Pathobiology of Kidney Disease: Role of Iron

描述（由申请方提供）：本项目的长期目标是评估慢性肾脏疾病（CKD）患者常用的肠外铁剂治疗导致的肾小球滤过率下降。我们假设，在轻度至中度CKD受试者中，与口服铁剂相比，静脉输注铁剂（MR）将产生氧化应激并引起炎症反应，与口服铁剂相比，这将与肾小球滤过率（GFR）更快下降相关。静脉铁剂与口服铁剂的比较将允许检验MR对肾脏有害的假设。具体目标：我们将直接检验MR将在短期内产生炎症反应和蛋白尿的假设，与口服铁相比，这将直接导致GFR的长期下降率更高。我们假设，静脉注射1克铁8周后，与随机接受口服铁剂治疗的患者相比，静脉注射铁剂治疗的患者蛋白尿（和GFR下降）记录的肾损伤将增加。方法：采用随机、平行、对照试验。将通过碘酞酸清除率在200名参与者中每6个月测量一次GFR，持续两年。意义：静脉铁剂是常用的，可能是CKD患者肾损伤的一种机制。项目的新奇性和健康相关性：该提案将提供关于静脉铁剂对CKD患者肾脏疾病进展作用的转化数据。

DESCRIPTION (provided by applicant): The long-term goal of this project is to assess the fall in glomerular filtration rate attributable to the commonly utilized therapy of parenteral iron in patients with chronic kidney disease (CKD). We hypothesize that in subjects with mild to moderate CKD, infusion of intravenous iron (MR) when compared to oral iron, will generate oxidative stress and cause an inflammatory response that will be associated with a more rapid decline in glomerular filtration rate (GFR) compared to oral iron. Comparison of IV iron with oral iron will allow testing the hypothesis that MR is injurious to the kidney. Specific aims: We will directly test the hypothesis that MR will generate an inflammatory response and albuminuria in the short-term, that will directly lead to a greater rate of fall in GFR, in the long-term, compared to oral iron. We hypothesize that after administration of one gram of IV iron over a course of 8 weeks, renal injury as documented by albuminuria (and fall in GFR) will be increased with IV iron sucorse therapy compared to those randomized to oral iron therapy. Methods: A randomized, parallel group, controlled trial will be performed. GFR will be measured every 6 months for two years in 200 participants by iothalamate clearances. Significance: Intravenous iron is commonly utilized and is likely a mechanism of renal injury in patients with CKD. Novelty and Health Relatedness of the Project: This proposal will provide translational data on the role of intravenous iron to progression of kidney disease in patients with CKD.