Endothelin-1 and F2-isoprostane relate to and predict renal dysfunction in hypertensive patients

Background. Hypertension and additional non-traditionalrisk factors can damage the kidney directly and by promotingatherogenesis. Evidence indicates that increased oxidativestress and inflammation may mediate a large part of theeffects of risk factors on the kidney. We hypothesized thatin hypertensive patients (HT), oxidative stress, measured as8-ISO-prostaglandin F2alpha (8-ISO-PGF2alpha), shouldraise paralleling decreasing renal function and should correlatewith estimated glomerular filtration rate (eGFR).Methods. In 626 HT with renal function ranging fromstages 1 to 5 and 100 healthy controls, plasma levelsof 8-ISO-PGF2alpha, high-sensitivity C-reactive protein(CRP), transforming growth factor-beta (TGF-beta) andendothelin-1 (ET-1) were measured. GFR was estimated bythe Modification of Diet in Renal Disease study equation.Results. When HT were stratified according to renal functionstages, 8-ISO-PGF2alpha, CRP, TGF-beta and ET-1increased progressively and significantly with decreasingeGFR.The multiple regression analysis, considering eGFR asa 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) correlatedindependently with eGFR. All biomarkers were good predictorsof eGFR <60 ml/min/1.73 m2 [receiver-operatorcurve(ROC) areas]. ET-1was shown to be the best predictorwith 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 329pg/ml, sensitivity and specificity were 89%, respectively.In contrast, CRP showed the lower predictive value with aROC 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 demonstrationof a strong and negative correlation of both oxidative stressand ET-1 with renal function stages in HT. ET-1 and 8-isoprostane are predictive of eGFR.