Dysregulated Mineral Metabolism in Acute Kidney Injury

急性肾损伤时矿物质代谢失调

基本信息

批准号：
8702918
负责人：
David Evan Leaf
金额：
$ 6.37万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-30 至 2015-06-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8702918
关键词：
Acute Renal Failure with Renal Papillary Necrosis Affect Animals Attenuated Biochemical Markers Biological Markers Blood Calcitriol Cardiac Surgery procedures Cardiovascular Diseases Chronic Kidney Failure Clinical Cohort Studies Critical Illness Data Development Double-Blind Method End stage renal failure Enrollment Functional disorder Goals Host Defense Hour Human Human Cell Line Hyperparathyroidism Hypocalcemia result Immune Immune system Immunity Infection Inflammation Inflammatory Injury Interleukin-6 Kidney Measures Metabolism Minerals Modeling Natural Immunity Observational Study Outcome Participant Patients Pharmaceutical Preparations Physiological Pilot Projects Placebo Control Placebos Plasma Play Postoperative Period Production Proteinuria Randomized Randomized Controlled Trials Renin-Angiotensin System Reporting Research Design Risk Risk Factors Role Sampling Sepsis Septic Shock Testing Urine Vitamin D Vitamin D Deficiency adverse outcome cathelicidin cathelicidin antimicrobial peptide cytokine fibroblast growth factor 23 improved inflammatory marker mortality novel public health relevance rat KIM-1 protein urinary

项目摘要

DESCRIPTION (provided by applicant): Dysregulated mineral metabolism is a universal feature of advanced chronic kidney disease (CKD) and is strongly associated with an increased burden of cardiovascular disease. In acute kidney injury (AKI), in contrast, relatively little is known about mineral metabolism. Our preliminary data indicate that many of the abnormalities in mineral metabolism that are observed in CKD, such as hypocalcemia, hyperphosphatemia, hyperparathyroidism, elevated Fibroblast Growth Factor-23 (FGF23), and vitamin D deficiency are also observed in AKI. Whether these derangements in mineral metabolism are associated with adverse outcomes in AKI, as they are in CKD, and whether intervening on them might impact clinical outcomes, has not been rigorously studied. We propose to study derangements in mineral metabolism in two groups of patients with AKI: AKI resulting from sepsis and AKI occurring after cardiac surgery. Among patients with sepsis and AKI, vitamin D deficiency is common and is strongly associated with adverse outcomes. Vitamin D has important effects on immunity and inflammation. We propose a pilot study evaluating the effects of activated vitamin D on immune, inflammatory, and renal injury biomarkers among critically-ill patients with sepsis with or without AKI. We will enroll 60 patients and randomly assign them 1:1 to receive a single administration of calcitriol 2mcg IV versus placebo. Participants with AKI will be stratified in equal numbers into the two groups. We will collect plasma and urine at 0, 6, 24, and 48 hours after study drug administration. We will test the hypotheses that calcitriol administration, compared to placebo, will result in favorable effects on markers of innate immunity and inflammation, identified by an increase in plasma cathelicidin and a decrease in plasma IL-6 levels, and will protect against AKI, identified by a decrease in urinary KIM-1 levels. Elevated FGF23 levels are associated with increased mortality in CKD and ESRD but have not been studied in detail in AKI. We propose to study FGF23 as a biomarker of adverse outcomes in cardiac surgery-associated AKI. We will use a case-cohort study design, comparing FGF23 levels among cases (those who develop AKI after cardiac surgery) to non- cases. We will test the hypothesis that elevated plasma FGF23 levels are an independent predictor of the composite clinical outcome of mortality or sustained kidney injury 90 days following cardiac surgery.

描述（由申请人提供）：矿物质代谢失调是晚期慢性肾病（CKD）的普遍特征，并且与心血管疾病负担增加密切相关。相比之下，在急性肾损伤（AKI）中，人们对矿物质代谢知之甚少。我们的初步数据表明，在 CKD 中观察到的许多矿物质代谢异常，例如低钙血症、高磷血症、甲状旁腺功能亢进、成纤维细胞生长因子 23 (FGF23) 升高和维生素 D 缺乏，在 AKI 中也观察到。矿物质代谢的这些紊乱是否与 AKI 的不良后果相关（就像 CKD 中的不良后果一样），以及对其进行干预是否可能影响临床结果，尚未得到严格研究。我们建议研究两组 AKI 患者的矿物质代谢紊乱：脓毒症引起的 AKI 和心脏手术后发生的 AKI。在脓毒症和 AKI 患者中，维生素 D 缺乏很常见，并且与不良后果密切相关。维生素 D 对免疫和炎症具有重要作用。我们提出了一项初步研究，评估活化维生素 D 对伴有或不伴有 AKI 的脓毒症危重患者的免疫、炎症和肾损伤生物标志物的影响。我们将招募 60 名患者，并以 1:1 的比例随机分配他们接受单次骨化三醇 2mcg IV 给药与安慰剂治疗。患有 AKI 的参与者将按同等数量分为两组。我们将在研究药物给药后 0、6、24 和 48 小时收集血浆和尿液。我们将测试以下假设：与安慰剂相比，骨化三醇给药将对先天免疫和炎症标志物产生有利影响（通过血浆导管素增加和血浆 IL-6 水平降低来确定），并且将预防 AKI（确定）尿 KIM-1 水平降低。 FGF23 水平升高与 CKD 和 ESRD 死亡率增加相关，但尚未在 AKI 中进行详细研究。我们建议研究 FGF23 作为心脏手术相关 AKI 不良后果的生物标志物。我们将采用病例队列研究设计，比较病例（心脏手术后发生 AKI 的患者）与非病例之间的 FGF23 水平。我们将检验以下假设：血浆 FGF23 水平升高是心脏手术后 90 天死亡或持续肾损伤的综合临床结果的独立预测因子。