Maria Carmela Lorito

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.

Association between biomarkers of inflammation and left ventricular hypertrophy in moderate chronic kidney disease

AIMS Left ventricular hypertrophy (LVH) is a predictor for cardiovascular mortality, and it is considered to be a surrogate marker of preclinical cardiovascular disease. This study aimed at evaluating whether fetuin-A plasma levels are decreased in patients with moderate chronic kidney disease (CKD) and their linkage to plasma concentrations of hs-C-reactive protein (CRP), cardiotrophyn-1 (CT-1), tumor necrosis factor-ac (TNF-alpha), propeptide of collagen Type I (PIP) and to LVH. MATERIAL AND METHODS We enrolled 64 moderate CKD and 55 essential hypertensives (EH) with normal renal function as controls. All the patients underwent an echocardiographic examination; plasma samples were obtained to measure routine clinical parameters and the molecules listed above (measured by ELISA). RESULTS Among CKD there were 30/64 patients with LVH, and in EH group 14/55 subjects had LVH. Fetuin A was reduced in CKD when compared with EH (p < 0.0001). The comparison between CKD having LVH with those without LVH showed significant differences in plasma levels of fetuin-A (p < 0.002), TNF-alpha (p < 0.01) and hs-CRP (p < 0.001), CT-1 and PIP (p < 0.002). CKD with LVH had lower values of fetuin-A (p < 0.001), and higher values of hs-CRP (p < 0.001) TNF-alpha (p < 0.001), CT-1 (p < 0.001) and PIP (p < 0.001) than EH with LVH. The multivariate analysis of correlation demonstrated that in CKD patients hs-CRP (beta 0.42, p < 0.00006), and systolic blood pressure (beta 0.29, p < 0.02) were independent predictors of LV mass index. The relationship between LV mass index and fetuin-A did not reach statistical significance. CONCLUSIONS For the first time in moderate CKD patients, we demonstrate that fetuin-A is decreased and relates to LVH depending on C-reactive protein.

Microalbuminuria and early endothelial activation in essential hypertension

We hypothesized that in essential hypertensive patients (EHs), plasma levels of pro-atherogenic adhesion molecules would be increased and related with urine albumin excretion (UAE). Thus, this study was aimed at evaluating biochemical markers of endothelial activation and their relationship with UAE in a group of patients with uncomplicated EH. In basal condition soluble forms of adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, as well as 24-h UAE were assayed. One hundred patients with essential hypertension and no diabetes or ultrasonographic evidence of atherosclerosis were included in the study. Seventy normotensive healthy subjects served as controls. EHs were first studied overall, than were divided into two subgroups: those with UAE ⩾20 mcg/min MAUs and those with UAE <20 mcg/min (non-MAUs). ICAM-1 (P<0.001) and VCAM-1 (P<0.0001) plasma concentrations were higher in EHs than in controls. Microalbuminuric EHs had greater levels of adhesion molecules than non-MAUs (ICAM-1 P=0.04; VCAM-1 P=0.02, respectively). In EHs UAE was correlated with ICAM-1 (r=0.29, P=0.003), and VCAM-1 (r=0.30, P=0.002). These associations were confirmed in multiple regression models (P=0.02 for both ICAM-1 and VCAM-1) including, along with adhesion molecules, age, body mass index and blood pressures. Our findings show that in essential hypertension there is a very early activation of endothelial adhesion molecules favouring atherosclerosis.

C-reactive protein and intercellular adhesion molecule-1 are stronger predictors of oxidant stress than blood pressure in established hypertension.

Background Oxidant stress is implicated in the pathogenesis of atherosclerosis in cardiovascular diseases. Our aim was to test oxidative stress, as 8-iso-prostaglandin F2α (8-iso-PGF2α), and its relationship with inflammation markers C-reactive protein (CRP) and tumour necrosis factor-α (TNFα), and endothelial activation assayed as soluble intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in essential hypertension. Methods In 216 essential hypertensive patients and 55 healthy control individuals, plasma levels of high-sensitivity CRP and TNFα, 8-iso-PGF2α, ICAM-1 and VCAM-1 were measured in basal conditions. Moreover, basal and 24-h ambulatory blood pressure monitoring measurements were obtained. Results Essential hypertensive patients showed higher levels of 8-iso-PGF2α (P < 0.0001), high-sensitivity CRP, TNFα, ICAM-1 and VCAM-1 (P < 0.001, respectively) than control individuals. In control individuals, 8-iso-PGF2α correlated only with high-sensitivity CRP (P < 0.001). In essential hypertensive patients, 8-iso-PGF2α correlated with high-sensitivity CRP (P < 0.000001), TNFα (P < 0.0001), ICAM-1 (P < 0.000001), VCAM-1 (P < 0.0001) and blood pressure. The multiple regression analysis considering 8-iso-PGF2α as the dependent variable showed that in essential hypertensive patients the independent predictors of 8-iso-PGF2α were ICAM-1, high-sensitivity CRP (P < 0.00001, respectively), and TNFα (P = 0.028). Conclusion Our findings demonstrate that oxidant stress is increased in essential hypertension, and relates to inflammation and endothelial activation. Factors other than blood pressure are stronger predictors of oxidant stress.

Parathyroid hormone is inversely related to endothelin-1 in patients on haemodialysis

Aim:  Parathyroid hormone secretion is mainly influenced by hypocalcaemia, hyperphosphataemia and vitamin D deficiency. However, previous in vitro and in vivo studies showed that endothelin‐1 can influence parathyroid hormone secretion. This study was aimed at evaluating this relationship in vivo in uraemic patients.