Centre D'Investigation Clinique-Plurithématique Inserm CIC-P 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Institut Lorrain Du Coeur et des Vaisseaux Louis Mathieu, Vandoeuvre lès Nancy, France.
Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal.
Am J Nephrol. 2021;52(12):969-976. doi: 10.1159/000519436. Epub 2021 Dec 6.
Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important.
Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction.
WKF was defined as a ≥40% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR <15 mL/min, or dialysis. Mixed-effects and time-updated Cox models were used.
5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a p value ≤0.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06-7.96), p value <0.0001.
Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality.
2 型糖尿病（T2D）合并近期急性冠状动脉综合征（ACS）患者常出现肾功能恶化（WKF），且预后不良。准确预测 WKF 具有重要的临床意义。
利用 Alogliptin 在 2 型糖尿病和急性冠状动脉综合征患者心血管结局研究中的数据，该研究纳入了 T2D 合并近期 ACS 的患者，并结合包含血液和尿液中测量的蛋白质的大型生物标志物组，我们旨在确定那些对 WKF 预测具有最佳性能的标志物。
WKF 定义为肾小球滤过率（eGFR）从基线下降≥40%，eGFR<15 mL/min 或需要透析。采用混合效应和时间更新的 Cox 模型。
共纳入 5131 例患者，其中 222 例（4.3%）在中位随访 18 个月期间至少发生了一次 WKF 事件。发生 WKF 的患者更常见于女性，糖尿病病程更长，心力衰竭史更频繁，贫血发生率更高，肾功能受损。在包括所有与 WKF 相关的变量（临床和生物标志物）的多变量模型中，具有最强 WKF 相关性的变量是血肾损伤分子 1（KIM-1）（到目前为止），其次是贫血。仅 KIM-1 对 WKF 预测具有良好的区分能力（曲线下面积=0.73）。在高 KIM-1 衍生风险三分位的患者发生任何 WKF 的风险是低风险患者的 6.7 倍。在时间更新的 Cox 模型中，WKF 的发生与更高的死亡风险独立相关：调整后的危险比=4.93（3.06-7.96），p 值<0.0001。
血 KIM-1 是与 WKF 关联最强的生物标志物。WKF 的发生与随后发生心血管事件和死亡的风险增加独立相关。
