Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada.
Diabetes Obes Metab. 2023 Aug;25(8):2331-2339. doi: 10.1111/dom.15112. Epub 2023 May 15.
In the CANVAS Program and CREDENCE trials, the sodium glucose co-transporter 2 inhibitor canagliflozin reduced the risk of cardiovascular and kidney events in patients with type 2 diabetes. The current study analysed a pooled population to ascertain the kidney protection provided by canagliflozin across the full spectrum of kidney parameters.
This post-hoc pooled analysis of the CANVAS Program (N = 10 142) and CREDENCE trial (N = 4401), assessed the risk of the primary kidney composite (doubling of serum creatinine, end-stage kidney disease, renal death), in all patients and subgroups defined by baseline estimated glomerular filtration rate (<30, 30 to <45, 45 to <60 and ≥60 ml/min/1.73 m ), albuminuria [<30, 30-300, >300 mg/g (<3.39, 3.39-33.9, >33.9 mg/mmol)] and 2012 Kidney Disease: Improving Global Outcomes (KDIGO) classification of chronic kidney disease (low/moderate, high and very high risk).
In the overall population, the risk for the primary kidney composite outcome was 37% lower in the canagliflozin group versus placebo (HR: 0.63; 95% CI: 0.53, 0.77; p < .001). There was no evidence of heterogeneity in the kidney protective effects of canagliflozin across a range of kidney risks when stratified by baseline estimated glomerular filtration rate, albuminuria or KDIGO risk category (all p > .05). A statistically significant risk reduction of the primary kidney composite outcome was sustained by approximately 18 months after randomization.
These results emphasize a critical role of canagliflozin in kidney protection across a broad spectrum of participants with type 2 diabetes with varying levels of kidney function.
在 CANVAS 项目和 CREDENCE 试验中，钠-葡萄糖协同转运蛋白 2 抑制剂卡格列净降低了 2 型糖尿病患者心血管和肾脏事件的风险。本研究分析了一个合并人群，以确定卡格列净在整个肾脏参数范围内提供的肾脏保护作用。
本研究是对 CANVAS 项目（N=10142）和 CREDENCE 试验（N=4401）的一项事后合并分析，评估了主要肾脏复合终点（血清肌酐加倍、终末期肾病、肾脏死亡）在所有患者和根据基线估计肾小球滤过率（<30、30 至<45、45 至<60 和≥60 ml/min/1.73 m ）、蛋白尿 [<30、30-300、>300 mg/g（<3.39、3.39-33.9、>33.9 mg/mmol）]和 2012 年肾脏病：改善全球结局（KDIGO）慢性肾脏病分类（低/中、高和极高风险）定义的亚组患者中的风险。
在总体人群中，卡格列净组的主要肾脏复合结局风险较安慰剂组降低 37%（HR：0.63；95%CI：0.53，0.77；p<0.001）。根据基线估计肾小球滤过率、蛋白尿或 KDIGO 风险类别分层，卡格列净对肾脏保护作用在一系列肾脏风险中无异质性（所有 p 值均>0.05）。在随机分组后约 18 个月，主要肾脏复合结局的风险降低仍具有统计学意义。
这些结果强调了卡格列净在 2 型糖尿病患者中广泛的肾脏保护作用，无论其肾功能水平如何，都具有重要作用。
