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[高血压患者肾脏中蛋白水解/纤维蛋白溶解及纤维血管生成的尿标志物测定]

[Determination of urinary markers of proteolysis/fibrinolysis and fibroangiogenesis in the kidney in hypertensive patients].

作者信息

Nanchikeeva M L, Kozlovskaia L V, Rameev V V, Fomin V V, Bulanov N M

出版信息

Ter Arkh. 2011;83(6):23-7.

Abstract

AIM

To determine clinical significance of urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in essential hypertension (EH).

MATERIAL AND METHODS

Examination of the kidneys was made in 71 patients with EH degree 1-3. Renal function was assessed by 24-h albuminuria, calculated glomerular filtration rate (GFR) by Cockroft-Golt. Early signs of renal damage were microalbuminuria--MAU (diurnal albuminuria 30-300 mg/day), reduction of GFR (< 90 ml/min/1.73 m2). EH patients with hypercreatininemia and GFR under 60 ml/min/1.73m2 corresponding to stage III of chronic kidney disease were not included in the study. An additional nephropathy marker was an elevated index of resistance of interlobular renal arteries (RI > 0.65) as shown by dopplerometry. ELISA examined urinary biomarkers of intercellular and cell-matrix interactions in the kidney in EHpatients and healthy controls (n = 12).

RESULTS

MAU was detected in 54 (76%) of 71 EH patients, elevated RI > 0.65--in 37 (52%) patients. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis were higher in EH patients then in the controls. Urinary excretion of PAI-1, TGF-beta1, VEGF and collagen of type IV in EH patients with MAU was significantly higher than in patients with normoalbuminuria. A strong direct correlation between MAU and the rest above urinary biomarkers was found as well as between urinary excretion of collagen IV and RI. An inverse negative relationship was seen between RI and GFR.

CONCLUSION

Renal impairment in EHpatients is a progressive disorder. Each stage of this process has its own clinicodiagnostic markers. Urinary biomarkers ofproteolysis/fibrinolysis and fibroangiogenesis in the kidney are informative for monitoring of early HNP.

摘要

目的

确定蛋白水解/纤维蛋白溶解及纤维血管生成的尿生物标志物在原发性高血压(EH)中的临床意义。

材料与方法

对71例1 - 3级EH患者进行肾脏检查。通过24小时蛋白尿评估肾功能,采用Cockroft - Golt公式计算肾小球滤过率(GFR)。肾脏损害的早期迹象为微量白蛋白尿——MAU(日间蛋白尿30 - 300毫克/天),GFR降低(<90毫升/分钟/1.73平方米)。血肌酐升高且GFR低于60毫升/分钟/1.73平方米(对应慢性肾脏病Ⅲ期)的EH患者未纳入本研究。另一个肾病标志物是通过多普勒超声显示的肾小叶间动脉阻力指数升高(RI>0.65)。采用酶联免疫吸附测定法(ELISA)检测EH患者和健康对照者(n = 12)尿液中肾脏细胞间和细胞 - 基质相互作用的生物标志物。

结果

71例EH患者中有54例(76%)检测到MAU,37例(52%)患者RI升高>0.65。EH患者尿液中蛋白水解/纤维蛋白溶解及纤维血管生成的生物标志物高于对照组。MAU的EH患者尿液中纤溶酶原激活物抑制剂 - 1(PAI - 1)、转化生长因子 - β1(TGF - β1)、血管内皮生长因子(VEGF)和Ⅳ型胶原蛋白的排泄量显著高于正常白蛋白尿患者。MAU与上述其余尿液生物标志物之间以及Ⅳ型胶原蛋白尿排泄量与RI之间均存在强正相关。RI与GFR之间呈负相关。

结论

EH患者的肾脏损害是一种进行性疾病。该过程的每个阶段都有其自身的临床诊断标志物。肾脏中蛋白水解/纤维蛋白溶解及纤维血管生成的尿生物标志物对早期高血压肾病的监测具有指导意义。

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