Protection Against Acute and Chronic Adverse Effects in SWL

防止 SWL 中的急性和慢性不良反应

• 批准号: 7759397
• 负责人: Andrew Evan
• 金额: $ 71.31万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7759397
• 关键词: Acoustics; Acute; Adverse effects; Animals; Arteries; CHRM3 gene; Calcium Oxalate; Calculi; Chronic; Clinic; Clinical; Clinical Research; Development; Diabetes Mellitus; Dose; Duct (organ) structure; Family suidae; Follow-Up Studies; Generations; Glucose; Glucose tolerance test; Human; Immunohistochemistry; Impairment; Injury; Instruction; Ion Transport; Kidney; Kidney Calculi; Kidney Papilla; Lead; Left kidney; Limb structure; Lithotripsy; Long-Term Effects; Longitudinal Studies; Mediating; Metabolic syndrome; Modeling; Nephrons; Non-Insulin-Dependent Diabetes Mellitus; Pancreas; Papillary; Patients; Phenotype; Population; Process; Production; Property; Protocols documentation; Renal function; Research; Resistance; Right kidney; Risk Factors; Role; Safety; Severities; Shock; Structure; System; Tail; Testing; Thick; Tissues; Tubular formation; Urine; Work; blood glucose regulation; brushite; diabetic; early onset; functional disability; improved; injured; pressure; prevent; protective effect; response; time interval; tongue papilla; vasoconstriction

Studies conducted to date by Project 1 have characterized the acute renal injury and functional impairment caused by shock wave lithotripsy (SWL), with identification of potentially harmful risk factors for SWL and strategies to reduce acute tissue injury. The studies proposed in this PPG renewal will extend these results into the long-term effects of SWL. The Mayo clinic recently released information on a 19 year follow-up study on patients whose kidney stones were treated with SWL, the results of which raised concerns that SWL might be a risk factor for the onset of diabetes mellitus. We will use pig models ofthe pre-diabetic (metabolic syndrome) and diabetic (type 2 diabetes) phenotype and perform glucose regulation tests to determine whether SWL is indeed a risk factor for the onset, or increasing the severity, of diabetes mellitus; as well as investigate the influence of renal sidedness oftreatment and lithotripter type (Aim 1). Our research group has identified SWL protocols that protect the kidney from the injurous effects of shock waves, and we propose to determine the mechanism(s) by which these SWL protection procotols initiate their protective effect (Aims 2 and 3). Longitudinal studies have shown that patients are converting from calcium oxalate stone formers to brushite stone formers and that this is correlated with the number of SWL treatments. This is worrisome as brushite stones are hard stones that are difficult to fragment with SWL. A pig model will be used to test whether SWL-induced damage ofthe papilla results in long-term changes in nephron structure and function, leading to an impairment of papillary urine acidification and the production of a more alkaline urine, a milieu which would favor brushite stone formation; and to determine whether SWL protection protocols can prevent such adverse changes in renal structure and function (Aim 4). These aims have significant translational implications and will make SWL safer as they will identify what types of SWL treatments will lead to long-term adverse effects; optimize and determine the mechanisms of lithotripsy protocols that are protective from shock wave-induced injury, and the use of such SWL protection protocols to lessen/prevent the long-term complications of SWL. RELEVANCE (See instructions): Potential long-term adverse complications of SWL are becoming apparent in the stone forming population (e.g. diabetes, conversion to kidney stones that are resistant to SWL therapy). The proposed research will clarify whether SWL is responsible for these chronic adverse effects, and provide strategies to lessen and/or avoid such complications. These new observations will improve the safety of SWL for all patients.

迄今通过项目1进行的研究表征了急性肾脏损伤和功能障碍 由冲击波岩石疗法（SWL）引起，并确定了SWL和 减少急性组织损伤的策略。此PPG续订中提出的研究将把这些结果扩展到 SWL的长期影响。 梅奥诊所最近发布了有关肾结石的19年随访研究的信息 用SWL处理，结果提出了SWL可能是发作的危险因素 糖尿病。我们将使用糖尿病前（代谢综合征）和糖尿病（2型糖尿病）的猪模型 表型和执行葡萄糖调节测试，以确定SWL是否确实是发作的危险因素，还是 增加糖尿病的严重程度；以及研究肾脏方面的处理和 岩石磨牙类型（AIM 1）。我们的研究小组确定了保护肾脏免受的SWL方案 冲击波的损伤作用，我们建议确定这些SWL保护的机制 Procotols启动其保护作用（目标2和3）。纵向研究表明患者是 从草酸钙石材形成钙转化为刷石形成器，这与 SWL治疗的数量。这很令人担忧，因为刷石是硬石，很难与 SWL。猪模型将用于测试SWL诱导的乳头损伤是否会导致长期变化 肾单位的结构和功能，导致乳头状尿酸化损害，并产生A 更多的碱性尿液，一种偏爱刷石的环境；并确定SWL是否 保护协议可以防止肾脏结构和功能的不良变化（AIM 4）。 这些目标具有重大的翻译含义，并将使SWL更安全，因为它们将确定哪些类型 SWL治疗的长期不良影响；优化并确定岩性疗法的机制 免受冲击波引起的伤害的保护方案，并使用此类SWL保护方案 减少/防止SWL的长期并发症。 相关性（请参阅说明）： SWL的潜在长期不良并发症在石材形成人群中变得显而易见 （例如，糖尿病，转化为耐SWL治疗的肾结石）。拟议的研究将 澄清SWL是否负责这些慢性不良影响，并提供减少和/或 避免这种并发症。这些新观察结果将提高所有患者SWL的安全性。