Wang Wei, Saad Ahmed, Herrmann Sandra M, Eirin Massat Alfonso, McKusick Michael A, Misra Sanjay, Lerman Lilach O, Textor Stephen C
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA Department of Nephrology, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, Liaoning, China.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Nephrol Dial Transplant. 2016 Sep;31(9):1437-43. doi: 10.1093/ndt/gfv448. Epub 2016 Jan 29.
Atherosclerotic renal artery stenosis (ARAS) activates oxidative stress and chronic inflammatory injury. Contrast imaging and endovascular stenting pose potential hazards for acute kidney injury, particularly when superimposed upon reduced kidney perfusion.
We measured sequential early and long-term changes in circulating inflammatory and injury biomarkers in 12 ARAS subjects subjected to computed tomography imaging and stent revascularization compared with essential hypertensive (EH) subjects of similar age under fixed sodium intake and medication regimens in a clinical research unit.
NGAL, TIMP-2, IGFBP7, MCP-1 and TNF-α all were elevated before intervention. Post-stenotic kidney volume, perfusion, blood flow and glomerular filtration rate (GFR) were lower in ARAS than in EH subjects. TIMP-2 and IGFBP7 fell briefly, then rose over 18 h after contrast imaging and stent deployment. Circulating NGAL decreased and remained lower for 27 h. These biomarkers in ARAS returned to baseline after 3 months, while kidney volume, perfusion, blood flow and GFR increased, but remained lower than EH.
These divergent patterns of inflammatory signals are consistent with cell cycle arrest (TIMP-2, IGFBP7) and relative protection from acute kidney injury after imaging and stenting. Sustained basal elevation of circulating and renal venous inflammatory biomarkers support ongoing, possibly episodic, renal stress in ARAS that limits toxicity from stent revascularization.
动脉粥样硬化性肾动脉狭窄（ARAS）会激活氧化应激和慢性炎症损伤。对比成像和血管内支架置入对急性肾损伤存在潜在风险，尤其是在肾灌注减少的情况下。
在临床研究单位中，我们测量了12例接受计算机断层扫描成像和支架血管重建术的ARAS患者以及年龄相仿的原发性高血压（EH）患者在固定钠摄入和药物治疗方案下循环炎症和损伤生物标志物的早期和长期连续变化。
干预前，中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、基质金属蛋白酶组织抑制因子-2（TIMP-2）、胰岛素样生长因子结合蛋白7（IGFBP7）、单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子-α（TNF-α）均升高。ARAS患者狭窄后肾脏体积、灌注、血流量和肾小球滤过率（GFR）低于EH患者。对比成像和支架置入后，TIMP-2和IGFBP7短暂下降，然后在18小时内上升。循环中的NGAL下降并在27小时内保持较低水平。3个月后，ARAS患者的这些生物标志物恢复至基线水平，而肾脏体积、灌注、血流量和GFR增加，但仍低于EH患者。
这些不同的炎症信号模式与细胞周期停滞（TIMP-2、IGFBP7）以及成像和支架置入后对急性肾损伤的相对保护作用一致。循环和肾静脉炎症生物标志物的持续基础升高支持ARAS中持续存在的、可能是间歇性的肾应激，这限制了支架血管重建术的毒性。
