Hospital of the University of Pennsylvania Philadelphia PA USA.
Bristol Myers Squibb Company Princeton NJ USA.
J Am Heart Assoc. 2024 Sep 3;13(17):e033660. doi: 10.1161/JAHA.123.033660. Epub 2024 Aug 29.
Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear.
Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort.
KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.
心力衰竭射血分数保留（HFpEF）患者常伴有肾脏疾病。然而，除估算肾小球滤过率（eGFR）外，HFpEF 患者肾脏损伤（KI）的生物学相关性及其预后意义尚不清楚。
我们利用 TOPCAT（醛固酮拮抗剂治疗保留射血分数的心力衰竭）试验的基线血浆样本，测定了以下 KI 生物标志物：胱抑素 C、脂肪酸结合蛋白-3、β2 微球蛋白、中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子 1。采用因子分析提取这些生物标志物的共同变异性。我们评估了 KI 因子评分与死亡或 HF 相关住院风险之间的关系，模型调整了 Meta-Analysis Global Group in Chronic Heart Failure 风险评分和 eGFR。我们还评估了 KI 因子评分与约 5000 种血浆蛋白之间的关系，然后进行途径分析。我们在 Penn Heart Failure Study 中的 HFpEF 参与者中验证了我们的发现。KI 与死亡或 HF 相关住院风险的相关性独立于 Meta-Analysis Global Group in Chronic Heart Failure 风险评分和 eGFR。在调整 KI 因子评分后，风险评分和 eGFR 与死亡或 HF 相关住院风险不再相关。KI 主要与补体激活、炎症、纤维化和胆固醇稳态相关的蛋白质和生物学途径相关。KI 与 140 种蛋白质相关，这些蛋白质在不同队列中均有重现。在验证队列中也重现了 KI 的生物学关联和预后意义的发现。
KI 与 HFpEF 不良结局相关，独立于基线 eGFR。伴有 KI 的 HFpEF 患者表现出补体激活、炎症、纤维化和胆固醇稳态受损的血浆蛋白质组学特征。
