Heerspink H J L, Ninomiya T, Persson F, Brenner B M, Brunel P, Chaturvedi N, Desai A S, Haffner S M, Mcmurray J J V, Solomon S D, Pfeffer M A, Parving H-H, de Zeeuw D
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Division of Research Management, Center for Cohort Studies Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Diabetes Obes Metab. 2016 Feb;18(2):169-77. doi: 10.1111/dom.12600. Epub 2016 Jan 13.
To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria was too small to afford clinical benefit.
In a post hoc analysis of the ALTITUDE trial in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of albuminuria changes at 6 months on renal and cardiovascular outcomes using Cox proportional hazard regression.
The median change in albuminuria in the first 6 months in the aliskiren arm of the trial was -12% (25th to 75th percentile: -48.7_to_ +41.9%) and 0.0% (25th to 75th percentile: -40.2_to_55%) in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: a >30% reduction in albuminuria in the first 6 months was associated with a 62% reduction in renal risk and a 25% reduction in cardiovascular risk compared with an increase in albuminuria. The association between changes at 6 months in albuminuria and renal or cardiovascular endpoints was similar in the two treatment groups (p for interaction >0.1 for both endpoints).
The addition of aliskiren to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy resulted in albuminuria changes that were associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection because the overall reduction in albuminuria in the aliskiren arm was too small and nearly similar to that in the placebo arm.
研究在ALTITUDE试验中观察到的蛋白尿减少程度是否与肾脏和心血管保护相关，其次，蛋白尿减少幅度是否过小而无法带来临床益处。
在对8561例2型糖尿病合并慢性肾脏病或心血管疾病患者进行的ALTITUDE试验的事后分析中，我们使用Cox比例风险回归分析了6个月时蛋白尿变化对肾脏和心血管结局的影响。
试验中阿利吉仑组前6个月蛋白尿的中位数变化为-12%（第25至75百分位数：-48.7至+41.9%），安慰剂组为0.0%（第25至75百分位数：-40.2至55%）。前6个月蛋白尿的变化与肾脏和心血管终点呈线性相关：与蛋白尿增加相比，前6个月蛋白尿减少>30%与肾脏风险降低62%和心血管风险降低25%相关。两个治疗组中，6个月时蛋白尿变化与肾脏或心血管终点之间的关联相似（两个终点的交互作用p>0.1）。
在血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂治疗基础上加用阿利吉仑导致蛋白尿变化，这与肾脏和心血管风险变化相关。但这并未转化为肾脏或心血管保护，因为阿利吉仑组蛋白尿的总体减少幅度过小，且与安慰剂组几乎相似。
