Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 86, Stockholm, Sweden.
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
Biol Sex Differ. 2023 Jul 13;14(1):48. doi: 10.1186/s13293-023-00530-x.
Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF.
KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables.
Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p < 0.001). Age-adjusted analyses revealed that in males CAC was associated with diabetes mellitus (DM) (p = 0.018) and CVD (p = 0.011). Additionally, for females CAC associated with IL-6 (p = 0.005) and TNF (p = 0.004). In both females and males CAC associated with AGE (p = 0.042 and p = 0.05, respectively). CAC was associated with mortality for females (p = 0.015) independent of age. AVC in females was not reviewed due to low AVC-positive samples (n = 14). In males, in multivariable regression AVC was associated with age (p < 0.001) and inflammation, as measured by IL-6 (p = 0.010).
In female KF patients inflammatory burden and oxidative stress were associated with CAC. Whereas in male KF patients oxidative stress and inflammation were associated with CAC and AVC, respectively. Our findings suggest a sex-specific biomarker signature for cardiovascular calcification that may affect the development of cardiovascular complications in males and females with KF.
慢性肾脏病（CKD）与心血管疾病（CVD）负担增加有关。尽管认识不足，但CKD 中存在明显的性别差异，女性更容易发生 CKD，但男性更快进展为肾衰竭（KF）。心血管重塑是 CKD 的标志，动脉和瓣膜钙化增加导致 CKD。然而，关于 KF 患者钙化性心血管重塑的性别差异知之甚少。因此，我们假设 KF 患者的冠状动脉钙化（CAC）和主动脉瓣钙化（AVC）存在性别差异。
从三个 CKD 队列中选择了接受计算机断层扫描（CT）评估 CAC 和 AVC 的 KF 男性患者（n=214）和女性患者（n=107）。所有患者均接受非对比多探测器心脏 CT 扫描，CAC 和 AVC 评分基于 Agatston 方法。从队列数据库中检索了基线生化测量值，包括炎症标志物（IL-6、TNF、hsCRP）和通过皮肤自发荧光测量氧化应激的高级糖基化终产物（AGE）等变量的血浆分析。
性别细分分析显示，CAC 评分与男性和女性的年龄相关（均 p<0.001）。年龄调整分析显示，在男性中，CAC 与糖尿病（DM）（p=0.018）和 CVD（p=0.011）相关。此外，对于女性，CAC 与 IL-6（p=0.005）和 TNF（p=0.004）相关。在女性和男性中，CAC 与 AGE 相关（p=0.042 和 p=0.05）。CAC 与女性的死亡率相关（p=0.015），与年龄无关。由于 AVC 阳性样本较少（n=14），未对女性的 AVC 进行评估。在男性中，多变量回归显示 AVC 与年龄（p<0.001）和炎症标志物 IL-6 相关（p=0.010）。
在女性 KF 患者中，炎症负担和氧化应激与 CAC 相关。而在男性 KF 患者中，氧化应激和炎症分别与 CAC 和 AVC 相关。我们的发现表明，心血管钙化存在性别特异性的生物标志物特征，可能影响男性和女性 KF 患者心血管并发症的发展。
