Department of Foundations of Medicine, New York University Long Island School of Medicine, Mineola, NY, USA.
Adv Exp Med Biol. 2022;1372:119-143. doi: 10.1007/978-981-19-0394-6_9.
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.
血浆中脂质和/或脂蛋白水平升高是动脉粥样硬化、非酒精性脂肪性肝病（NAFLD）、肥胖症和糖尿病的危险因素。这四种疾病也已被确定为导致慢性肾脏病（CKD）发展的危险因素。尽管已经确定了许多产生这些因素高血浆水平的途径，但大多数临床和生理功能障碍都源于脂蛋白的异常组装和分泌。几项已发表研究的结果表明，低密度脂蛋白（LDL）-胆固醇水平升高是动脉粥样硬化、心肌梗死、与 2 型糖尿病相关的冠状动脉钙化和 NAFLD 的危险因素。胆固醇代谢也被确定为导致 CKD 的重要途径；目前正在研究旨在改变胆固醇合成和代谢途径各个步骤的临床治疗方法。胆固醇的合成和分解代谢有助于一个多步骤的过程，该过程在肾脏组织的细胞水平上受到调节。胆固醇代谢也可能受到胆固醇分子内流和外流平衡的调节，这些分子能够穿过肾近端肾小管上皮细胞和足细胞的膜。胆固醇在细胞内的积累会导致脂毒性，最终导致肾功能障碍和衰竭。因此，需要进一步研究胆固醇代谢途径，以加深我们对胆固醇限制影响的理解，目前这是推荐给血脂异常患者的主要干预措施。
