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

Francesco Vaccaro, Giovanni Cerasola, Giuseppe Mule', Emilio Nardi, Marco Guarneri, Raffaella Riccobene, Santina Cottone, Paola Cusimano, Santina Cottone, Alessandro Palermo, Anna Vadala', Maria Carmela Lorito, Rosalia Arsena

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)497-503
Number of pages7
JournalNEPHROLOGY DIALYSIS TRANSPLANTATION
Volume24
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

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