RISK FACTORS FOR SWL-INDUCED INJURY

在我们之前的资助期间，我们发现应用于一个肾脏下极肾盏的临床剂量的冲击波在F2处诱导可预测的病变，减少两个肾脏的肾血流量，并产生严重程度与风险因素相关的肾脏反应。这些风险因素包括千伏、肾脏大小、给予的冲击波数量、预先存在的肾脏炎症或疾病，以及在同一治疗期间对同一肾脏的两极施加的冲击波。由于已知较新的第3代碎石机碎石效果较差，并且似乎比Dornier HM 3碎石机更容易引起不良反应，因此本次更新申请将扩大我们现有的重点，以包括对新型和新兴碎石机的研究。这些研究的目的是开发新的治疗策略和技术，有可能提高所有碎石机的疗效和安全性。 在目标1中，项目1将确定SWL诱导的肾血管收缩的时间过程和机制。我们将为此目的与项目3互动。目标2将重点关注SWL的几个新的风险因素。这些因素包括可能预期会恶化或减轻在被冲击波损伤的肾组织中发生出血的趋势的状况（例如，高或低血压）和SW给药的参数（例如，脉冲重复率）。我们将为此目的与项目2互动。目的3将空化与血管病变相关联，以确定空化是否是细胞损伤的主要机制。我们将为此目的与项目3和4互动。目的4将描述低能量冲击波预处理保护肾脏免受高能量冲击波诱导的血管损伤的机制。可以想象，我们的预处理方案可以预防临床剂量的冲击波引起的大部分细胞损伤，从而减少患者的任何长期肾脏并发症，特别是那些接受多次治疗的患者。我们将为此目的与项目2互动。目标5将评估第三代碎石机（例如，紧凑型Delta，具有紧凑的聚焦区和高入射压力）和新兴技术的SWL（双头碎石机，Direx“Duet”），因为它们可能导致肾损伤和肾功能损害。我们将与项目2和项目3互动，以实现这一目标。 所有这些拟议的研究旨在了解SWs的不良反应，并在SWL不良反应报告不断增加的情况下，提高SWL对所有结石患者的安全性。

During our previous funding period we showed that a clinical dose of shock waves applied to the lower pole calyx of one kidney induces a predictable lesion at F2, reduces renal blood flow in both kidneys, and produces a renal response the severity of which is related to risk factors. These risk factors include kilovoltage, kidney size, number of shock waves administered, pre-existing renal inflammation or disease, and shock waves applied to both poles of the same kidney during the same treatment session. Since the newer 3rd-generation lithotripters are known to be less effective at breaking stones and appear to be more prone to cause adverse effects than the Dornier HM3 lithotripter, this renewal application will expand our existing focus to include studies of the new and emerging lithotripters. The goal of such studies is to develop new treatment strategies and technologies with the potential to improve the efficacy and safety of all lithotripters. In Aim 1, Project 1 will determine the time-course and mechanism of SWL-induced renal vasoconstriction. We will interact with Project 3 for this Aim. Aim 2 will focus on several new risk factors for SWL. These factors include conditions that might be expected to worsen or lessen the tendency for bleeding to occur in renal tissue damaged by shock waves (e.g., high or low blood pressure) and parameters for administration of SWs (e.g., pulse repetition rate). We will interact with Project 2 for this Aim. Aim 3 will correlate cavitation with the vascular lesions to determine if cavitation is the primary mechanism of cell injury. We will interact with Projects 3 & 4 for this Aim. Aim 4 will characterize the mechanism whereby pretreatment with low-energy shock waves protects the kidney form vascular damage induced by high-energy shock waves. It is conceivable that most of the cellular damage induced by a clinical dose of shock wave can be prevented by our pretreatment protocol, thereby, reducing any long-term renal complications for the patient, especially those receiving multiple treatments. We will interact with Project 2 for this Aim. Aim 5 will assess a 3rd generation lithotripter (e.g., Compact Delta that has a tight-focal-zone and high-incident-pressure) and an emerging technology in SWL (twin head lithotripter, the Direx "Duet") for their potential to cause renal trauma and impair renal function. We will interact with Projects 2 and 3 for this Aim. All of these proposed studies aim at understanding the adverse effects of SWs and advancing the safety of SWL for all stone patients at a time when reports of adverse effects in SWL are on the rise.