Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease

Key Points

  • Accumulating evidence indicates that the presence and severity of non-alcoholic fatty liver disease (NAFLD) is strongly associated with an increased prevalence of chronic kidney disease (CKD)

  • The presence and severity of NAFLD predicts the development of incident CKD, independent of traditional cardiorenal risk factors

  • Evidence suggests that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia, and causes the release of proinflammatory, procoagulant, pro-oxidant and profibrogenic mediators that are important in the pathophysiology of CKD

  • Despite the growing evidence linking NAFLD to CKD, whether a causal association exists has not been definitively established

  • These findings call for a more active and systematic search for NAFLD in patients with CKD with a view to potential earlier treatment

Abstract

Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.

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Figure 1: Proposed algorithm for the management of suspected non-alcoholic fatty liver disease (NAFLD) in high-risk individuals.
Figure 2: Organ crosstalk in the pathophysiology of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD).
Figure 3: Potential mechanisms by which intestinal dysbiosis might promote the development of non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD).
Figure 4: Management and therapeutic strategies for non-alcoholic fatty liver disease (NAFLD).

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Acknowledgements

G.T. is supported in part by grants from the University School of Medicine of Verona, Verona, Italy. C.D.B. is supported in part by the Southampton National Institute for Health Research Biomedical Research Centre.

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Both authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

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Correspondence to Giovanni Targher.

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Putative effects of changes in molecules and/or pathways relevant to the pathogenesis of NAFLD and CKD (PDF 253 kb)

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Glossary

Hepatorenal syndrome

A particular and common type of kidney failure that affects patients with cirrhosis or, occasionally, with fulminant liver failure, who have portal hypertension and ascites. This syndrome involves constriction of the blood vessels in the kidneys and dilation of blood vessels in the splanchnic circulation, which supplies the intestines.

Prothrombin time

Prothrombin time, along with its derived measures of prothrombin ratio and international normalized ratio, are assays to evaluate the extrinsic pathway of coagulation. Prothrombin time is the primary assay used to monitor oral anticoagulant therapy.

L cells

L cells are enteric endocrine cells that secrete peptides that are capable of stimulating insulin secretion and modulating satiety.

Cholestasis

A decrease in bile flow owing to impaired secretion by hepatocytes or to obstruction of bile flow through intrahepatic or extrahepatic bile ducts.

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Targher, G., Byrne, C. Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease. Nat Rev Nephrol 13, 297–310 (2017). https://doi.org/10.1038/nrneph.2017.16

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