Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities
| Autor: | Solomon Cohney, Maurizio Cassader, Giovanni Musso, Franco De Michieli, Roberto Gambino, Francesca Saba, Silvia Pinach |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endocrinology Diabetes and Metabolism Peroxisome Proliferator-Activated Receptors Fructose Disease urologic and male genital diseases Bioinformatics Epigenesis Genetic Diabetic nephropathy 03 medical and health sciences Endocrinology 0302 clinical medicine Non-alcoholic Fatty Liver Disease Risk Factors Internal Medicine Advanced and Specialized Nursing Diabetes mellitus Internal medicine Nonalcoholic fatty liver disease medicine Vitamin D and neurology Humans Renal Insufficiency Chronic Vitamin D Randomized Controlled Trials as Topic Inflammation business.industry Fatty liver Lipid Metabolism medicine.disease Fibrosis female genital diseases and pregnancy complications Diet Diabetes and Metabolism Fatty Liver 030104 developmental biology Liver Kidney Failure Chronic 030211 gastroenterology & hepatology Farnesoid X receptor business Kidney disease |
| Zdroj: | Diabetes Care. 39:1830-1845 |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc15-1182 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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