Crosstalk between kidney and liver in non-alcoholic fatty liver disease: mechanisms and therapeutic approaches

Abstract

Liver and kidney are vital organs that maintain homeostasis and injury to either of them triggers pathogenic pathways affecting the other. For example, non-alcoholic fatty liver disease (NAFLD) promotes the progression of chronic kidney disease (CKD), vice versa acute kidney injury (AKI) endorses the induction and progression of liver dysfunction. Progress in clinical and basic research suggest a role of excessive fructose intake, insulin resistance, inflammatory cytokines production, activation of the renin–angiotensin system, redox imbalance, and their impact on epigenetic regulation of gene expression in this context. Recent developments in experimental and clinical research have identified several biochemical and molecular pathways for AKI-liver interaction, including altered liver enzymes profile, metabolic acidosis, oxidative stress, activation of inflammatory and regulated cell death pathways. This review focuses on the current preclinical and clinical findings on kidney–liver crosstalk in NAFLD-CKD and AKI-liver dysfunction settings and highlights potential molecular mechanisms and therapeutic targets.

Keywords:

• Non-alcoholic fatty liver disease
• chronic kidney disease
• crosstalk
• acute kidney injury
• liver dysfunction

Acknowledgements

A. B. G. sincerely acknowledges the financial support obtained from the Science & Engineering Research Board – Department of Science & Technology (SERB-DST), Govt. of India [SERB/ECR/2017/000317] for his research work. H. J. A. was supported by the Deutsche Forschungsgemeinschaft (AN372/14-3, 23-1, 24-1, 27-1).

Author contributions

N. S. conducted literature research, designed and wrote the manuscript. A. S. co-wrote the manuscript. H. J. A. participated to design the manuscript, edited and prepared it for submission. A. B. G. designed and drafted the manuscript. All authors read and approved the final manuscript.

Disclosure statement

The authors declare no potential conflicts of interest.