The Cardiovascular and Renal Toxicity of Aldosterone

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Recent research suggests a novel intervention in chronic kidney disease (CKD) by the use of mineralcorticoid receptor antagonism (MRA) and epithelial sodium channel (ENaC) blockade. It is hypothesized that aldosterone, via activation of the ENaC, has effects in multiple cellular lines acts as a hormonal mediator in the pathogenesis of CKD by increasing endothelial dysfunction and inflammation. My proposal will utilize the existing infrastructure of an ongoing NIH, RO-1 supported clinical trial in diabetic nephropathy. I propose to elucidate the mechanism of toxicity by measuring urinary and serum markers of inflammation, oxidative stress and endothelial dysfunction in patients receiving ACEi + MRA, compared to ACEi-based alone. A small number of patients within this trial will be recruited at study completion to assess benefit with add-on ENaC blockade (amiloride) + ACEi by measurement of the aforementioned markers. There is no data on mechanism of benefit of MRA in CKD and no data, at all, in the use of amiloride in CKD. The results of this trial will help to define the future roles of MRA and ENaC blockade in CKD/ESRD, disease states plagued with increased cardiovascular mortality from a known inflammatory state.