Association Between Kidney Function, Plasma Endotheline-1 (ET1) Levels, and Nontraditional Cardiovascular Risk Factors in Metal Mines Workers

Abstract

SESSION TITLE: Cardiovascular 2 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: To assess possible relationships between renal function parameters, ET1 levels and nontraditional cardiovascular risk factors and to test the hypothesis that occupational exposure to heavy metals (HM) has harmful effects on the kidney and vessels, on historical mines areas in the North-Western part of Romania. The mineral assemblages include native elements like gold, silver, copper, arsenic, cadmium, lead, mercury, zinc, free silica, nickel, asbestos, sulphur, manganase, cobalt. The mechanisms of biological interaction of HM are uncertain and poorly understood. Heavy metals enters many types of cells where bind to oxygen, nitrogen, and sulfhydryl groups in proteins, resulting alterations of enzymatic activity and oxidative stress damage through the accumulation of reactive oxygen species, enhanced lipid peroxidation and endothelial dysfunction, an early step in the development of atherosclerosis. METHODS: We conducted a follow-up prospective study of 44 cases mean aged 43.75±4.97 year-old, with a mean period of HM exposure of 16.88±4.45 years versus 26 individuals nonexposed mean aged 50.5±6.81 year-old. Demographic, anthropometric, smoking history, plasma ET1, lipid profile, uric acid, C-Reactive Protein (CRP), fibrinogen, thrombocytes, glycemia and albumin levels were performed. Kidney function was determined by serum creatinine and urea, urine albumin excretion rate (AER), urea/creatinine ratio (UCR), albumin/creatinine ratio (ACR) and creatinine clearance, as an estimate of Glomerular Filtration Rate (eGFR), calculated according to the Cockcroft and Gault and Modification of Diet in Renal Disease equation formulas. Cardiovascular disease risk was evaluated through Reynolds Risk Score (RRS). Statistical analysis included Spearman correlations tests, t test and one-way ANOVA test. RESULTS: ET1 (p=0.0001), ACR (p=0.03), AER (p=0.009), uric acid (p=0.0003), thrombocytes (p=0.009), glycemia (p=0.003) and RRS (p=0.0006) were significantly higher, while eGFR (p=0.0001) lower, in patients versus controls. In miners group, we have found correlations between eGRF and uric acid (r=0.43;p=0.003), thrombocytes (r=0.32;p=0.03); AER and ET1 (r=-0.29;p=0.04), fibrinogen (r=-0.32;p=0.03), glycemia (r=0.33;p=0.02); UCR and uric acid (r=0.36;p=0.01); ACR and CRP (r=-0.31;p=0.03); creatinine and uric acid (r=-0.41;p=0.005), thrombocytes (r=-0.35;p=0.01). CONCLUSIONS: In metal mines workers, the nontraditional risk factors can be considered as promoters of atherosclerosis and renal disease progresssion with a high predictive value for cardiovascular disease. ET1 and uric acid may be used as biomarkers for early kidney disease and, perhaps would help to stratify their risk to adjust the pharmacological management. CLINICAL IMPLICATIONS: Chronic occupational exposure to HM cause toxic effects on the kidneys, thus becoming a major public health concern and a step forward for disease prevention. DISCLOSURE: The following authors have nothing to disclose: Ligia Puiu, Ancuta Petrovan, Roxana Nemes, Florin Mihaltan, Ovidiu Fira-Mladinescu, Oana Deleanu, Ruxandra Ulmeanu No Product/Research Disclosure Information