首页> 外文期刊>American Journal of Physiology >Albuminuria in kidney transplant recipients is associated with increased urinary serine proteases and activation of the epithelial sodium channel
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Albuminuria in kidney transplant recipients is associated with increased urinary serine proteases and activation of the epithelial sodium channel

机译:肾移植受者的白蛋白尿与增加的尿液丝氨酸蛋白酶和上皮钠通道的激活有关

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Albuminuria predicts adverse renal outcome in kidney transplant recipients. The present study addressed the hypothesis that albuminuria is associated with increased urine serine proteases with the ability to activate the epithelial sodium channel (ENaC) and with greater extracellular volume and higher blood pressure. In a cross-sectional design, kidney transplant recipients with (n = 18) and without (n = 19) albuminuria were included tor office blood pressure measurements, estimation of volume status by bioimpedance, and collection of spot urine and plasma samples. Urine was analyzed for serine proteases and for the ability to activate ENaC current in vitro. Urine exosome protein was imnumoblotted for prostasin and 7-ENaC protein. In the present study, it was found that, compared with nonalbuminuria (8.8 mg/g creatinine), albuminuric (1,722 mg/g creatinine) kidney transplant recipients had a higher systolic and diastolic blood pressure, despite receiving significantly more antihypertensives, and a greater urinary total plasminogen, active plasmin, active urokinase-type plasminogen activator, and prostasin protein abundance, which correlated significantly with u-al-bumin. Fluid overload correlated with systolic blood pressure, urinary albumin/creatinine, and plasminogen/creatinine. Urine from albumin-uric kidney transplant recipients evoked a greater amiloride- and aprotinin-sensitive inward current in single collecting duct cells (mu-rine cell line Ml). γENaC subunits at 50 and 75 kDa showed increased abundance in urine exosomes from albuminuric kidney transplant recipients when compared with controls. These findings show that albuminuria in kidney transplant recipients is associated with hypertension, ability of urine to proleolytically activate ENaC current, and increased abundance of 7ENaC. ENaC activity could contribute to hypertension and adverse outcome in posttransplant proteinuria.
机译:白蛋白尿预测肾移植受者的不良肾果糖。本研究涉及具有尿液丝氨酸蛋白酶增加的假设,具有激活上皮钠通道(ENAC)和更高的细胞外体积和更高血压的能力。在横截面设计中,肾移植受者(N = 18)和没有(n = 19)白蛋白尿,包括托特办公室血压测量,通过生物阻抗估计体积状态,以及集合尿液和血浆样品的收集。针对丝氨酸蛋白酶分析尿液,并能够在体外激活enac电流的能力。尿液外蛋白是用于前列腺蛋白和7-enac蛋白的蛋白质。结果发现,与壬会(8.8mg / g肌酐)相比,白蛋白(1,722mg / g肌酐)肾移植受者仍具有更高的收缩性和舒张血压,尽管抗高血压性显着增加,更大尿总纤溶酶原,活性纤溶酶,活性尿激酶型纤溶酶原激活剂和前列腺蛋白蛋白质丰富,其与U-Al-Bumin显着相关。流体过载与收缩压,尿白蛋白/肌酐和纤溶酶原/肌酐相关。来自白蛋白-uric肾移植受体的尿液引发了单收集管道细胞(MU- rine细胞系M1)中的更大的仲酰胺和抑肽酶敏感的内向电流。与对照相比,50和75kDa在50和75kDa处的γEnac亚基在尿液肾移植受者中显示出尿液外泌尿量增加。这些研究结果表明,肾移植受者的白蛋白尿与高血压有关,尿液能力对验证性激活enac电流,以及增加的7enac丰富。 ENAC活性可能有助于普及蛋白蛋仔尿的高血压和不良结果。

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