Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Division of Cardiology, Rush University Medical Center, Chicago, IL, USA.
J Investig Med. 2024 Oct;72(7):640-651. doi: 10.1177/10815589241249991. Epub 2024 May 22.
Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of estimated glomerular filtration rate (eGFR) in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants, mean age was 59 years, median eGFR 60 ml/min/1.73 m, 45 participants died, 33 received VAD, and 25 received orthotopic heart transplantation. Higher baseline serum standardized suPAR (β coefficient = -0.36 √(ml/min/1.73 m), 95% confidence interval (-0.48 to -0.24), p < 0.001), standardized galectin-3 (-0.14 √(ml/min/1.73 m) (-0.27 to -0.02), p = 0.02), and log NT-proBNP (-0.23 √(ml/min/1.73 m) (-0.31 to -0.15), p < 0.001) were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.
患有射血分数降低的心力衰竭（HFrEF）的患者有发生慢性肾脏病（CKD）的风险。循环生物标志物可溶性尿激酶型纤溶酶原激活物受体（suPAR）、半乳糖凝集素-3、可溶性抑制肿瘤生成 2（ST2）和 N 端脑钠肽前体（NT-proBNP）水平升高与 CKD 进展和死亡率相关。这些生物标志物在 HFrEF 合并肾脏疾病患者中的预测价值相对未知。我们旨在确定这些生物标志物是否与 HFrEF 患者肾小球滤过率（eGFR）的纵向轨迹相关，并使用联合模型评估它们与死亡率的相关性，该模型考虑到心室辅助装置（VAD）植入和心脏移植的竞争风险。我们纳入了在 2 年时间内重复进行 eGFR 测量的注册评估生命重要信息的心室辅助装置门诊生活参与者。在 309 名参与者中，平均年龄为 59 岁，中位 eGFR 为 60ml/min/1.73m，45 人死亡，33 人接受 VAD，25 人接受原位心脏移植。基线血清标准化 suPAR（β系数= -0.36√(ml/min/1.73m)，95%置信区间（-0.48 至 -0.24），p<0.001）、标准化半乳糖凝集素-3（-0.14√(ml/min/1.73m)，（-0.27 至 -0.02），p=0.02）和 log NT-proBNP（-0.23√(ml/min/1.73m)，（-0.31 至 -0.15），p<0.001）与 eGFR 下降相关。ST2 和 log NT-proBNP 与死亡率相关。基线 suPAR、半乳糖凝集素-3 和 NT-proBNP 较高与 HFrEF 患者的 eGFR 下降相关。仅 ST2 和 NT-proBNP 与其他因素（包括 eGFR 变化）控制后更大的死亡率相关。这些生物标志物可能为 HFrEF 患者的肾脏疾病进展提供预后价值，并为晚期心力衰竭治疗的候选资格提供信息。
