Paulsen Lone, Holm Charlotte, Bech Jesper Nørgaard, Starklint Jørn, Pedersen Erling Bjerregaard
Department of Medical Research, Holstebro Hospital, Laegårdvej 12, DK-7500 Holstebro, Denmark.
Nephrol Dial Transplant. 2008 May;23(5):1556-61. doi: 10.1093/ndt/gfm807. Epub 2007 Dec 8.
Statins have a beneficial effect on cardiovascular morbidity and mortality due to a reduction in plasma cholesterol. However, statins seem to have effects beyond the lowering of plasma cholesterol. We hypothesize that these effects are caused by an effect on renal function.
We measured the effects of atorvastatin (AS) on renal function in two randomized, placebo-controlled, double-blinded and crossover studies in healthy man. In an acute trial (Study 1), 19 subjects received either 80 mg AS as a single dose or placebo. In a short-term trial (Study 2), 20 subjects received either 80 mg AS or placebo daily for 4 weeks. In both studies glomerular filtration rate (GFR), renal plasma flow (RPF), plasma concentrations of angiotensin II (Ang II), renin (PRC), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), aldosterone (Aldo), vasopressin (AVP) and blood pressure (BP) were determined.
In Study 1 AS decreased fractional excretion of sodium (FE(Na)) significantly (P = 0.035), but very modestly, and reduced diastolic BP (P = 0.024). Apart from this, we found no significant differences in GFR, RPF, tubular function and vasoactive hormones in either Study 1 or 2.
An acute dose of AS decreased FE(Na) and DBP in healthy humans. The reduction in fractional urinary sodium excretion was very modest and transitory, and most likely secondary to the fall in diastolic blood pressure (DBP). However, renal haemodynamics, tubular function, vasoactive hormones and blood pressure were unchanged during short-term statin treatment in healthy man.
他汀类药物因降低血浆胆固醇而对心血管疾病的发病率和死亡率具有有益作用。然而，他汀类药物的作用似乎超出了降低血浆胆固醇的范畴。我们推测这些作用是由对肾功能的影响所致。
在两项针对健康男性的随机、安慰剂对照、双盲交叉研究中，我们测定了阿托伐他汀（AS）对肾功能的影响。在一项急性试验（研究1）中，19名受试者接受单次80mg AS或安慰剂治疗。在一项短期试验（研究2）中，20名受试者每天接受80mg AS或安慰剂治疗，为期4周。在两项研究中均测定了肾小球滤过率（GFR）、肾血浆流量（RPF）、血管紧张素II（Ang II）、肾素（PRC）、心房利钠肽（ANP）、脑利钠肽（BNP）、醛固酮（Aldo）、血管加压素（AVP）的血浆浓度以及血压（BP）。
在研究1中，AS显著降低了钠的分数排泄（FE(Na)）（P = 0.035），但降低幅度非常小，同时降低了舒张压（P = 0.024）。除此之外，我们在研究1或研究2中均未发现GFR、RPF、肾小管功能和血管活性激素方面的显著差异。
急性剂量的AS可降低健康人的FE(Na)和舒张压。尿钠分数排泄的降低幅度非常小且短暂，很可能是舒张压下降的继发结果。然而，在健康男性短期他汀类药物治疗期间，肾血流动力学、肾小管功能、血管活性激素和血压均未改变。
