Department of Nephrology, Doncaster and Bassetlaw Teaching Hospitals, Doncaster DN2 5LT, UK.
Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9DA, UK.
Toxins (Basel). 2018 Dec 5;10(12):520. doi: 10.3390/toxins10120520.
Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2⁻5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPO), aerobic exercise capacity (VO), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPO and VO. IXS and PCS were independently associated with CPO and VO even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins.
尽管过去已经研究了蛋白质结合尿毒症毒素（PBUT）与慢性肾脏病（CKD）中心脏结构和心脏死亡率之间的关系，但 PBUT 与心脏功能障碍之间的关联尚未得到研究。因此，我们评估了心脏功能障碍与潜在的心脏毒性 PBUT 血清游离和总浓度之间的关系。在一项横断面研究中，我们评估了 56 名男性 CKD 患者（2⁻5 期（透析前））的峰值心脏性能受损与血清游离和总浓度之间的关系，这些患者无症状，无已知的心脏疾病或糖尿病，我们测量了峰值心脏功率（CPO）、有氧运动能力（VO）和心脏形态学的超声心动图参数，并评估了它们与 PBUT 的相关性。硫酸吲哚酚（IXS）、对甲酚硫酸盐（PCS）、对甲酚葡萄糖醛酸、吲哚乙酸和马尿酸的血清总浓度和游离浓度与 CPO 和 VO 呈显著负相关。即使在控制 eGFR 后，IXS 和 PCS 仍与 CPO 和 VO 独立相关。左心室质量指数（LVMI）与 PBUT 之间没有相关性。本研究首次证明了 CKD 亚临床心脏功能障碍与一组 PBUT 血清水平之间的关系。需要进一步研究评估个体尿毒症毒素的心脏毒性机制。
