Risk for Renal Injury Caused by Shock Wave Lithotripsy

描述(申请人提供)：我们已经证明，临床剂量的冲击波(SWS)应用于一个肾脏的下极肾盏，作为冲击波碎石术(SWL)会导致可预测的大小和成分的损害，减少双肾的肾脏血流量，并产生与危险因素相关的肾脏反应。这些风险因素包括输入能量(千伏)、SWS、肾脏大小、接受SWS的次数、先前存在的肾脏炎症或疾病，以及在同一治疗过程中应用于同一肾脏的SWS。由于较新的第三代碎石机在碎石方面的效率较低，而且似乎比Donrier HM3碎石机更容易造成不良影响，因此拟议的研究将扩大我们现有的重点，包括对新的和新兴的碎石机的研究。这类研究的目标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。目标1和目标2将1)加强和完善我们目前对SWS所致肾脏损伤机制的看法，2)确定肾脏血管收缩在最小化SWS造成的肾脏损伤中的可能作用，以及3)确定在SWL期间预防氧化应激在多大程度上可以最大限度地减少或防止SWS引起的急性和/或慢性损害。AIMS 3和AIMS 4将重点关注SWL的几个新风险因素。这些因素包括可能会恶化或减轻冲击波损伤的肾组织出血倾向的条件、SWS的给药参数以及SWS本身的特征。我们还将评估第三代碎石机DiREx紧凑型Delta碎石机，它具有紧密的焦域和高入射压力，以及SWL的一项新兴技术，双头碎石机Duet by Direct，它们可能导致肾损伤和肾功能损害。所有这些拟议的研究都旨在了解冲击波的不利影响，并在SWL不良反应报告不断增加的情况下提高所有结石患者的安全性。

DESCRIPTION (provided by applicant): We have demonstrated that a clinical dose of shock waves (SWs) applied to the lower pole calyx of one kidney as shock wave lithotripsy (SWL) induces a lesion of predictable size and composition, 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 input energy (kilovolt), the SWs, kidney size, number of SWs administered, pre-existing renal inflammation or disease, and SWs applied to both the same kidney during the same treatment session. Since the newer 3rd-generation lithotripters are less effective at breaking stones and appear to be more prone to cause adverse effects than the Donrier HM3 lithotripter, the proposed studies 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. Aims 1 and 2 will 1) enhance and refine our current view of mechanisms for SW-induced renal injury, 2) determine the possible role of renal vasoconstriction in minimizing the renal trauma caused by SWs, and 3) determine the extent to which prevention of oxidative stress during SWL may minimize or prevent the acute and/or chronic lesions caused by SWs. Aims 3 and 4 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, parameters for administration of SWs, and characteristics of the SW, itself. We will also assess a 3rd-generation lithotripter, the Direx Compact Delta, which tight focal zone and high incident pressure, and an emerging technology in SWL, a twin-head lithotripter, the Duet by Direct their potential to cause renal trauma and impair renal function. All of these proposed studies aim at understanding the adverse effects of shock waves and advancing the safety of all stone patients at a time when reports of adverse effects in SWL are on the rise.