Cottone Santina, Mulè Giuseppe, Guarneri Marco, Palermo Alessandro, Lorito Maria C, Riccobene Raffaella, Arsena Rosalia, Vaccaro Francesco, Vadalà Anna, Nardi Emilio, Cusimano Paola, Cerasola Giovanni
Cattedra di Nefrologia e U.O. di Malattie Renali ed Ipertensione Arteriosa, Italy.
Nephrol Dial Transplant. 2009 Feb;24(2):497-503. doi: 10.1093/ndt/gfn489. Epub 2008 Sep 4.
Hypertension and additional non-traditional risk factors can damage the kidney directly and by promoting atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate a large part of the effects of risk factors on the kidney. We hypothesized that in hypertensive patients (HT), oxidative stress, measured as 8-ISO-prostaglandin F2alpha (8-ISO-PGF2alpha), should raise paralleling decreasing renal function and should correlate with estimated glomerular filtration rate (eGFR).
In 626 HT with renal function ranging from stages 1 to 5 and 100 healthy controls, plasma levels of 8-ISO-PGF2alpha, high-sensitivity C-reactive protein (CRP), transforming growth factor-beta (TGF-beta) and endothelin-1 (ET-1) were measured. GFR was estimated by the Modification of Diet in Renal Disease study equation.
When HT were stratified according to renal function stages, 8-ISO-PGF2alpha, CRP, TGF-beta and ET-1 increased progressively and significantly with decreasing eGFR. The multiple regression analysis, considering eGFR as a dependent variable, showed that 8-ISO-PGF2alpha (beta = -0.361, P < 0.000001), ET-1 (beta = -0.197, P < 0.0001) and TGF-beta (beta = -0.170, P < 0.0004) correlated independently with eGFR. All biomarkers were good predictors of eGFR <60 ml/min/1.73 m(2) [receiver-operator-curve (ROC) areas]. ET-1 was shown to be the best predictor with a ROC area = 0.938; with a threshold of 4 pg/ml, 91% sensitivity and 85% specificity were observed, whereas 8-ISO had a ROC area = 0.931, and for a threshold of 329 pg/ml, sensitivity and specificity were 89%, respectively. In contrast, CRP showed the lower predictive value with a ROC area = 0.917; with a threshold of 2.52 mg/l, an 87% sensitivity and an 83% specificity were obtained.
Our findings are a clear-cut demonstration of a strong and negative correlation of both oxidative stress and ET-1 with renal function stages in HT. ET-1 and 8-isoprostane are predictive of eGFR.
高血压及其他非传统危险因素可直接损害肾脏，并通过促进动脉粥样硬化形成间接损害肾脏。有证据表明，氧化应激和炎症增加可能在很大程度上介导了危险因素对肾脏的影响。我们假设，在高血压患者（HT）中，以8-异前列腺素F2α（8-ISO-PGF2α）衡量的氧化应激应与肾功能下降平行升高，并应与估算肾小球滤过率（eGFR）相关。
对626例肾功能处于1至5期的高血压患者和100例健康对照者，检测其血浆8-ISO-PGF2α、高敏C反应蛋白（CRP）、转化生长因子-β（TGF-β）和内皮素-1（ET-1）水平。采用肾脏病膳食改良研究方程估算肾小球滤过率。
根据肾功能分期对高血压患者进行分层时，随着eGFR下降，8-ISO-PGF2α、CRP、TGF-β和ET-1逐渐显著升高。以eGFR作为因变量的多元回归分析显示，8-ISO-PGF2α（β = -0.361，P < 0.000001）、ET-1（β = -0.197，P < 0.0001）和TGF-β（β = -0.170，P < 0.0004）与eGFR独立相关。所有生物标志物都是eGFR <60 ml/min/1.73 m²的良好预测指标[受试者操作特征曲线（ROC）面积]。ET-1被证明是最佳预测指标，ROC面积 = 0.938；阈值为4 pg/ml时，敏感性为91%，特异性为85%，而8-ISO的ROC面积 = 0.931，阈值为329 pg/ml时，敏感性和特异性分别为89%。相比之下，CRP的预测价值较低，ROC面积 = 0.917；阈值为2.52 mg/l时，敏感性为87%，特异性为83%。
我们的研究结果明确表明，氧化应激和ET-1与高血压患者的肾功能分期呈强烈负相关。ET-1和8-异前列腺素可预测eGFR。
