Morel, Jean -DavidSleiman, Maroun BouLi, Terytty Yangvon Alvensleben, GiacomoBachmann, Alexis M.Hofer, DinaBroeckx, EllenMa, Jing YingCarreira, ViniciusChen, TaoAzhar, NabilGonzalez-Villalobos, Romer A.Breyer, MatthewReilly, DermotMullican, ShannonAuwerx, Johan2023-04-242023-04-242023-04-242023-02-0810.1172/jci.insight.164626https://infoscience.epfl.ch/handle/20.500.14299/197108WOS:000963808000001Acute kidney failure and chronic kidney disease are global health issues steadily rising in incidence and prevalence. Animal models on a single genetic background have so far failed to recapitulate the clinical presentation of human nephropathies. Here, we used a simple model of folic acid-induced kidney injury in 7 highly diverse mouse strains. We measured plasma and urine parameters, as well as renal histopathology and mRNA expression data, at 1, 2, and 6 weeks after injury, covering the early recovery and long-term remission. We observed an extensive strain-specific response ranging from complete resistance of the CAST/EiJ to high sensitivity of the C57BL/6J, DBA/2J, and PWK/PhJ strains. In susceptible strains, the severe early kidney injury was accompanied by the induction of mitochondrial stress response (MSR) genes and the attenuation of NAD+ synthesis pathways. This is associated with delayed healing and a prolonged inflammatory and adaptive immune response 6 weeks after insult, heralding a transition to chronic kidney disease. Through a thorough comparison of the transcriptomic response in mouse and human disease, we show that critical metabolic gene alterations were shared across species, and we highlight the PWK/PhJ strain as an emergent model of transition from acute kidney injury to chronic disease.Medicine, Research & ExperimentalResearch & Experimental Medicinediseasemodelsbiogenesismitophagyrisktext::journal::journal article::research article