Institute for Molecular Cardiovascular Research, RWTH Aachen University, University Hospital, Aachen, Germany.
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
Nat Rev Nephrol. 2021 Aug;17(8):528-542. doi: 10.1038/s41581-021-00423-5. Epub 2021 May 10.
Chronic kidney disease (CKD) induces modifications in lipid and lipoprotein metabolism and homeostasis. These modifications can promote, modulate and/or accelerate CKD and secondary cardiovascular disease (CVD). Lipid and lipoprotein abnormalities - involving triglyceride-rich lipoproteins, LDL and/or HDL - not only involve changes in concentration but also changes in molecular structure, including protein composition, incorporation of small molecules and post-translational modifications. These alterations modify the function of lipoproteins and can trigger pro-inflammatory and pro-atherogenic processes, as well as oxidative stress. Serum fatty acid levels are also often altered in patients with CKD and lead to changes in fatty acid metabolism - a key process in intracellular energy production - that induce mitochondrial dysfunction and cellular damage. These fatty acid changes might not only have a negative impact on the heart, but also contribute to the progression of kidney damage. The presence of these lipoprotein alterations within a biological environment characterized by increased inflammation and oxidative stress, as well as the competing risk of non-atherosclerotic cardiovascular death as kidney function declines, has important therapeutic implications. Additional research is needed to clarify the pathophysiological link between lipid and lipoprotein modifications, and kidney dysfunction, as well as the genesis and/or progression of CVD in patients with kidney disease.
慢性肾脏病（CKD）会引起脂质和脂蛋白代谢及平衡的改变。这些改变可促进、调节和/或加速 CKD 及继发性心血管疾病（CVD）的发生。脂质和脂蛋白异常——涉及富含甘油三酯的脂蛋白、LDL 和/或 HDL——不仅涉及浓度的变化，还涉及分子结构的变化，包括蛋白质组成、小分子的掺入和翻译后修饰。这些改变会改变脂蛋白的功能，并可引发促炎和促动脉粥样硬化过程以及氧化应激。CKD 患者的血清脂肪酸水平也常常发生改变，导致脂肪酸代谢的改变——这是细胞内能量产生的关键过程——从而诱导线粒体功能障碍和细胞损伤。这些脂肪酸的改变不仅可能对心脏产生负面影响，而且可能导致肾脏损伤的进展。在炎症和氧化应激增加的生物学环境中存在这些脂蛋白改变，以及随着肾功能下降非动脉粥样硬化性心血管死亡的竞争风险，具有重要的治疗意义。需要进一步的研究来阐明脂质和脂蛋白改变与肾功能障碍以及肾脏病患者 CVD 的发生和/或进展之间的病理生理联系。
