title: Emerging Liver-Kidney Interactions in Nonalcoholic Fatty Liver Disease.
abstract: Mounting evidence connects non-alcoholic fatty liver disease (NAFLD) to chronic kidney disease (CKD). We review emerging mechanistic links between NAFLD and CKD, including altered activation of angiotensin converting enzyme (ACE)-2, nutrient/energy sensors sirtuin-1 and AMP-activated kinase, as well as impaired antioxidant defense mediated by nuclear factor erythroid 2-related factor-2 (Nrf2). Dietary fructose excess may also contribute to NAFLD and CKD. NAFLD affects renal injury through lipoprotein dysmetabolism and altered secretion of the hepatokines fibroblast growth factor-21, fetuin-A, insulin-like growth factor-1, and syndecan-1. CKD may mutually aggravate NAFLD and associated metabolic disturbances through altered intestinal barrier function and microbiota composition, the accumulation of uremic toxic metabolites, and alterations in pre-receptor glucocorticoid metabolism. We conclude by discussing the implications of these findings for the treatment of NAFLD and CKD.
authors.affiliation: Gradenigo Hospital, University of Turin, Turin, Italy. Electronic address: 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, Royal Melbourne and Western Hospital, Victoria, University of Melbourne, Melbourne, 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: 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: D000818:Animals; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000209:etiology*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000209:etiology*
keywords: CKD; NAFLD; NASH; eGFR; renal function