Influence of Nonalcoholic Fatty Liver Disease on the Occurrence and Severity of Chronic Kidney Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is reported to affect 20-30% of adults and is accompanied by various metabolic comorbidities, where the economic and clinical burden of NAFLD is attributed to the progression of liver disease as well as the presence of extrahepatic diseases. Chronic kidney disease (CKD), which has a high incidence rate, high morbidity and mortality rates, and high medical costs, has been linked to NAFLD. CKD is associated with some metabolism-related risk factors that overlap with metabolic comorbidities of NAFLD. Therefore, to investigate the potential factors that influence CKD occurrence, the association between NAFLD and CKD should be clarified. Some studies have confirmed that NAFLD influences the occurrence and severity of CKD, whereas some studies have indicated that there is no correlation. In this review, the results of a few studies have been discussed, the potential risk factors for CKD in NAFLD are explored, and the respective biological mechanisms are elaborated to help clinicians identify CKD in patients much earlier than it is diagnosed now and thus help in reducing the incidence of liver and kidney transplants.

MAFLD and CKD: An Updated Narrative Review

“…Over the last decades, several epidemiological studies and some meta-analyses have clearly reported that NAFLD (detected by blood biomarkers/scores, imaging techniques, International Classification of Diseases codes or liver biopsy) is associated with an increased risk of incident CKD, independent of established CKD risk factors, diabetes-related variables and other potential confounders [21][22][23][24][25]. Notably, as previously mentioned, the association between NAFLD and CKD have relevant clinical implications, as both NAFLD and CKD are two important global health problems with the worryingly direction to become more and more frequent worldwide [21].…”

“…In literature, several narrative reviews have already described the biological mechanisms underpinning the association between NAFLD/MAFLD and the risk of CKD [21,[23][24][25]. Here, we will limit ourselves to describing the salient aspects of this topic (Figure 1).…”

“…Here, we will limit ourselves to describing the salient aspects of this topic (Figure 1). Growing experimental and clinical evidence indicates that NAFLD/MAFLD and its advanced forms exacerbate (a) the systemic insulin resistance (via the secretion of hepatokines, such as fibroblast growth factor-21), (b) the atherogenic dyslipidaemia and hypertension, (c) the activation of the renin-angiontensin system (RAS) which, in turn, is associated with endothelial dysfunction, and (d) the release, into the bloodstream, of several mediators able to promote a chronic pro-inflammatory and pro-coagulant state [21,[23][24][25]. All these factors may play a role in the pathophysiology of CKD [21,[23][24][25].…”

“…Growing experimental and clinical evidence indicates that NAFLD/MAFLD and its advanced forms exacerbate (a) the systemic insulin resistance (via the secretion of hepatokines, such as fibroblast growth factor-21), (b) the atherogenic dyslipidaemia and hypertension, (c) the activation of the renin-angiontensin system (RAS) which, in turn, is associated with endothelial dysfunction, and (d) the release, into the bloodstream, of several mediators able to promote a chronic pro-inflammatory and pro-coagulant state [21,[23][24][25]. All these factors may play a role in the pathophysiology of CKD [21,[23][24][25]. In addition, interestingly, preliminary studies also indicate that some specific genetic polymorphisms, especially rs738409 C>G p.I148M in the PNPLA3 (patatin-like phospholipase domaincontaining protein 3) gene, have an important role in the development and progression of NAFLD [47], MAFLD [48], but also a potential role in the development of kidney abnormalities [23,49].…”

“…Other potential genetic polymorphisms associated with NAFLD and potentially linked to kidney abnormalities are described in detail in the 2022 review by Wang et al [23]. A better comprehension of these complex biological mechanisms may lead to novel targets for the treatment of NAFLD/MAFLD but also of CKD [21,[23][24][25].…”