Asberg A, Hartmann A, Fjeldså E, Holdaas H
Laboratory for Renal Physiology, Section of Nephrology, Medical Department, The National Hospital, N-0027 Oslo, Norway.
Nephrol Dial Transplant. 2001 Sep;16(9):1920-4. doi: 10.1093/ndt/16.9.1920.
Hyperlipidaemia and endothelial dysfunction are common features in cyclosporin A (CsA)-treated renal transplant recipients. Endothelial dysfunction may contribute to the risk of premature atherosclerosis and cardiovascular death in these patients. A beneficial effect of statin therapy beyond cholesterol lowering may be an improvement of endothelial function. The present study was designed to assess the effect of atorvastatin on serum lipids and endothelial function in CsA treated renal transplant recipients.
This pilot study was an open trial of 4 weeks atorvastatin (10 mg per day) treatment in renal transplant recipients (n=22). All patients received a CsA- and prednisolone-based immunosuppressive regimen. Endothelial function was assessed in the forearm skin microvasculature by acetylcholine stimulation and laser Doppler flowmetry, before and after atorvastatin treatment. Serum lipids, plasma endothelin-1 (ET-1), nitric oxide (NO), and von Willebrand factor (vWF) were also measured.
Both total and LDL cholesterol were significantly reduced by 26.8 +/- 8.4 and 41.5 +/- 11.0% respectively, after 4 weeks of treatment. Endothelial function was significantly improved during atorvastatin treatment, area under the flux versus time curve (AUC)(ACh) was 538 +/- 362 AU x min before and 682 +/- 276 AU x min after treatment (P=0.042). Plasma NO levels also showed a borderline significant increase from 49 +/- 30 to 57 +/- 37 micromol/l during the treatment period (P=0.051), though plasma ET-1 (0.37+/-0.08 vs 0.37+/-0.12 fmol/ml) and vW (196+/-57 vs 197+/-37%) were unchanged.
Atorvastatin lowered serum cholesterol significantly and improved endothelial function in renal transplant recipients after 4 weeks of treatment. Plasma NO levels were increased during atorvastatin treatment, indicating a possible endothelial protective effect through an "endothelial-NO pathway".
高脂血症和内皮功能障碍是接受环孢素A（CsA）治疗的肾移植受者的常见特征。内皮功能障碍可能会增加这些患者过早发生动脉粥样硬化和心血管死亡的风险。他汀类药物治疗除了降低胆固醇外，其有益作用可能还包括改善内皮功能。本研究旨在评估阿托伐他汀对接受CsA治疗的肾移植受者血脂和内皮功能的影响。
本前瞻性研究是一项针对肾移植受者（n = 22）进行的为期4周的阿托伐他汀（每日10毫克）开放试验。所有患者均接受基于CsA和泼尼松龙的免疫抑制方案。在阿托伐他汀治疗前后，通过乙酰胆碱刺激和激光多普勒血流仪评估前臂皮肤微血管的内皮功能。还测量了血脂、血浆内皮素-1（ET-1）、一氧化氮（NO）和血管性血友病因子（vWF）。
治疗4周后，总胆固醇和低密度脂蛋白胆固醇分别显著降低了26.8±8.4%和41.5±11.0%。在阿托伐他汀治疗期间，内皮功能显著改善，通量与时间曲线下面积（AUC）（ACh）在治疗前为538±362 AU·min，治疗后为682±276 AU·min（P = 0.042）。治疗期间血浆NO水平也有临界显著升高，从49±30微摩尔/升升至57±37微摩尔/升（P = 0.051），而血浆ET-1（0.37±0.08对0.37±0.12飞摩尔/毫升）和vWF（196±57对197±37%）未发生变化。
阿托伐他汀治疗4周后可显著降低肾移植受者的血清胆固醇并改善内皮功能。阿托伐他汀治疗期间血浆NO水平升高，表明可能通过“内皮-NO途径”产生内皮保护作用。
