Nephrology and Hypertension Division, LSUHSC NO, New Orleans, LA 70112, USA.
Curr Hypertens Rep. 2012 Apr;14(2):177-81. doi: 10.1007/s11906-012-0250-2.
The prevalence of obesity in the United States remains high, exceeding 30% in most states. As this trend continues unhindered, we will continue see a persistent rise in obesity-related metabolic effects—hypertension, dyslipidemia, diabetes mellitus, and atherosclerosis. These diseases are also the leading causes of chronic kidney diseases and end-stage renal disease. The lipid nephrotoxicity hypothesis, proposed over three decades ago, suggested that proteinuria, decreased albumin levels, and the resultant hyperlipidemia may cause a glomerulosclerosis similar to atherosclerosis. More recent studies have demonstrated the role of oxidized high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles in the progression of kidney disease. Elucidation of the role of lipid-lowering therapies and the concomitant improvement in tubulointerstitial and glomerular diseases is a further evidence of the role of lipids in renal injury. Synergistic effects of lipid-lowering drugs and blockers of the renin-angiotensin-aldosterone system (RAAS) in renal protection have also been documented. Dyslipidemia in renal disease is usually characterized by elevated LDL cholesterol, low HDL cholesterol, and high triglycerides. After an initial glomerular injury, likely to be inflammatory, a series of self-perpetuating events occur. Increased glomerular basement permeability leads to loss of lipoprotein lipase activators, which results in hyperlipidemia. Circulating LDL has a charge affinity for glycoaminoglycans in the glomerular basement membrane and further increases its permeability. Substantial amounts of filtered lipoprotein cause proliferation of mesangial cells. Proximal tubules reabsorb some of the filtered lipoprotein, and the remainder is altered during passage through the nephron. If intraluminal pH is close to the isoelectric point of the apoprotein, luminal apoprotein will precipitate, causing tubulointerstitial disease. This review shows the evidence for the role of lipids in development of chronic renal disease, the pathophysiology of lipid nephrotoxicity, and strategies available to clinicians to slow the progression of disease.
美国的肥胖患病率仍然很高，大多数州的肥胖率超过 30%。随着这种趋势的持续发展，我们将继续看到肥胖相关代谢效应的持续上升——高血压、血脂异常、糖尿病和动脉粥样硬化。这些疾病也是慢性肾脏病和终末期肾病的主要原因。三十多年前提出的脂质肾毒性假说表明，蛋白尿、白蛋白水平降低以及由此导致的高脂血症可能导致类似于动脉粥样硬化的肾小球硬化。最近的研究表明，氧化高密度脂蛋白（HDL）和低密度脂蛋白（LDL）颗粒在肾脏病进展中的作用。阐明降脂治疗的作用以及肾小管间质和肾小球疾病的相应改善，进一步证明了脂质在肾损伤中的作用。降脂药物和肾素-血管紧张素-醛固酮系统（RAAS）阻滞剂的协同作用在肾脏保护中也有记录。肾脏病中的血脂异常通常表现为 LDL 胆固醇升高、HDL 胆固醇降低和甘油三酯升高。在初始肾小球损伤后，可能是炎症，一系列自我延续的事件发生。肾小球基底膜通透性增加导致脂蛋白脂肪酶激活剂丢失，导致高脂血症。循环 LDL 与肾小球基底膜中的糖胺聚糖具有电荷亲和力，进一步增加其通透性。大量滤过的脂蛋白导致系膜细胞增殖。近端小管重吸收部分滤过的脂蛋白，其余部分在通过肾单位时发生改变。如果管腔内 pH 接近载脂蛋白的等电点，管腔内载脂蛋白将沉淀，导致肾小管间质疾病。这篇综述表明了脂质在慢性肾脏病发展中的作用、脂质肾毒性的病理生理学以及临床医生可用于减缓疾病进展的策略的证据。
