Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, California, USA.
J Ren Nutr. 2010 Sep;20(5 Suppl):S35-43. doi: 10.1053/j.jrn.2010.05.010.
Chronic kidney disease (CKD) is associated with a high risk of death from cardiovascular disease. Inflammation, oxidative stress, and dyslipidemia, which are common consequences of CKD, contribute to the pathogenesis of atherosclerosis and cardiovascular disease in this population. Dyslipidemia of CKD is characterized by diminished plasma high density lipoprotein (HDL) concentration, impaired HDL anti-oxidant and anti-inflammatory activities, and elevated plasma triglyceride, very low density lipoprotein (VLDL), intermediate density lipoprotein, chylomicron remnants, and oxidized lipids and lipoproteins. The constellation of inflammation, HDL deficiency, and oxidative modification of lipoproteins can cause atherosclerosis and progression of renal disease. We have recently found lipid accumulation in the remnant kidney and the wall of aorta in rats with CKD induced by 5/6 nephrectomy. This was mediated by up-regulation of scavenger receptors involved in the influx of oxidized lipids or lipoproteins, tubular reabsorption of lipid binding proteins through megalin-cubilin complexes, upregulation of fatty acid synthesis, and downregulation of fatty acid oxidation pathways. The combination of increased lipid influx, elevated production and reduced catabolism of lipids, and impaired HDL-mediated reverse cholesterol transport can promote atherosclerosis, glomerulosclerosis, and tubulointerstitial damage. Although statins can be effective in slowing CKD progression in patients with mild-to-moderate CKD, they have consistently failed to mitigate oxidative stress, inflammation, HDL deficiency, or cardiovascular mortality in the end-stage renal disease populations. Similarly, high doses of antioxidant vitamins have failed to either ameliorate oxidative stress, inflammation, or improve overall mortality in end-stage renal disease. This article is intended to provide a brief review of the effects of CKD on HDL structure and function and pathways of lipid influx, efflux, synthesis, and catabolism in the artery wall and the diseased kidney.
慢性肾脏病(CKD)与心血管疾病死亡风险增加有关。炎症、氧化应激和血脂异常是 CKD 的常见后果,它们导致了该人群的动脉粥样硬化和心血管疾病的发病机制。CKD 的血脂异常表现为血浆高密度脂蛋白(HDL)浓度降低、HDL 抗氧化和抗炎活性受损,以及血浆甘油三酯、极低密度脂蛋白(VLDL)、中间密度脂蛋白、乳糜微粒残基和氧化脂质和脂蛋白升高。炎症、HDL 缺乏和脂蛋白氧化修饰的组合可导致动脉粥样硬化和肾脏疾病的进展。我们最近发现,在 5/6 肾切除诱导的 CKD 大鼠的残余肾脏和主动脉壁中存在脂质积累。这是通过参与氧化脂质或脂蛋白内流的清道夫受体的上调、通过巨球蛋白-穹窿素复合物进行的脂质结合蛋白的管状重吸收、脂肪酸合成的上调以及脂肪酸氧化途径的下调来介导的。脂质内流增加、脂质产生和分解代谢减少以及 HDL 介导的胆固醇逆转运受损的组合可促进动脉粥样硬化、肾小球硬化和小管间质损伤。虽然他汀类药物在减缓轻中度 CKD 患者的 CKD 进展方面可能有效,但它们始终未能减轻氧化应激、炎症、HDL 缺乏或终末期肾病患者的心血管死亡率。同样,大剂量抗氧化维生素也未能改善氧化应激、炎症或改善终末期肾病患者的总死亡率。本文旨在简要综述 CKD 对 HDL 结构和功能的影响,以及动脉壁和病变肾脏中脂质内流、外流、合成和分解代谢的途径。
Blood Purif. 2011-1-10
J Ren Nutr. 2009-1
Am J Physiol Renal Physiol. 2006-2
Nat Rev Nephrol. 2010-3-23
Panminerva Med. 2006-9
Clin Sci (Lond). 2009-1
Int J Mol Sci. 2025-2-16
Sci Rep. 2024-6-27
Kidney Int Rep. 2023-11-29