IIS-Fundacion Jimenez Diaz/UAM/FRIAT, Madrid, Spain.
Int Urol Nephrol. 2012 Dec;44(6):1731-44. doi: 10.1007/s11255-012-0271-4. Epub 2012 Sep 11.
End-stage renal disease patients suffer a syndrome of accelerated aging characterized by a 10- to 100-fold increase in cardiovascular and all-cause mortality when compared to age-matched controls. No specific therapeutic interventions have been shown to improve this dismal outcome. Inflammation, chronic kidney disease-mineral and bone disorder (CKD-MBD) and other biomarkers predict outcome in observational studies. However, we lack clinical trials that address the role of these biomarkers in risk stratification and therapeutic decision making. Biomarkers may also provide insights into the pathophysiology of disease and identify novel therapeutic targets. Inflammation emerges as a prime potential target for intervention. Thus, CKD-MBD biomarkers, asymmetrical dimethyl arginine and tri-iodothyronine have a link to inflammation. Interleukin-6 (IL-6) is one of the inflammation biomarkers with highest predictive value for outcome in ESRD. Biologicals targeting IL-6 are approved for the treatment of chronic inflammatory conditions such as rheumatoid arthritis. Furthermore, trials are underway to test IL-6 targeting potential to decrease cardiovascular injury in non-CKD patients. In this regard, targeting IL-1 was recently shown to decrease systemic inflammation in hemodialysis patients. The success of these trials will likely influence future studies on biomarker targeting in CKD.
终末期肾病患者患有加速衰老综合征,与年龄匹配的对照组相比,其心血管疾病和全因死亡率增加了 10 至 100 倍。目前还没有特定的治疗干预措施被证明可以改善这种糟糕的结局。炎症、慢性肾脏病-矿物质和骨异常(CKD-MBD)和其他生物标志物在观察性研究中预测结局。然而,我们缺乏临床试验来解决这些生物标志物在风险分层和治疗决策中的作用。生物标志物还可以深入了解疾病的病理生理学,并确定新的治疗靶点。炎症成为一个潜在的干预目标。因此,CKD-MBD 生物标志物、非对称二甲基精氨酸和三碘甲状腺原氨酸与炎症有关。白细胞介素 6(IL-6)是 ESRD 中对结局预测价值最高的炎症生物标志物之一。针对 IL-6 的生物制剂已被批准用于治疗类风湿关节炎等慢性炎症性疾病。此外,正在进行临床试验以测试 IL-6 靶向治疗潜力,以减少非 CKD 患者的心血管损伤。在这方面,最近的研究表明靶向 IL-1 可以减少血液透析患者的全身炎症。这些试验的成功很可能会影响未来 CKD 中针对生物标志物的研究。