Bolignano Davide, Greco Marta, Arcidiacono Valentina, Presta Pierangela, Caglioti Alfredo, Russo Emilio, Andreucci Michele, Tripolino Omar, Carullo Nazareno, Foti Daniela Patrizia, Coppolino Giuseppe
Renal Unit, "Magna Graecia'' University, 88100 Catanzaro, Italy.
Clinical Pathology Lab, "Magna Graecia'' University, 88100 Catanzaro, Italy.
Rev Cardiovasc Med. 2022 Sep 13;23(9):311. doi: 10.31083/j.rcm2309311. eCollection 2022 Sep.
In kidney transplantation (Ktx) recipients, cardiovascular (CV) disease remains the leading cause of death. Abnormal carotid intima-media thickness (IMT) represents a valid indicator of incipient atherosclerosis also in this setting. Cathepsin-K (CatK) is a cysteine protease involved in vascular remodelling, as well as in progressive atherosclerosis. In this study we evaluated clinical predictors of CatK in Ktx recipients, with a particular focus on its possible relationships with subclinical atherosclerosis.
Circulating CatK was measured in 40 stable Ktx recipients together with several laboratory, clinical and echocardiography parameters. 30 healthy subjects and 30 hemodialysis (HD) patients served as controls for CatK values. Carotid IMT was measured in Ktx and these subjects were then categorized according to age-gender reference cut-offs of normal IMT.
CatK levels were similar in Ktx recipients and healthy subjects but significantly reduced as compared to HD ( = 0.0001). In Ktx, at multivariate analyses CatK was associated with the LV end-diastolic volume (LVEDVi) ( = 0.514; = 0.05), Ktx vintage ( = -0.333; = 0.05) and mean IMT ( = -0.545; = 0.05); this latter robust inverse association was confirmed also in another multivariate model with IMT as the dependent variable. Logistic regression analyses confirmed the beneficial meaning of CatK increase towards subclinical atherosclerosis [Odds Ratio (OR) 0.761; 95% Confidence Interval (CI) 0.569-0.918, = 0.04]. At Receiver Operating Characteristics (ROC) analyses, CatK held a remarkable discriminatory power in identifying Ktx patients with abnormally increased IMT [Area Under the Curve (AUC) 0.763; 95% CI 0.601-0.926; = 0.001]).
In Ktx recipients, reduced CatK levels reflect the time-dependent improvement in the uremic milieu, cardiac adaptations and, above all, the severity of subclinical atherosclerosis. CatK measurement in Ktx may therefore hold significance for improving early CV risk stratification.
在肾移植（Ktx）受者中，心血管（CV）疾病仍然是主要死因。颈动脉内膜中层厚度（IMT）异常在此情况下也是早期动脉粥样硬化的有效指标。组织蛋白酶K（CatK）是一种参与血管重塑以及进行性动脉粥样硬化的半胱氨酸蛋白酶。在本研究中，我们评估了Ktx受者中CatK的临床预测因素，特别关注其与亚临床动脉粥样硬化的可能关系。
对40名稳定的Ktx受者以及多项实验室、临床和超声心动图参数进行循环CatK检测。30名健康受试者和30名血液透析（HD）患者作为CatK值的对照。对Ktx受者测量颈动脉IMT，然后根据正常IMT的年龄-性别参考临界值对这些受试者进行分类。
Ktx受者和健康受试者的CatK水平相似，但与HD相比显著降低（P = 0.0001）。在Ktx受者中，多变量分析显示CatK与左心室舒张末期容积（LVEDVi）相关（P = 0.514；P = 0.05）、肾移植时间（P = -0.333；P = 0.05）和平均IMT相关（P = -0.545；P = 0.05）；在另一个以IMT为因变量的多变量模型中也证实了这种强烈的负相关。逻辑回归分析证实了CatK升高对亚临床动脉粥样硬化的有益意义[比值比（OR）0.761；95%置信区间（CI）0.569 - 0.918，P = 0.04]。在受试者工作特征（ROC）分析中，CatK在识别IMT异常升高的Ktx患者方面具有显著的鉴别能力[曲线下面积（AUC）0.763；95% CI 0.601 - 0.926；P = 0.001]。
在Ktx受者中，CatK水平降低反映了尿毒症环境、心脏适应性随时间的改善，最重要的是反映了亚临床动脉粥样硬化的严重程度。因此，在Ktx受者中测量CatK可能对改善早期心血管风险分层具有重要意义。
