Pathological Connections between Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease

Abstract

Background: Non-alcoholic fatty liver disease and chronic kidney disease are major public health issues worldwide. The clinical burden of non-alcoholic 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 non-alcoholic fatty liver disease and chronic kidney disease, independent of the identified cardiorenal risk factors. The presence and severity of non-alcoholic fatty liver disease are related to the developmental stage and risk of chronic kidney disease. And chronic kidney disease progression also contributes to non-alcoholic fatty liver disease development. Non-alcoholic fatty liver disease and chronic kidney disease mutually contribute to disease progression through pathological links. Shared pathogenic mechanisms also exist between non-alcoholic 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 non-alcoholic fatty liver disease and chronic kidney disease and shared pathogenic mechanisms to find novel targeted therapies and retard the progression of both disease processes.

Chronic kidney disease and the severity of non-alcoholic fatty liver disease: a systematic review

“…Table 1 presents the main characteristics of the included studies. The presence of NAFLD was found to be associated with the presence of CKD in four studies [13][14][15][16] , and the development of NAFLD was found to increase the risk of CKD incidence in four additional studies [17][18][19][20] . In these eight studies [13][14][15][16][17][18][19][20] , the severity of liver disease was associated with a reduction in kidney function, regardless of known risk factors.…”

“…The presence of NAFLD was found to be associated with the presence of CKD in four studies [13][14][15][16] , and the development of NAFLD was found to increase the risk of CKD incidence in four additional studies [17][18][19][20] . In these eight studies [13][14][15][16][17][18][19][20] , the severity of liver disease was associated with a reduction in kidney function, regardless of known risk factors. Two studies did not find an association between NAFLD and CKD nor an increase in the incidence of CKD after adjusting for metabolic syndrome elements.…”

“…It is possible that only those with more advanced NAFLD, particularly with NASH or liver fibrosis, may be at increased risk for CKD. More recently, cross-sectional studies with a large number of individuals 20,14 and long-term cohorts 17 have confirmed that NAFLD is an independent risk factor for CKD. Zuo et al 19 confirmed this hypothesis but suggested that the progression of liver fibrosis in individuals with NAFLD is a more significant predictor for the development of CKD than baseline levels of metabolic diseases.…”

Association of NAFLD/NASH, and MAFLD/MASLD with chronic kidney disease: an updated narrative review

“…Over the last few years, cross-sectional studies and one meta-analysis of cross-sectional studies have evaluated the association between NAFLD/MAFLD/MASLD and CKD, such as summarized in Table 2 [44][45][46][47][48][49][50] .…”

“…Studies summarized in Table 2 have yielded discrepant or conflicting findings, which probably occur owing to limited patient populations and may be explained by variable strength of association with CKD of NAFLD vs. MAFLD. Of interest, the two meta-analytic reviews by Musso et al and Agustanti et al found that NAFLD and MAFLD, respectively, were associated with a significantly higher prevalence of CKD [44,50] .…”