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


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.
Cottone
Santina
S
Cattedra di Nefrologia e U.O. di Malattie Renali ed Ipertensione Arteriosa, Italy. sancott@tin.it
Mulè
Giuseppe
G
Guarneri
Marco
M
Palermo
Alessandro
A
Lorito
Maria C
MC
Riccobene
Raffaella
R
Arsena
Rosalia
R
Vaccaro
Francesco
F
Vadalà
Anna
A
Nardi
Emilio
E
Cusimano
Paola
P
Cerasola
Giovanni
G
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000097:blood
D019332:Endothelin-1; D016212:Transforming Growth Factor beta; C075750:8-epi-prostaglandin F2alpha; D002097:C-Reactive Protein; D015237:Dinoprost