Paoli Sara, Mitsnefes Mark M
aDepartment of Pediatrics, University 'SAPIENZA', Pediatric Nephrology Policlinico Umberto I, Rome, Italy bDivision of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Curr Opin Pediatr. 2014 Apr;26(2):193-7. doi: 10.1097/MOP.0000000000000059.
Cardiovascular disease is the leading cause of death in children and young adults with end-stage renal disease (ESRD). As adults, children with advanced chronic kidney disease (CKD) have extremely high prevalence of traditional and uremia-related cardiovascular risk factors. Coronary artery calcification is one of the earliest cardiovascular markers detected in children with ESRD. The purpose of this review is to examine the new developments in pathogenesis of coronary artery calcification and to describe recently published studies on this topic in children with CKD.
There is growing evidence that fibroblast growth factor 23 (FGF23) and Klotho factor play a key role in the development of coronary artery calcification in ESRD. Recent studies have shown that induction of vascular calcification begins in early normophosphatemic CKD by the reduction of vascular Klotho and increased FGF23 secretion. Pediatric studies confirmed the presence of abnormal FGF23 and Klotho metabolism and the association of increased circulating FGF23 with coronary artery calcification in children with CKD.
New developments in our understanding of the mechanisms of vascular calcification in patients with early CKD require further investigation of whether control of FGF23/Klotho metabolism will prevent or delay the development of coronary artery calcification and other cardiovascular outcomes.
心血管疾病是终末期肾病（ESRD）患儿及年轻成人的主要死因。成年后，晚期慢性肾脏病（CKD）患儿传统及与尿毒症相关的心血管危险因素患病率极高。冠状动脉钙化是ESRD患儿最早检测到的心血管标志物之一。本综述旨在探讨冠状动脉钙化发病机制的新进展，并描述近期发表的关于CKD患儿这一主题的研究。
越来越多的证据表明，成纤维细胞生长因子23（FGF23）和Klotho因子在ESRD患者冠状动脉钙化的发生发展中起关键作用。近期研究表明，在早期血磷正常的CKD患者中，血管Klotho减少和FGF23分泌增加会引发血管钙化。儿科研究证实，CKD患儿存在FGF23和Klotho代谢异常，且循环FGF23升高与冠状动脉钙化有关。
我们对早期CKD患者血管钙化机制理解的新进展，需要进一步研究控制FGF23/Klotho代谢是否能预防或延缓冠状动脉钙化及其他心血管疾病的发生发展。
