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Expert Opin Ther Targets. 2019 Jun;23(6):495-509. doi: 10.1080/14728222.2019.1609451. Epub 2019 May 3.

Emerging therapeutic strategies for transplantation-induced acute kidney injury: protecting the organelles and the vascular bed.

Author information

1
a Laboratory of Cellular and Molecular Biology , Center for Cancer Research, National Cancer Institute , Bethesda , MD , USA.
2
b IRTOMIT , Inserm U1082 , Poitiers , France.
3
c Faculté de Médecine et de Pharmacie , Université de Poitiers , Poitiers , France.
4
d CHU Poitiers , Service de Biochimie , Poitiers , France.
5
e Fédération Hospitalo-Universitaire SUPORT , Poitiers , France.
6
f Faculté de Médecine , Université Claude Bernard Lyon 1 , Villeurbanne , France.
7
g Hospices Civiles de Lyon , Service d'urologie et de chirurgie de la transplantation , Lyon , France.
8
h CHU de Poitiers , Service de chirurgie générale et endocrinienne , Poitiers , France.
9
i Faculté de Médecine et de Pharmacie , ABS Lab (Laboratoire d'Anatomie, Biomécanique et Simulation), Université de Poitiers , Poitiers , France.
10
j Laboratorio de Fisiología Cardiovascular y Trasplante Renal, Unidad de Medicina Traslacional , Instituto de Investigaciones Biomédicas, UNAM and Instituto Nacional de Cardiología Ignacio Chávez , Mexico City , Mexico.
11
k INSERM, UMRS 1138, Team 1 , Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris, Descartes University , Paris , France.
12
l LP2M CNRS-UMR7370, LabEx ICST , Medical Faculty, Université Côte d'Azur , Nice , France.
13
m IBiSA Plateforme 'plate-forme MOdélisation Préclinique - Innovation Chirurgicale et Technologique (MOPICT)', Domaine Expérimental du Magneraud , Surgères , France.

Abstract

Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians in a broad variety of clinical settings such as perioperative and intensive care. Renal IRI induced acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs. Areas covered: This paper focuses on the pathophysiology of transplantation-related AKI and recent findings on cellular stress responses at the intersection of 1. The Unfolded protein response; 2. Mitochondrial dysfunction; 3. The benefits of mineralocorticoid receptor antagonists. Lastly, perspectives are offered to the readers. Expert opinion: Renal IRI is caused by a sudden and temporary impairment of blood flow to the organ. Defining the underlying cellular cascades involved in IRI will assist us in the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer several advantages compared to targeting downstream inflammatory and fibrosis processes. An improved understanding of the cellular pathophysiological mechanisms leading to kidney injury will hopefully offer improved targeted therapies to prevent and treat the injury in the future.

KEYWORDS:

Transplantation-induced acute kidney injury; delayed graft function; gene therapy; ischemia reperfusion; mineralocorticoid receptor; mitochondrial energetic modulation; stem cells; unfolded protein response

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