{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:03:11Z","timestamp":1790787791751,"version":"4.1.0"},"reference-count":137,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T00:00:00Z","timestamp":1474502400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:p>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\u2013activated 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\u2013glucose 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.<\/jats:p>","DOI":"10.2337\/dc15-1182","type":"journal-article","created":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T19:37:31Z","timestamp":1474573051000},"page":"1830-1845","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":150,"title":["Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities"],"prefix":"10.2337","volume":"39","author":[{"given":"Giovanni","family":"Musso","sequence":"first","affiliation":[{"name":"Humanitas Gradenigo Hospital, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Cassader","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon","family":"Cohney","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Western & Royal Melbourne Hospitals, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"De Michieli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pinach","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gambino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2016,9,13]]},"reference":[{"key":"2022031123352977700_B1","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1093\/ndt\/gfr547","article-title":"Measuring the population burden of chronic kidney disease: a systematic literature review of the estimated prevalence of impaired kidney function","volume":"27","author":"McCullough","year":"2012","journal-title":"Nephrol Dial Transplant"},{"key":"2022031123352977700_B2","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/S0140-6736(14)62459-4","article-title":"Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis","volume":"385","author":"Palmer","year":"2015","journal-title":"Lancet"},{"key":"2022031123352977700_B3","doi-asserted-by":"crossref","first-page":"e1001680","DOI":"10.1371\/journal.pmed.1001680","article-title":"Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis","volume":"11","author":"Musso","year":"2014","journal-title":"PLoS Med"},{"key":"2022031123352977700_B4"},{"key":"2022031123352977700_B5","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/TP.0000000000000048","article-title":"Evolving frequency and outcomes of simultaneous liver kidney transplants based on liver disease etiology","volume":"98","author":"Singal","year":"2014","journal-title":"Transplantation"},{"key":"2022031123352977700_B6","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1159\/000355808","article-title":"Nonalcoholic fatty liver disease (NAFLD) and cardiovascular risk in renal transplant recipients","volume":"39","author":"Mikolasevic","year":"2014","journal-title":"Kidney Blood Press Res"},{"key":"2022031123352977700_B7","unstructured":"Sugar and Sweeteners Team, Market and Trade Economics, Economic Research Service, US Department of Agriculture. 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