Faguer Stanislas, Piedrafita Alexis, Sanz Ana Belen, Siwy Justyna, Mina Ioanna K, Alves Melinda, Bousquet Paul, Marcheix Bertrand, Casemayou Audrey, Klein Julie, Minville Vincent, Breuil Benjamin, Ortiz Alberto, Schanstra Joost P
Department of Nephrology and Organ Transplantation, French Intensive Care Renal Network, University Hospital of Toulouse, Toulouse, France.
National Institute of Health and Medical Research, UMR 1297 (Institute of Metabolic and Cardiovascular Diseases), Toulouse, France.
Clin Kidney J. 2024 Mar 27;17(5):sfae091. doi: 10.1093/ckj/sfae091. eCollection 2024 May.
Before implementing individualized strategies to treat acute kidney injury (AKI), identifying clusters of patients with divergent pathophysiological mechanisms, diagnosis criteria or outcomes is of the utmost importance. Here we studied sex-related molecular mechanisms in cardiac bypass (CBP) surgery patients developing AKI.
We compared the characteristics of 1170 patients referred for CBP surgery using multivariate logistic regression and propensity score-based analysis. Performances of the candidate urinary biomarkers at <4 h post-surgery, urinary neutrophil gelatinase-associated lipocalin (uNGAL), [IGFBP7]·[TIMP-2] product (NephroCheck) and a recently developed AKI signature of 204 urinary peptides (AKI204) to predict AKI were compared in both sexes.
Incidence (∼25%) and severity of AKI were similar in men and women, even after adjustment for the usual risk factors of AKI, including baseline estimated glomerular filtration rate, age, diabetes mellitus, length of CBP and red blood cell transfusion. However, at the molecular level, performances of uNGAL, NephroCheck and AKI204 to predict AKI strongly diverged between men and women. In the full cohort, as well as in subgroups of men and women, the multimarker AKI204 signature outperformed uNGAL and NephroCheck and predicted the development of AKI significantly better in women than in men. Analysis of AKI204 at the single-peptide level suggested divergences of AKI mechanisms between sexes due to increased kidney inflammation in women (increased abundance of urinary fragments of osteopontin and uromodulin).
In patients referred for CBP surgery, significant clinical and biological differences between men and women as well as sexual dimorphism of AKI biomarker performances were identified. The urinary peptide signature points to sex-related molecular mechanisms underlying AKI.
在实施个体化策略治疗急性肾损伤（AKI）之前，识别具有不同病理生理机制、诊断标准或预后的患者群体至关重要。在此，我们研究了心脏搭桥（CBP）手术患者发生AKI的性别相关分子机制。
我们使用多因素逻辑回归和基于倾向评分的分析方法，比较了1170例接受CBP手术患者的特征。比较了术后<4小时时候选尿生物标志物、尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）、[胰岛素样生长因子结合蛋白7]·[基质金属蛋白酶组织抑制因子-2]产物（NephroCheck）以及最近开发的204种尿肽的AKI特征（AKI204）在预测男女AKI方面的性能。
即使在对AKI的常见危险因素进行调整后，包括基线估计肾小球滤过率、年龄、糖尿病、CBP时长和红细胞输注，男性和女性的AKI发病率（约25%）和严重程度相似。然而，在分子水平上，uNGAL、NephroCheck和AKI204在预测AKI方面的性能在男性和女性之间存在显著差异。在整个队列以及男性和女性亚组中，多标志物AKI204特征优于uNGAL和NephroCheck，并且在预测女性AKI发生方面显著优于男性。在单肽水平对AKI204的分析表明，由于女性肾脏炎症增加（骨桥蛋白和尿调节蛋白的尿片段丰度增加），两性之间AKI机制存在差异。
在接受CBP手术的患者中，发现了男性和女性之间显著的临床和生物学差异以及AKI生物标志物性能的性别二态性。尿肽特征指出了AKI潜在的性别相关分子机制。
