Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD

姜黄素疗法治疗 ADPKD 儿童和年轻人的血管功能障碍

• 批准号: 9754811
• 负责人: Kristen Lynn Nowak
• 金额: $ 15.13万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754811
• 关键词: Acute; Adult; Affect; Age; Age-Years; American; Antioxidants; Aorta; Arteries; Ascorbic Acid; Autosomal Dominant Polycystic Kidney; Biological; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Cause of Death; Child; Childhood; Conduct Clinical Trials; Curcumin; Cyst; Cystic Kidney Diseases; Cystic kidney; Data; Development; Disease; Disease Progression; Double-Blind Method; Double-blind trial; Effectiveness; Endothelium; Event; Functional disorder; Future; Genetic Diseases; Genetic Transcription; Goals; Growth; Health; Human; Hypertension; Impairment; In Vitro; Inflammation; Infusion procedures; Kidney; Kidney Diseases; Life; MRI Scans; Magnetic Resonance Imaging; Mass Spectrum Analysis; Measures; Mediating; Methods; Nature; Nutraceutical; Oral; Oxidative Stress; Patients; Physiologic pulse; Physiological; Placebos; Population; Prognostic Marker; Randomized; Randomized Clinical Trials; Renal function; Research; Rodent Model; Spices; Testing; Therapeutic; Tumeric; Urine; Vascular Diseases; aged; arterial stiffness; brachial artery; cardiovascular disorder prevention; endothelial dysfunction; improved; in vivo; insight; kidney cell; mortality; novel; patient subsets; polyphenol; prevent; public health relevance; vascular endothelial dysfunction; young adult

 DESCRIPTION (provided by applicant): Although often considered to be a disease of adults, complications of ADPKD begin in childhood. While the hallmark of ADPKD is the development and continued growth of multiple renal cysts that result in ultimate loss of kidney function, the leading cause of death among affected patients is cardiovascular in nature. Vascular dysfunction (endothelial dysfunction and large elastic artery stiffness) is evident very early in te course of the disease and appears to involve increased oxidative stress and inflammation. Treatment options to prevent CVD in adults with ADPKD are limited, thus childhood may represent a key therapeutic window. Curcumin is a safe, naturally occurring polyphenol found in the Indian spice turmeric that has a unique ability to activate transcription of key antioxidants, suppress inflammation, and reduce proliferation. Aim 1 will assess the efficacy of curcumin (25 mg/kg/day) for improving vascular function in children and young adults (6-22 years of age) with ADPKD, using a 1 year randomized, placebo-controlled, double-blind trial. Aim 2 will determine (in a sub-group of patients 18-22 years of age), if improvements are associated with reduced oxidative stress and inflammation, utilizing state of the art mass spectrometry methods. A third exploratory aim will assess changes in total kidney volume using MRI scans. This study has the potential to establish a novel, safe, and easy to deliver therapy for the treatment of arterial dysfunction, and possibly renal cystic disease, in an understudied population of children and young adults with ADPKD.

 描述（由申请人提供）：虽然 ADPKD 通常被认为是一种成人疾病，但其并发症始于儿童期。虽然 ADPKD 的特点是多发性肾囊肿的发展和持续生长，最终导致肾功能丧失，但受影响患者的主要死亡原因是心血管疾病。血管功能障碍（内皮功能障碍和大弹性动脉僵硬）在疾病过程的早期就很明显，并且似乎涉及氧化应激和炎症的增加。患有 ADPKD 的成人预防 CVD 的治疗选择有限，因此儿童期可能是一个关键的治疗窗口。姜黄素是一种安全的天然多酚，存在于印度香料姜黄中，具有激活关键抗氧化剂转录、抑制炎症和减少增殖的独特能力。目标 1 将使用一项为期 1 年的随机、安慰剂对照、双盲试验，评估姜黄素（25 毫克/公斤/天）改善 ADPKD 儿童和年轻人（6-22 岁）血管功能的功效。目标 2 将利用最先进的质谱方法确定（在 18-22 岁的患者亚组中）改善是否与氧化应激和炎症减少相关。第三个探索性目标是使用 MRI 扫描评估肾脏总体积的变化。这项研究有可能建立一种新颖、安全且易于实施的疗法，用于治疗未充分研究的 ADPKD 儿童和年轻人群体中的动脉功能障碍，以及可能的肾囊性疾病。

项目成果

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial .

• DOI: 10.5414/cn109982
• 发表时间: 2020-07
• 期刊: Clinical nephrology
• 影响因子: 1.1
• 作者: Nowak KL;Chonchol M;Jovanovich A;You Z;Ambrosius WT;Cho ME;Glasser S;Lash J;Simmons DL;Taylor A;Weiner D;Rastogi A;Oparil S;Supiano MA
• 通讯作者: Supiano MA

Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.

• DOI: 10.34067/kid.0000962019
• 发表时间: 2020-06
• 期刊: Kidney360
• 作者: Nowak KL;Jovanovich A;Farmer-Bailey H;Bispham N;Struemph T;Malaczewski M;Wang W;Chonchol M
• 通讯作者: Chonchol M

Does inflammation affect outcomes in dialysis patients?

• DOI: 10.1111/sdi.12686
• 发表时间: 2018-07-01
• 期刊: SEMINARS IN DIALYSIS
• 影响因子: 1.6
• 作者: Nowak, Kristen L.;Chonchol, Michel
• 通讯作者: Chonchol, Michel