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10.1161/JAHA.114.001624 http://scihub22266oqcxt.onion/10.1161/JAHA.114.001624 C4392442!4392442 !25801761     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25801761 &cmd=llinks): Failed to open stream: HTTP request failed! 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Plasma pro-endothelin-1 peptide concentrations rise in chronic kidney disease and following selective endothelin A receptor antagonism |pdf=|usr=}}{{25801761 }} gab.com Text Plasma pro-endothelin-1 peptide concentrations rise in chronic kidney disease and following selective endothelin A receptor antagonism JO: J Am Heart Assoc http://www.kidney.de/pget.php?&tw=1&pmid=25801761 #FOAvip BACKGROUND: Endothelin 1 (ET-1) contributes to chronic kidney disease (CKD) development and progression, and endothelin receptor antagonists are being investigated as a novel therapy for CKD. The proET-1 peptides, endothelin-like domain peptide (ELDP) and C-terminal pro-ET-1 (CT-proET-1), are both potential biomarkers of CKD and response to therapy with endothelin antagonists. METHODS AND RESULTS: We assessed plasma and urine ELDP and plasma CT-proET-1 in CKD patients with minimal comorbidity. Next, in a randomized double-blind crossover study of 27 subjects with proteinuric CKD, we examined the effects of 6 weeks of treatment with placebo, sitaxentan (endothelin A antagonist), and nifedipine on these peptides alongside the primary end points of proteinuria, blood pressure, and arterial stiffness. Plasma ELDP and CT-proET-1 increased with CKD stage (both P<0.0001), correlating inversely with estimated glomerular filtration rate (both P<0.0001). Following intervention, placebo and nifedipine did not affect plasma and urine ELDP or plasma CT-proET-1. Sitaxentan increased both plasma ELDP and CT-proET-1 (baseline versus week 6±SEM: ELDP, 11.8±0.5 versus 13.4±0.6 fmol/mL; CT-proET-1, 20.5±1.2 versus 23.3±1.5 fmol/mL; both P<0.0001). Plasma ET-1 was unaffected by any treatment. Following sitaxentan, plasma ELDP and CT-proET-1 correlated negatively with 24-hour urinary sodium excretion. CONCLUSIONS: ELDP and CT-proET-1 increase in CKD and thus are potentially useful biomarkers of renal injury. Increases in response to endothelin A antagonism may reflect EDN1 upregulation, which may partly explain fluid retention with these agents. CLINICAL TRIAL REGISTRATION: URL: www.clinicalTrials.gov Unique identifier: NCT00810732. Twit Text FOAVip Plasma pro-endothelin-1 peptide concentrations rise in chronic kidney disease and following selective endothelin A receptor antagonism ????J Am Heart Assoc http://www.kidney.de/pget.php?&tw=1&pmid=25801761 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25801761 #FOAvip English Wikipedia <ref>{{Cite pmid|25801761 }}</ref> Plasma pro-endothelin-1 peptide concentrations rise in chronic kidney disease and following selective endothelin A receptor antagonism #MMPMID25801761 Dhaun N ; Yuzugulen J ; Kimmitt RA ; Wood EG ; Chariyavilaskul P ; MacIntyre IM ; Goddard J ; Webb DJ ; Corder R J Am Heart Assoc 2015[Mar]; 4 (3 ): e001624 PMID25801761 show ga BACKGROUND: Endothelin 1 (ET-1) contributes to chronic kidney disease (CKD) development and progression, and endothelin receptor antagonists are being investigated as a novel therapy for CKD. The proET-1 peptides, endothelin-like domain peptide (ELDP) and C-terminal pro-ET-1 (CT-proET-1), are both potential biomarkers of CKD and response to therapy with endothelin antagonists. METHODS AND RESULTS: We assessed plasma and urine ELDP and plasma CT-proET-1 in CKD patients with minimal comorbidity. Next, in a randomized double-blind crossover study of 27 subjects with proteinuric CKD, we examined the effects of 6 weeks of treatment with placebo, sitaxentan (endothelin A antagonist), and nifedipine on these peptides alongside the primary end points of proteinuria, blood pressure, and arterial stiffness. Plasma ELDP and CT-proET-1 increased with CKD stage (both P<0.0001), correlating inversely with estimated glomerular filtration rate (both P<0.0001). Following intervention, placebo and nifedipine did not affect plasma and urine ELDP or plasma CT-proET-1. Sitaxentan increased both plasma ELDP and CT-proET-1 (baseline versus week 6±SEM: ELDP, 11.8±0.5 versus 13.4±0.6 fmol/mL; CT-proET-1, 20.5±1.2 versus 23.3±1.5 fmol/mL; both P<0.0001). Plasma ET-1 was unaffected by any treatment. Following sitaxentan, plasma ELDP and CT-proET-1 correlated negatively with 24-hour urinary sodium excretion. CONCLUSIONS: ELDP and CT-proET-1 increase in CKD and thus are potentially useful biomarkers of renal injury. Increases in response to endothelin A antagonism may reflect EDN1 upregulation, which may partly explain fluid retention with these agents. CLINICAL TRIAL REGISTRATION: URL: www.clinicalTrials.gov Unique identifier: NCT00810732. |Adult [MESH] |Biomarkers/blood/urine [MESH] |Blood Pressure/drug effects [MESH] |Calcium Channel Blockers/adverse effects/therapeutic use [MESH] |Cross-Over Studies [MESH] |Double-Blind Method [MESH] |Endothelin A Receptor Antagonists/*therapeutic use [MESH] |Endothelin-1/*blood/urine [MESH] |Female [MESH] |Humans [MESH] |Isoxazoles/adverse effects/*therapeutic use [MESH] |Male [MESH] |Middle Aged [MESH] |Nifedipine/therapeutic use [MESH] |Protein Precursors/*blood/urine [MESH] |Proteinuria/blood/drug therapy [MESH] |Receptor, Endothelin A/*drug effects/metabolism [MESH] |Renal Insufficiency, Chronic/blood/diagnosis/*drug therapy/physiopathology [MESH] |Scotland [MESH] |Thiophenes/adverse effects/*therapeutic use [MESH] |Time Factors [MESH] |Treatment Outcome [MESH] |Up-Regulation [MESH]Plasma pro-endothelin-1 peptide concentrations rise in chronic kidney (epmc).pdf DeepDyve Pubget Overpricing