Lipid Disorders in NAFLD and Chronic Kidney Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver dysfunction and is characterized by exaggerated lipid accumulation, inflammation and even fibrosis. It has been shown that NAFLD increases the risk of other chronic diseases, particularly chronic kidney disease (CKD). Lipid in excess could lead to liver and kidney lesions and even end-stage disease through diverse pathways. Dysregulation of lipid uptake, oxidation or de novo lipogenesis contributes to the toxic effects of ectopic lipids which promotes the development and progression of NAFLD and CKD via triggering oxidative stress, apoptosis, pro-inflammatory and profibrotic responses. Importantly, dyslipidemia and release of pro-inflammatory cytokines caused by NAFLD (specifically, nonalcoholic steatohepatitis) are considered to play important roles in the pathological progression of CKD. Growing evidence of similarities between the pathogenic mechanisms of NAFLD and those of CKD has attracted attention and urged researchers to discover their common therapeutic targets. Here, we summarize the current understanding of molecular aberrations underlying the lipid metabolism of NAFLD and CKD and clinical evidence that suggests the relevance of these pathways in humans. This review also highlights the orchestrated inter-organ cross-talk in lipid disorders, as well as therapeutic options and opportunities to counteract NAFLD and CKD.

Association of metabolic dysfunction-associated fatty liver disease with chronic kidney disease: a Chinese population-based study

“…Liver–kidney crosstalk in MAFLD includes alterations in the renin-angiotensin system (RAS), insulin resistance and activated protein kinase (AMPK) activation, impaired antioxidant defenses, and excessive dietary fructose intake, which affects kidney injury by altering lipogenesis and inflammatory responses [ 35 , 36 ]. Moreover, the insulin resistance involved in MAFLD can in turn aggravate lipid metabolism disorders, forming a vicious cycle.…”

“…To date, rare large studies on the pharmacological or nonpharmacological treatment of MAFLD patients with CKD have been reported [ 35 ]. However, because MAFLD and CKD share several common risk factors (e.g.…”

“…obesity, insulin resistance, dyslipidemia, hypertension, and dysglycemia) and pathogenetic pathways, current management of MAFLD patients with CKD focuses on lipid and glucose lowering, blood pressure control, and weight loss [ 35 ]. Several studies have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, farnesoid X nuclear receptor (FXR) agonists, thyroid hormone receptor β (TR β) agonists and proprotein convertase subtilisin-kex in type 9 (PCSK9) inhibitors may be promising agents for the treatment of MAFLD patients with CKD [ 35 , 45 ]. Additionally, modulation of gut microbial components and mesenchymal stem cells (MSCs)-based therapy may be novel therapeutic strategies for MAFLD and CKD [ 46 , 47 ].…”

Pathological Connections between Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease

“…NAFLD is characterized by exaggerated lipid accumulation, and dyslipidemia and release of pro-inflammatory cytokines are considered to play an important role in the pathological progression of CKD [ 26 ]. There is increasing evidence to suggest that ectopic lipid deposition plays a key role in accelerating the progression of NAFLD and CKD [ 27 ].…”

The Roles of Fatty Acids and Apolipoproteins in the Kidneys

“…Lipid droplets are observed in the renal cells of obese people [ 69 ]. Renal metabolic deregulation aggravates lipid deposition, thus leading to a decrease in energy expenditure that ultimately induces apoptosis and contributes to CKD [ 70 ]. The activation of PPARγ by PPARγ agonists is a lipolytic mechanism protective against kidney changes caused by obesity [ 71 ].…”