1. Figure 2 Organ crosstalk in the pathophysiology
of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD)
Figure 2 | Organ crosstalk in the pathophysiology of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Many factors, such as caloric intake, dietary factors (such as high fructose consumption and low vitamin D levels), genetic factors and inflammation of visceral adipose tissue can increase an individual's risk of NAFLD. Increased amounts of non-esterified fatty acids (NEFAs) resulting from the expansion of intra-abdominal visceral adipose tissue are associated with an increase in NF-κB and inflammatory pathways, dysregulation of adipokine production leading to decreased adiponectin levels and impaired insulin signalling. Progression of liver dysfunction triggers pathways that might influence the development of CKD. For example, insulin resistance and atherogenic dyslipidaemia as well as proinflammatory factors, prothrombotic factors and profibrogenic molecules can promote vascular and renal damage. Reduced activation of the energy sensor, 5′-AMP activated protein kinase (AMPK), in response to reduced adiponectin levels further stimulates proinflammatory and profibrogenic mechanisms. Activation of the renin–angiotensin system (RAS) and endothelial cells might also contribute to liver and kidney dysfunction by increasing oxidative stress, inflammation and coagulation pathways. Increased production of uraemic toxins by intestinal microbiota in the setting of CKD might induce further renal, liver and cardiovascular damage through inflammatory, oxidative and fibrotic pathways. Dysbiosis of the intestinal microbiota, which often occurs with obesity, potentially influences NAFLD, CKD, and type 2 diabetes mellitus (T2DM) through complex mechanisms. Finally, cardiovascular disease (CVD), the risk of which is increased in the setting of NAFLD, T2DM or intestinal dysbiosis, can influence the development of renal dysfunction (and vice versa) through cardiorenal interactions. AGE, advanced glycation end-product; NASH, nonalcoholic steatohepatitis; ROS, reactive oxygen species; SCFA, short-chain fatty acid; TMAO, trimethylamine oxide.
Targher, G. & Byrne, C. D. (2017) Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease
Nat. Rev. Nephrol. doi: /nrneph