From the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (I.O.S., A.S., A.A., A.E., C.M.F., J.R.W., S.C.T., A.S.P., L.O.L.).
Division of Nephrology, Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea (I.O.S.).
Hypertension. 2018 Nov;72(5):1180-1188. doi: 10.1161/HYPERTENSIONAHA.118.11766.
Hypertension, an important cause of chronic kidney disease, is characterized by peritubular capillary (PTC) loss. Circulating levels of endothelial microparticles (EMPs) reflect systemic endothelial injury. We hypothesized that systemic and urinary PTC-EMPs levels would reflect renal microvascular injury in hypertensive patients. We prospectively measured by flow cytometry renal vein, inferior vena cava, and urinary levels of EMPs in essential (n=14) and renovascular (RVH; n=24) hypertensive patients and compared them with peripheral blood and urinary levels in healthy volunteers (n=14). PTC-EMPs were identified as urinary exosomes positive for the PTC marker plasmalemmal-vesicle-associated protein. In 7 RVH patients, PTC and fibrosis were also quantified in renal biopsy, and in 18 RVH patients, PTC-EMPs were measured again 3 months after continued medical therapy with or without stenting (n=9 each). Renal vein and systemic PTC-EMPs levels were not different among the groups, whereas their urinary levels were elevated in both RVH and essential hypertension versus healthy volunteers (56.8%±12.7% and 62.8%±10.7% versus 34.0%±17.8%; both P≤0.001). Urinary PTC-EMPs levels correlated directly with blood pressure and inversely with estimated glomerular filtration rate. Furthermore, in RVH, urinary PTC-EMPs levels correlated directly with stenotic kidney hypoxia, histological PTC count, and fibrosis and inversely with cortical perfusion. Three months after treatment, the change in urinary PTC-EMPs levels correlated inversely with a change in renal function ( r=-0.582; P=0.011). Therefore, urinary PTC-EMPs levels are increased in hypertensive patients and may reflect renal microcirculation injury, whereas systemic PTC-EMPs levels are unchanged. Urinary PTC-EMPs may be useful as novel biomarkers of intrarenal capillary loss.
高血压是慢性肾脏病的一个重要病因,其特征是肾小管周毛细血管(PTC)丧失。循环内皮微颗粒(EMP)水平反映了全身内皮损伤。我们假设,系统性和尿 PTC-EMP 水平将反映高血压患者的肾微血管损伤。我们前瞻性地通过流式细胞术测量了 14 例原发性高血压(EH)和 24 例肾血管性高血压(RVH)患者的肾静脉、下腔静脉和尿中 EMP 水平,并将其与 14 名健康志愿者的外周血和尿中 EMP 水平进行了比较。PTC-EMP 被鉴定为尿外泌体,阳性标志物为 PTC 标记物质膜小泡相关蛋白。在 7 例 RVH 患者中,还对肾活检中的 PTC 和纤维化进行了定量,在 18 例 RVH 患者中,在继续药物治疗(或不进行支架置入)3 个月后再次测量了 PTC-EMP(n=9)。肾静脉和系统性 PTC-EMP 水平在各组之间没有差异,而它们的尿水平在 RVH 和 EH 中均高于健康志愿者(56.8%±12.7%和 62.8%±10.7%比 34.0%±17.8%;均 P≤0.001)。尿 PTC-EMP 水平与血压呈正相关,与估算肾小球滤过率呈负相关。此外,在 RVH 中,尿 PTC-EMP 水平与狭窄肾脏缺氧、组织学 PTC 计数、纤维化呈正相关,与皮质灌注呈负相关。治疗 3 个月后,尿 PTC-EMP 水平的变化与肾功能的变化呈负相关(r=-0.582;P=0.011)。因此,高血压患者的尿 PTC-EMP 水平升高,可能反映了肾微循环损伤,而系统性 PTC-EMP 水平不变。尿 PTC-EMP 可能是肾内毛细血管丢失的新型生物标志物。
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