极高剂量缬沙坦对2型糖尿病患者蛋白尿的影响

目的探讨高剂量缬沙坦对降低2型糖尿病患者尿白蛋白排泄率（UAER）的疗效是否优于常规剂量的缬沙坦。方法连续人选2010年6月～2012年11月在我院内科门诊就诊的391例高血压合并2型糖尿病和蛋白尿的患者，随机分为160rag、320mg和640mg缬沙坦组。前4周所有患者均服用缬沙坦160rag。在之后的30周内，其中2组增加缬沙坦的剂量。分别采用基线、4周、16周和30周时收集的过夜尿（一式三份）来评估蛋白尿。结果在第4周时，各组的白蛋白尿均显著减少（P〈0．001），之后，缬沙坦320mg组和640mg组的白蛋白尿出现非常显著地减少（P〈0．001），而160mg组只有中等程度的进一步减少（P=-0．03）。至30周时，缬沙坦640mg组白蛋白尿恢复正常的患者比例是160mg组的2倍（P〈0．01）。高剂量组患者的耐受性良好．未出现与剂量增加相关的不良事件（包括低血压和高钾血症）。结论高剂量缬沙坦减少白蛋白尿的疗效优于常用剂量160mg．且明显与血压无关。因此，至少2型糖尿病患者需要较高剂量的缬沙坦，这不是为了控制血压．而是要获得最佳的组织保护。

Albuminuria response to very high-dose valsartan in type 2 diabetes mellitus

Objective To investigate whether high doses of valsartan being superior to conventional doses to reduce uri- nary albumin excretion rates （UAER） in such patients. Methods 391 hypertensive patients with type 2 diabetes mellitus and UAER were randomized to 160mg, 320mg or 640mg valsartan groups. All received valsartan 160mg for the first 4 weeks. Val- sartan dose was then increased in two of three groups for 30 weeks. Overnight urine collections at baseline, 4, 16 and 30 weeks in triplicate were used to assess albuminuria. Results Comparable albuminuria reductions occurred in all groups at the 4th week（P〈0.001 ）. Subsequently, a highly significant albuminuria fall occurred with valsartan 320rag and 640mg groups （P〈0.001） versus a modest additional change with 160rag group （P=0.03）. At the 30th week, twice as many patients returned to normal al- buminuria with valsartan 640mg versus 160rag （P〈0.01）. High doses were well tolerated, with no dose-related increases in ad- verse events, including hypotension and hyperkalemia. Conclusion High doses of valsartan reduce albuminuria more than 160 mg dose, apparently independent of blood pressure. Thus, at least in type 2 diabetes mellitus, higher doses of valsartan are required to optimize tissue protection than for blood pressure control.