Sandra Rayego-Mateos, José Luis Morgado-Pascual, Javier Egea, Sebastian Mas, José M. Villalba, Alfonso Rubio-Navarro, Lucas Opazo-Ríos, Alejandra Palomino-Antolín, Jesús Egido, Cristina García-Caballero, Melania Guerrero-Hue, Alberto Ortiz, Juan Antonio Moreno, Carmen Herencia, Cristina Vázquez-Carballo, UAM. Departamento de Medicina, [Guerrero-Hue,M, Rayego-Mateos,S, García-Caballero,C, Morgado-Pascual,JL, Moreno,JA] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Cordoba, Spain. [Vázquez-Carballo,C, Opazo-Rios,L, Herencia,C, Mas,S, Ortiz,A, Egido,J] Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain. [Palomino-Antolín,A, Egea,J] Research Unit, Hospital Universitario Santa Cristina, IIS-Hospital Universitario de la Princesa, Madrid, Spain. [Palomino-Antolín,A, Egea,J] Departament of Pharmacology and Therapeutics, Medicine Faculty, Instituto Teófilo Hernando, Autónoma University, Madrid, Spain. [Opazo-Rios,L, Egido,J] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. [Ortiz,A] Red Nacional Investigaciones Nefrológicas (REDINREN), Madrid, Spain. [Rubio-Navarro,A] Weill Center for Metabolic Health and Division of Cardiology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA. [Villalba,JM, Moreno,JA] Department of Cell Biology, Physiology, and Immunology, Agrifood Campus of International Excellence (ceiA3), University of Cordoba, Cordoba, Spain. [Moreno,JA] Hospital Universitario Reina Sofia, Cordoba, Spain. [Moreno,JA] Biomedical Research Networking Center on Cardiovascular Diseases (CIBERCV), Madrid, Spain., and The authors’ work has been supported by grants FIS/Fondos FEDER (PI17/00130, PI17/00257, PI17/01495, PI18/01386, PI19/00815, PI20/00375, PI20/00487 ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) and Cardiovascular (CIBERCV), Spanish Ministry of Science and Innovation (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369, FJC2019-042028), The 'PFIS'and 'Sara Borrell' training program of the ISCIII supported the salary of MGH (FI18/00310), SR-M (CD19/00021), and CH-B (CP16/00017). Spanish Ministerio de Ciencia, Innovación y Universidades (MICIU) grant RTI2018-100695-B-I00, Junta de Andalucía grants P18-RT-4264, 1263735-R and BIO-276, the FEDER Funding Program from the European Union, and Universidad de Córdoba (to J.M.V.). No other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Chronic kidney disease (CKD) is one of the fastest-growing causes of death and is predicted to become by 2040 the fifth global cause of death. CKD is characterized by increased oxidative stress and chronic inflammation. However, therapies to slow or prevent CKD progression remain an unmet need. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that plays a key role in protection against oxidative stress and regulation of the inflammatory response. Consequently, the use of compounds targeting Nrf2 has generated growing interest for nephrologists. Pre-clinical and clinical studies have demonstrated that Nrf2-inducing strategies prevent CKD progression and protect from acute kidney injury (AKI). In this article, we review current knowledge on the protective mechanisms mediated by Nrf2 against kidney injury, novel therapeutic strategies to induce Nrf2 activation, and the status of ongoing clinical trials targeting Nrf2 in renal diseases, The authors’work has been supported by grants FIS/Fondos FEDER (PI17/00130, PI17/00257, PI17/01495, PI18/01386, PI19/00815, PI20/00375, PI20/00487 ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) and Cardiovascular (CIBERCV), Spanish Ministry of Science and Innovation (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369, FJC2019-042028), The “PFIS” and “Sara Borrell” training program of the ISCIII supported the salary of MGH (FI18/00310), SR-M (CD19/00021), and CH-B (CP16/00017). Spanish Ministerio de Ciencia, Innovación y Universidades (MICIU) grant RTI2018-100695-B-I00, Junta de Andalucía grants P18-RT-4264, 1263735-R and BIO-276, the FEDER Funding Program from the European Union, and Universidad de Córdoba (to J.M.V.)