Keane W F, Kasiske B L, O'Donnell M P, Schmitz P G
Department of Medicine, Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis 55415.
Am J Med. 1989 Nov;87(5N):21N-24N.
Progressive deterioration in renal function frequently occurs in the absence of the original cause of injury. During the past decade, intense investigations into the factors responsible for progressive nephron destruction have demonstrated that hemodynamic stresses and metabolic and coagulation abnormalities participate in glomerular injury. Hyperlipidemia is a common abnormality in renal disease and is frequently aggravated by protein-uria. Experimentally, therapy with the lipid-lowering agents clofibric acid or lovastatin reduced circulating lipids, particularly cholesterol, decreased proteinuria, and prevented glomerular damage in normotensive and hypertensive models of progressive renal disease. These beneficial effects occurred independently of changes in systemic blood pressure or glomerular injury, supporting the notion that cholesterol or its accompanying changes, or both, were central in lipid modulation of glomerulosclerosis. Clinically, lipid abnormalities are common in patients with renal disease, and atherosclerotic cardiovascular disease is the most frequent cause of death in these patients. Although the role of lipids in atherosclerotic disease has been well established, whether a similar effect of lipids occurs in the microvasculature of the kidney is unknown. Whether therapeutic approaches directed at reducing hyperlipidemia in patients with renal disease will provide a measure of renal protection, as has been seen in experimental models of renal disease, is also unknown.
在没有原始损伤原因的情况下，肾功能常出现进行性恶化。在过去十年中，对导致肾单位进行性破坏的因素进行的深入研究表明，血流动力学应激以及代谢和凝血异常参与了肾小球损伤。高脂血症是肾脏疾病中的常见异常情况，并且常因蛋白尿而加重。在实验中，使用降脂药物氯贝酸或洛伐他汀进行治疗可降低循环脂质，尤其是胆固醇，减少蛋白尿，并在进行性肾脏疾病的正常血压和高血压模型中预防肾小球损伤。这些有益作用的发生与全身血压或肾小球损伤的变化无关，这支持了胆固醇或其伴随变化，或两者兼而有之，在脂质调节肾小球硬化中起核心作用的观点。临床上，脂质异常在肾病患者中很常见，动脉粥样硬化性心血管疾病是这些患者最常见的死亡原因。尽管脂质在动脉粥样硬化疾病中的作用已得到充分证实，但脂质在肾脏微血管中是否产生类似作用尚不清楚。针对肾病患者降低高脂血症的治疗方法是否会像在肾病实验模型中看到的那样提供一定程度的肾脏保护作用，目前也不清楚。
