Herrmann Sandra M S, Saad Ahmed, Eirin Alfonso, Woollard John, Tang Hui, McKusick Michael A, Misra Sanjay, Glockner James F, Lerman Lilach O, Textor Stephen C
Division of Nephrology and Hypertension and.
Department of Radiology, Mayo Clinic, Rochester, Minnesota.
Clin J Am Soc Nephrol. 2016 Mar 7;11(3):458-69. doi: 10.2215/CJN.03620415. Epub 2016 Jan 19.
Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured.
Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001).
These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines.
动脉粥样硬化性肾动脉狭窄（ARAS）可减少肾血流量、组织氧合及肾小球滤过率（GFR）。在本研究中，我们试图探讨接受单纯药物治疗或支架血管重建术的单侧ARAS患者的肾血流动力学和组织氧合与单肾肾功能、升压激素及炎症生物标志物之间的关联。
设计、地点、参与者及测量方法：对单侧ARAS（闭塞>60%）患者在血管重建术前及术后3个月（n = 10）或药物治疗后3个月（n = 20）进行非随机住院研究，或在相同条件下对原发性高血压患者（n = 32）进行研究。主要研究结局为单肾GFR的变化。使用多排螺旋CT测量单个肾脏的血流动力学和体积。通过3T的血氧水平依赖磁共振成像测定组织氧合（用R(2)*作为脱氧血红蛋白的指标）。测量肾静脉中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、单核细胞趋化蛋白-1（MCP-1）及血浆肾素活性。
两组患者在3个月内总GFR均未改变，但与药物治疗组相比，支架置入组狭窄肾（STK）的GFR随时间升高（+2.2[-1.8至10.5]对-5.3[-7.3至-0.3]ml/min；P = 0.03）。支架置入组对侧肾（CLK）的GFR下降（43.6±19.7至36.6±19.5ml/min；P = 0.03）。支架置入后STK的组织缺氧分数下降（R(2)*分数>30/s：22.1%±20%对14.9%±18.3%；P<0.01）。肾静脉生物标志物与STK的缺氧程度相关：NGAL（r = 0.3；P = 0.01）和MCP-1（r = 0.3；P = 0.02；支架置入后更明显）。肾静脉NGAL与STK的肾血流量呈负相关（r = -0.65；P<0.001）。STK与CLK之间的生物标志物高度相关，NGAL（r = 0.94；P<0.001）和MCP-1（r = 0.96；P<0.001）。
这些结果显示单肾GFR随时间发生变化，而总GFR参数中未明显体现。此外，它们描绘了STK内可测量的组织缺氧与人类ARAS炎症标志物之间的关系。肾静脉NGAL和MCP-1表明缺血肾与CLK及全身炎症细胞因子水平之间存在持续相互作用。
