NDT Advance Access published online on September 4, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn489
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Endothelin-1 and F2-isoprostane relate to and predict renal dysfunction in hypertensive patients
1 Cattedra di Nefrologia e U.O. di Malattie Renali ed Ipertensione Arteriosa 2 Cattedra di Medicina Interna, Hypertension Excellence Centre of the European Society of Hypertension, Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Università di Palermo, Palermo, Italy
Correspondence and offprint requests to: Santina Cottone, Via del Vespro 129, 90127 Palermo, Italy. Tel: +39-0916554333; Fax: +39-0916554331; E-mail: sancott{at}tin.it
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Abstract |
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Background. 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).
Methods. 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.
Results. 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 (β = –0.361, P < 0.000001), ET-1 (β = –0.197, P < 0.0001) and TGF-beta (β = –0.170, P < 0.0004) correlated independently with eGFR. All biomarkers were good predictors of eGFR <60 ml/min/1.73 m2 [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.
Conclusions. 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.
Keywords: atherosclerosis; endothelium; inflammation; oxidative stress; renal dysfunction
Received for publication: 4. 3.08
Accepted in revised form: 6. 8.08