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World J Gastroenterol. Oct 21, 2022; 28(39): 5691-5706
Published online Oct 21, 2022. doi: 10.3748/wjg.v28.i39.5691
Interplay between metabolic dysfunction-associated fatty liver disease and chronic kidney disease: Epidemiology, pathophysiologic mechanisms, and treatment considerations
Panagiotis Theofilis, Aikaterini Vordoni, Rigas G Kalaitzidis
Panagiotis Theofilis, Aikaterini Vordoni, Rigas G Kalaitzidis, Center for Nephrology “G. Papadakis,” General Hospital of Nikaia-Piraeus “Agios Panteleimon,” Nikaia 18454, Greece
Author contributions: Theofilis P contributed to conceiving the study; Theofilis P and Vordoni A contributed to the investigation; Theofilis P contributed to the visualization; Kalaitzidis RG contributed to the supervision; Theofilis P and Vordoni A wrote the original draft; Kalaitzidis RG edited the original draft; All authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Panagiotis Theofilis, MD, Doctor, Researcher, Center for Nephrology “G. Papadakis,” General Hospital of Nikaia-Piraeus “Agios Panteleimon,” Piraeus, Nikaia 18454, Greece.
Received: August 12, 2022
Peer-review started: August 12, 2022
First decision: August 29, 2022
Revised: September 6, 2022
Accepted: September 19, 2022
Article in press: September 19, 2022
Published online: October 21, 2022

The recently proposed nomenclature change from non-alcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease (MAFLD) has resulted in the reappraisal of epidemiological trends and associations with other chronic diseases. In this context, MAFLD appears to be tightly linked to incident chronic kidney disease (CKD). This association may be attributed to multiple shared risk factors including type 2 diabetes mellitus, arterial hypertension, obesity, dyslipidemia, and insulin resistance. Moreover, similarities in their molecular pathophysiologic mechanisms can be detected, since inflammation, oxidative stress, fibrosis, and gut dysbiosis are highly prevalent in these pathologic states. At the same time, lines of evidence suggest a genetic predisposition to MAFLD due to gene polymorphisms, such as the PNPLA3 rs738409 G allele polymorphism, which may also propagate renal dysfunction. Concerning their management, available treatment considerations for obesity (bariatric surgery) and novel antidiabetic agents (glucagon-like peptide 1 receptor agonists, sodium-glucose co-transporter 2 inhibitors) appear beneficial in preclinical and clinical studies of MAFLD and CKD modeling. Moreover, alternative approaches such as melatonin supplementation, farnesoid X receptor agonists, and gut microbiota modulation may represent attractive options in the future. With a look to the future, additional adequately sized studies are required, focusing on preventing renal complications in patients with MAFLD and the appropriate management of individuals with concomitant MAFLD and CKD.

Keywords: Metabolic dysfunction-associated fatty liver disease, Chronic kidney disease, Hepatic steatosis, inflammation, Type 2 diabetes mellitus, Obesity

Core Tip: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently defined pathological state aiming to identify individuals at increased risk of adverse prognosis. Numerous epidemiological studies propose that chronic kidney disease may be among its complications. Their shared risk factors, molecular mechanisms, and genetic predisposition represent the basis for this relationship. Accordingly, treatment approaches with combined efficacy in MAFLD and chronic renal impairment are expected to positively impact the natural history of this deleterious interaction, which remains to be confirmed in future studies.