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【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.
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The relationship between the levels of renalase and changes in proteinuria,hypertension,renal function,renal tubular epithelial cell apoptosis and B-cell lymphoma-2 (Bcl-2) expression was investigated in patients (chronic nephritis,primary nephrotic syndrome or other kidney disease) that underwent renal biopsy.The study group comprised 72 patients undergoing renal biopsy.Patient profiles and renal function were collected.Concentrations of renalase and Bcl-2 were measured by immunohistochemistry.Tubular injury was detected by periodic acid Schiff staining (PAS) and renal tubular epithelial cell apoptosis was assessed by TUNEL assay.The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues.There was a positive linear relationship between renalase and some serum and cardiac indices;a negative correlation was found between age,eGFR,Ccr and 24-h urinary protein.Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase.The results showed that renalase probably increased the expression of Bcl-2.By two independent samples t-test,renalase levels were significantly increased in the non-hypertension group than in the hypertension group.One-way ANOVA showed that renalase expression was higher in samples with Lee's grade Ⅲ than in those with Lee's grade V.The expression of renalase was significantly decreased in patients who underwent renal biopsy,and was also associated with blood and renal function.The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway,finally achieving the purpose of delaying the progress of renal failure.
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The relationship between the levels of renalase and changes in proteinuria,hypertension,renal function,renal tubular epithelial cell apoptosis and B-cell lymphoma-2 (Bcl-2) expression was investigated in patients (chronic nephritis,primary nephrotic syndrome or other kidney disease) that underwent renal biopsy.The study group comprised 72 patients undergoing renal biopsy.Patient profiles and renal function were collected.Concentrations of renalase and Bcl-2 were measured by immunohistochemistry.Tubular injury was detected by periodic acid Schiff staining (PAS) and renal tubular epithelial cell apoptosis was assessed by TUNEL assay.The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues.There was a positive linear relationship between renalase and some serum and cardiac indices;a negative correlation was found between age,eGFR,Ccr and 24-h urinary protein.Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase.The results showed that renalase probably increased the expression of Bcl-2.By two independent samples t-test,renalase levels were significantly increased in the non-hypertension group than in the hypertension group.One-way ANOVA showed that renalase expression was higher in samples with Lee's grade Ⅲ than in those with Lee's grade V.The expression of renalase was significantly decreased in patients who underwent renal biopsy,and was also associated with blood and renal function.The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway,finally achieving the purpose of delaying the progress of renal failure.
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Objective To assess the roles of renalase and renal sympathetic nerve activity in patients with chronic heart failure (CHF). Methods Plasma renin activity (PRA), angiotensinⅠ (AngⅠ), angiotensin Ⅱ(AngⅡ),adrenaline (E), noradrenaline (NE) and renalase were determined in 60 patients with CHF (CHF group) and in 42 healthy cases (control group). Data were compared between patients with mild and serious CHF. Results PRA, E, NE and AngⅠincreased and renalase decreased in CHF group than those in control group. Compared with mild CHF, renalase and left ventricular ejection fraction decreased (P < 0.01, 0.034), while N-terminal pro-B-type natriuretic peptide (NT-proBNP) and PRA significantly increased (P<0.01). Linear correlation analysis showed that renalase was inversely correlated with Log NT-proBNP (r = -0.400, P = 0.002) and Log NE (r=-0.314, P = 0.014). Logistic regression analysis showed that NT-proBNP (OR = 6.963, 95%CI = 1.223 to 39.638), PRA (OR = 3.736, 95%CI = 1.031 to 13.540) and renalase (OR = 0.253, 95%CI = 0.069 to 0.927) were associated with increased NYHA classes. Conclusions PRA would increase while renalase would decrease in patients with CHF. PRA and renalase were correlated to the severity of CHF.
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@#The latest reports showed that kidney secrets a new type protein:renalase,a novel flavin adenine dinucleotide-dependent(FAD-dependent)amine oxidase which is secreted into the blood by the kidney and regulates heart function and blood pressure by metabolizing catecholamines.Kidney disease is associated with cardiovascular disease,so people pay more and more attentions to renalase.This article will introduce the structure and mechanism of renalase,and propose its future.