Filipiak Krzysztof J, Zawadzka-Byśko Maria
I Katedra i Klinika Kardiologii Akademii Medycznej w Warszawie.
Przegl Lek. 2005;62 Suppl 2:51-4.
Statins are the most frequently used lipid-lowering drugs in all cardiovascular disease. It has been postulated that also patients with renal failure and end-stage renal disease (ESRD) may benefit from statin therapy. Moreover, statins may exhibit additional inhibitory effects on the atherogenesis, such as a modulation of the immune system as triggered by oxidatively modified LDL and a reduction of the inflammatory marker C-reactive protein (CRP). Statins reduce inflammation, cell proliferation, which leads to a reduction in cellular damage. Those effects are probably independent of cholesterol levels. Limited data suggest that HMG-CoA reductase inhibitors (statins) may slow loss of renal function in individuals with chronic renal insufficiency. It is concluded on the basis of the CARE trial that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease, especially those with proteinuria. Similar data were obtained from recently published HPS trial with simvastatin. These findings require confirmation by a large randomized trial conducted specifically in people with chronic renal insufficiency. Statins vary in their pharmacological profiles, leading to distinct levels of systemic exposure and capacities to penetrate skeletal myocytes. Pharmacokinetic interactions with certain agents increase the likelihood of statin-induced myopathy and, in exceedingly rare instances, potentially fatal rhabdomyolysis with myoglobinuria and renal failure, therefore two statins have been suggested for renal failure patients. These are the ones that are not metabolised by the cytochrome P450 3A4 system--fluvastatin and pravastatin. The article summarizes the current therapeutic status of statin use in renal failure patients.
他汀类药物是所有心血管疾病中最常用的降脂药物。据推测，肾衰竭和终末期肾病（ESRD）患者也可能从他汀类药物治疗中获益。此外，他汀类药物可能对动脉粥样硬化形成具有额外的抑制作用，例如调节由氧化修饰的低密度脂蛋白引发的免疫系统以及降低炎症标志物C反应蛋白（CRP）。他汀类药物可减轻炎症、细胞增殖，从而减少细胞损伤。这些作用可能与胆固醇水平无关。有限的数据表明，HMG-CoA还原酶抑制剂（他汀类药物）可能会减缓慢性肾功能不全患者的肾功能丧失。基于CARE试验得出的结论是，普伐他汀可能会减缓中度至重度肾病患者，尤其是蛋白尿患者的肾功能丧失。从最近发表的辛伐他汀HPS试验中也获得了类似的数据。这些发现需要通过专门针对慢性肾功能不全患者进行的大型随机试验来证实。他汀类药物的药理特性各不相同，导致全身暴露水平和穿透骨骼肌细胞的能力不同。与某些药物的药代动力学相互作用增加了他汀类药物引起肌病的可能性，在极少数情况下，还可能导致潜在致命的伴有肌红蛋白尿和肾衰竭的横纹肌溶解，因此有人建议肾衰竭患者使用两种他汀类药物。它们是不通过细胞色素P450 3A4系统代谢的药物——氟伐他汀和普伐他汀。本文总结了他汀类药物在肾衰竭患者中的当前治疗状况。
