preclinical models highlight the importance of mitochondrial dysfunction, cell death, and inflammation on the underlying pathogenesis of AKI. These pathogenic mechanisms can resolve with adaptive kidney repair but persist in maladaptive repair that leads to progressive chronic disease. The complexity and interconnections of these pathways involve cross-talk between the tubular epithelium, endothelium, and interstitial compartments. SUMMARY: Approaches which lessen or counteract these cellular responses represent novel strategies to prevent AKI and stop or slow down the progression to CKD.
PURPOSE OF REVIEW: Acute kidney injury (AKI) remains a major unmet medical need and associates with high morbidity, mortality, and healthcare costs. Among survivors, long-term outcomes of AKI can include development of chronic kidney disease (CKD) or progression of preexisting CKD. In this review, we focus on ongoing efforts by the AKI community to understand the human AKI to CKD continuum, with an emphasis on the cellular stress responses that underlie AKI and the maladaptive responses that persist in the acute-to-chronic phase. The emphasis is on work that has been published in the past year in this rapidly expanding field. RECENT FINDINGS: Recent studies in preclinical models highlight the importance of mitochondrial dysfunction, cell death, and inflammation on the underlying pathogenesis of AKI. These pathogenic mechanisms can resolve with adaptive kidney repair but persist in maladaptive repair that leads to progressive chronic disease. The complexity and interconnections of these pathways involve cross-talk between the tubular epithelium, endothelium, and interstitial compartments. SUMMARY: Approaches which lessen or counteract these cellular responses represent novel strategies to prevent AKI and stop or slow down the progression to CKD.
Authors: Benjamin D Humphreys; M Todd Valerius; Akio Kobayashi; Joshua W Mugford; Savuth Soeung; Jeremy S Duffield; Andrew P McMahon; Joseph V Bonventre Journal: Cell Stem Cell Date: 2008-03-06 Impact factor: 24.633
Authors: Mark Lipphardt; Jong W Song; Kei Matsumoto; Sina Dadafarin; Hassan Dihazi; Gerhard Müller; Michael S Goligorsky Journal: Kidney Int Date: 2017-05-03 Impact factor: 10.612
Authors: Juanjuan Zhao; Katherine Lupino; Benjamin J Wilkins; Chengxiang Qiu; Jian Liu; Yasuhiro Omura; Amanda L Allred; Caitlin McDonald; Katalin Susztak; Grant D Barish; Liming Pei Journal: Proc Natl Acad Sci U S A Date: 2018-05-07 Impact factor: 11.205
Authors: Omar H Maarouf; Mayuko Uehara; Vivek Kasinath; Zhabiz Solhjou; Naima Banouni; Baharak Bahmani; Liwei Jiang; Osman A Yilmam; Indira Guleria; Scott B Lovitch; Jane L Grogan; Paolo Fiorina; Peter T Sage; Jonathan S Bromberg; Martina M McGrath; Reza Abdi Journal: JCI Insight Date: 2018-07-12
Authors: Maria B Monteiro; Susanne Ramm; Vidya Chandrasekaran; Sarah A Boswell; Elijah J Weber; Kevin A Lidberg; Edward J Kelly; Vishal S Vaidya Journal: J Am Soc Nephrol Date: 2018-10-25 Impact factor: 10.121
Authors: Maria Agustina Battistone; Alexandra C Mendelsohn; Raul German Spallanzani; Andrew S Allegretti; Rachel N Liberman; Juliana Sesma; Sahir Kalim; Susan M Wall; Joseph V Bonventre; Eduardo R Lazarowski; Dennis Brown; Sylvie Breton Journal: J Clin Invest Date: 2020-07-01 Impact factor: 14.808
Authors: Joāo S Periquito; Thomas Gladytz; Jason M Millward; Paula Ramos Delgado; Kathleen Cantow; Dirk Grosenick; Luis Hummel; Ariane Anger; Kaixuan Zhao; Erdmann Seeliger; Andreas Pohlmann; Sonia Waiczies; Thoralf Niendorf Journal: Quant Imaging Med Surg Date: 2021-07
Authors: Ian Vargas; Daniel J Stephenson; Margaret Baldwin; Joseph P Gaut; Charles E Chalfant; Hua Pan; Samuel A Wickline Journal: Nanomedicine Date: 2021-07-23 Impact factor: 5.307