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      Pathological Connections between Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease

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          Abstract

          Background

          Nonalcoholic fatty liver disease and chronic kidney disease are major public health issues worldwide. The clinical burden of nonalcoholic fatty liver disease is not only confined to liver-related morbidity and mortality, but it also includes the burden of chronic extrahepatic complications. It is well known that liver and kidney are strictly interconnected in physiological and pathological conditions.

          Summary

          Mounting evidence indicates a strong association between nonalcoholic fatty liver disease and chronic kidney disease, independent of the identified cardiorenal risk factors. The presence and severity of nonalcoholic fatty liver disease are related to the developmental stage and risk of chronic kidney disease. And chronic kidney disease progression also contributes to nonalcoholic fatty liver disease development. Nonalcoholic fatty liver disease and chronic kidney disease mutually contribute to disease progression through pathological links. Shared pathogenic mechanisms also exist between nonalcoholic fatty liver disease and chronic kidney disease, including pyroptosis and ferroptosis. Additionally, the use of combined liver-kidney transplantation has increased exponentially in recent years.

          Key Messages

          This review focuses on the emerging pathological mechanisms linking nonalcoholic fatty liver disease and chronic kidney disease and shared pathogenic mechanisms to find novel targeted therapies and retard the progression of both disease processes.

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          Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

          Zobair Younossi, Quentin M Anstee, Milena Marietti … (2018)
          NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.
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            NAFLD: a multisystem disease.

            Christopher Byrne, Giovanni Targher (2015)
            Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords "non-alcoholic fatty liver disease" or "fatty liver" combined with "diabetes", "cardiovascular (or cardiac) disease", "cardiovascular mortality" or "chronic kidney disease" between 1990 and 2014. Articles published in languages other than English were excluded.
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              Global Perspectives on Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis

              Zobair Younossi, Frank Tacke, Marco Arrese … (2018)
              Over the past 2 decades, nonalcoholic fatty liver disease (NAFLD) has grown from a relatively unknown disease to the most common cause of chronic liver disease in the world. In fact, 25% of the world's population is currently thought to have NAFLD. Nonalcoholic steatohepatitis (NASH) is the subtype of NAFLD that can progress to cirrhosis, hepatocellular carcinoma (HCC), and death. NAFLD and NASH are not only found in adults-there is also a high prevalence of these diseases in children and adolescents. Because of the close association of NAFLD with type 2 diabetes (T2DM) and obesity, the latest models predict that the prevalence of NAFLD and NASH will increase, causing a tremendous clinical and economic burden and poor patient-reported outcomes. Nonetheless, there is no accurate noninvasive method to detect NASH, and treatment of this disease is limited to lifestyle modifications. To examine the state of NAFLD among different regions and understand the global trajectory of this disease, an international group of experts came together during the 2017 American Association for the Study of Liver Diseases Global NAFLD Forum. We provide a summary of this forum and an assessment of the current state of NAFLD and NASH worldwide.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Kidney Dis (Basel)
                Journal ID (iso-abbrev): Kidney Dis (Basel)
                Journal ID (publisher-id): KDD
                Title: Kidney Diseases
                Publisher: S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                ISSN (Print): 2296-9381
                ISSN (Electronic): 2296-9357
                Publication date Collection: December 2022
                Publication date (Electronic): 31 October 2022
                Publication date PMC-release: 31 October 2022
                Volume: 8
                Issue: 6
                Pages: 458-465
                Affiliations
                Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                Author notes
                Article
                Publisher ID: kdd-0008-0458
                DOI: 10.1159/000527834
                PMC ID: 9798839
                PubMed ID: 36590682
                SO-VID: 262dc4b4-d4f6-4ed2-8ea0-39ab5f684813
                Copyright © Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.

                History
                Date received : 9 April 2022
                Date accepted : 22 September 2022
                Date: 2022
                Page count
                References: 92, Pages: 8
                Funding
                This research was funded by the National Natural Science Foundation of China (grant number: 81770736).
                Categories
                Subject: Review Article

                Keywords: nonalcoholic fatty liver disease,chronic kidney disease,pathogenic mechanisms,interaction,common pathway
                Data availability:
                Keywords: nonalcoholic fatty liver disease, chronic kidney disease, pathogenic mechanisms, interaction, common pathway

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