title: Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities.
abstract: Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferator-activated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium-glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium.
authors.affiliation: Humanitas Gradenigo Hospital, University of Turin, Turin, Italy giovanni_musso@yahoo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Musso
authors.affiliation: Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cassader
authors.affiliation: Department of Nephrology, Western & Royal Melbourne Hospitals, Melbourne, VIC, Australia.
authors.forename: Solomon
authors.initials: S
authors.lastname: Cohney
authors.affiliation: Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: De Michieli
authors.affiliation: Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pinach
authors.affiliation: Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Saba
authors.affiliation: Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambino
mesh_terms: D004032:Diet; D044127:Epigenesis, Genetic; D005234:Fatty Liver / Q000150:complications / Q000453:epidemiology*; D005355:Fibrosis; D005632:Fructose / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation; D007676:Kidney Failure, Chronic / Q000150:complications / Q000453:epidemiology*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000453:epidemiology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000453:epidemiology*; D012307:Risk Factors; D014807:Vitamin D / Q000008:administration & dosage
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D014807:Vitamin D; D005632:Fructose