Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy:: Post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial
Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy:: Post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial
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DOI：
10.1681/asn.2006050445
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发表时间：
2007-05-01
影响因子：
13.6
通讯作者：
de Zeeuw, Dick
中科院分区：
文献类型：
--
作者：
Eijkelkamp, Wouter B. A.;Zhang, Zhongxin;de Zeeuw, Dick
减少蛋白尿对高血压合并糖尿病肾病患者具有肾脏保护作用。然而，目前使用的肾素-血管紧张素系统干预仅针对BP。因此，本研究在1428例高血压和糖尿病肾病患者中调查了这种方法的充分性，这些患者来自安慰剂对照的血管紧张素II拮抗剂氯沙坦（RENAAL）降低NIDDM终点的研究。在多变量考克斯模型中研究了治疗对收缩压（SBP）和蛋白尿影响的不一致程度及其与肾脏结局的相关性。在治疗期间SBP降低的患者中，在第6个月时，分别有37%、26%和51%的患者（总患者、氯沙坦患者和安慰剂患者）的白蛋白尿没有减少。SBP或白蛋白尿减少与ESRD风险降低相关，而SBP和白蛋白尿联合减少与事件风险最低相关。在所有SBP变化类别中，观察到ESRD风险比逐渐降低，白蛋白尿减少幅度较大。残余蛋白尿水平较低也与ESRD风险较低相关。总之，当滴定血压时，大部分患者的白蛋白尿变化并不一致。同时，终末期肾病的风险表现出明显的依赖于蛋白尿减少。ESRD风险还显示依赖于蛋白尿的残留水平，即使在达到当前SBP目标的患者中。因此，旨在改善糖尿病肾病患者肾脏结局的抗高血压治疗可能需要双重策略，以降低SBP和白蛋白尿为目标。
Albuminuria reduction could be renoprotective in hypertensive patients with diabetic nephropathy. However, the current use of renin-angiotensin-system intervention is targeted to BP only. Therefore, this study investigated the adequacy of this approach in 1428 patients with hypertension and diabetic nephropathy from the placebo-controlled Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. investigated were the extent of discordance in treatment effects on systolic BP (SBP) and albuminuria and its association with renal outcome in a multivariate Cox model. Among patients with a reduced SBP during treatment, a lack of albuminuria reduction was observed in 37,26, and 51% (total, losartan, and placebo, respectively) at month 6. SBP or albuminuria reduction was associated with a lower risk for ESRD, whereas combined SBP and albuminuria reduction was associated with the lowest risk for events. Across all categories of SBP change, a progressively lower ESRD hazard ratio was observed with a larger albuminuria reduction. A lower residual level of albuminuria was also associated with lower ESRD risk. In conclusion, changes in albuminuria are not concordant in a substantial proportion of patients when titrated for BP. Meanwhile, the ESRD risk showed a clear dependence on albuminuria reduction. The ESRD risk also showed dependence on the residual level of albuminuria, even in patients who reached the current SBP target. Antihypertensive treatment that is aimed at improving renal outcomes in patients with diabetic nephropathy may therefore require a dual strategy, targeting both SBP and albuminuria reduction.