Shahinfar Shahnaz, Dickson Tania Z, Ahmed Tultul, Zhang Zhonxin, Ramjit Denise, Smith Ronald D, Brenner Barry M
Merck and Co., Inc., West Point, Pennsylvania 19486, USA.
Kidney Int Suppl. 2002 Dec(82):S64-7. doi: 10.1046/j.1523-1755.62.s82.13.x.
Recently, the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Study demonstrated the benefit of losartan in reducing renal outcomes in patients with type 2 diabetes and proteinuria. Additional questions concerning the reduction of proteinuria and its relationship to end-stage renal disease (ESRD) as well as cardio-renal outcomes and the safety and tolerability of losartan remain to be addressed.
Three analyses were performed: (a) the impact of losartan on the relationship between the reduction of proteinuria and ESRD; (b) a time-to-event analysis of the cardio-renal composite endpoint of ESRD, myocardial infarction, stroke or all-cause death; and (c) additional analyses of adverse events, particularly in patients with serum creatinine >or=2.0 mg/dL.
After adjusting the values for proteinuria over the entire study, the reduction of proteinuria accounted for approximately half of the treatment effect of losartan on the risk reduction for ESRD. In addition, losartan was associated with a 21% risk reduction for the composite cardio-renal outcome (P=0.003). The addition of losartan to a conventional antihypertensive regimen did not increase the overall incidence of adverse events, regardless of severity of renal impairment.
Losartan significantly reduced the risk of cardiorenal outcomes and was well tolerated by patients, including those with serum creatinine levels >or=2.0 g/dL. In addition, although this study shows that the reduction of proteinuria does not completely explain the impact of intervention on outcomes such as ESRD, reduction of proteinuria must remain an important consideration when treating patients with type 2 diabetes and nephropathy. However, the reduction of outcomes such as ESRD should remain the goal of therapy when evaluating renal protection in this patient population.
最近，氯沙坦降低2型糖尿病肾病终点事件（RENAAL）研究证明了氯沙坦在降低2型糖尿病和蛋白尿患者肾脏终点事件方面的益处。关于蛋白尿降低及其与终末期肾病（ESRD）的关系、心肾终点事件以及氯沙坦的安全性和耐受性等其他问题仍有待解决。
进行了三项分析：（a）氯沙坦对蛋白尿降低与ESRD之间关系的影响；（b）对ESRD、心肌梗死、中风或全因死亡的心肾复合终点事件进行事件发生时间分析；（c）对不良事件进行额外分析，特别是血清肌酐≥2.0mg/dL的患者。
在对整个研究期间的蛋白尿值进行调整后，蛋白尿的降低约占氯沙坦降低ESRD风险治疗效果的一半。此外，氯沙坦使心肾复合终点事件风险降低了21%（P=0.003）。在传统降压方案中加用氯沙坦并未增加不良事件的总体发生率，无论肾功能损害的严重程度如何。
氯沙坦显著降低了心肾终点事件风险，患者耐受性良好，包括血清肌酐水平≥2.0mg/dL的患者。此外，尽管本研究表明蛋白尿的降低并不能完全解释干预对ESRD等结局的影响，但在治疗2型糖尿病和肾病患者时，蛋白尿的降低仍必须作为一个重要考虑因素。然而，在评估该患者群体的肾脏保护时，降低ESRD等结局仍应是治疗的目标。
