Pathobiology of Kidney Disease: Role of Iron

描述(由申请人提供)：该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的下降。我们假设，在轻中度CKD患者中，与口服铁相比，静脉注射铁(MR)将产生氧化应激并引起炎症反应，与口服铁相比，肾小球滤过率(GFR)下降更快。将静脉注射铁与口服铁进行比较，可以检验MR对肾脏有损害的假设。具体目标：我们将直接测试MR将在短期内产生炎症反应和蛋白尿的假设，这将直接导致GFR在长期内比口服铁更大的下降率。我们假设，在8周的疗程中，静脉注射1克铁后，与随机口服铁剂治疗相比，静脉注射蔗糖铁治疗会增加蛋白尿(和肾小球滤过率下降)所记录的肾脏损伤。方法：采用随机平行分组对照试验。在两年的时间里，200名参与者将每6个月测量一次肾小球滤过率，通过硫柳汞清除法。意义：静脉铁是CKD患者常用的铁，可能是肾损伤的一种机制。项目的新颖性和健康相关性：该提案将提供有关静脉补铁在慢性肾脏病患者肾脏疾病进展中的作用的翻译数据。

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.