Cholesterol Metabolism in Chronic Kidney Disease: Physiology, Pathologic Mechanisms, and Treatment

Abstract

High plasma levels of lipids and/or lipoproteins are risk factors for atherosclerosis, nonalcoholic fatty liver disease (NAFLD), obesity, and diabetes. These four conditions have also been identified as risk factors leading to the development of chronic kidney disease (CKD). Although many pathways that generate high plasma levels of these factors have been identified, most clinical and physiologic dysfunction results from aberrant assembly and secretion of lipoproteins. The results of several published studies suggest that elevated levels of low-density lipoprotein (LDL)-cholesterol are a risk factor for atherosclerosis, myocardial infarction, coronary artery calcification associated with type 2 diabetes, and NAFLD. Cholesterol metabolism has also been identified as an important pathway contributing to the development of CKD; clinical treatments designed to alter various steps of the cholesterol synthesis and metabolism pathway are currently under study. Cholesterol synthesis and catabolism contribute to a multistep process with pathways that are regulated at the cellular level in renal tissue. Cholesterol metabolism may also be regulated by the balance between the influx and efflux of cholesterol molecules that are capable of crossing the membrane of renal proximal tubular epithelial cells and podocytes. Cellular accumulation of cholesterol can result in lipotoxicity and ultimately kidney dysfunction and failure. Thus, further research focused on cholesterol metabolism pathways will be necessary to improve our understanding of the impact of cholesterol restriction, which is currently a primary intervention recommended for patients with dyslipidemia.