Risk for Renal Injury Caused by Shock Wave Lithotripsy

描述（由申请人提供）：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（SWL），可诱导可预测大小和组成的病变，减少两个肾脏的肾血流量，并产生肾脏反应，其严重程度与危险因素有关。这些风险因素包括输入能量（千伏）、SWs、肾脏大小、SWs给药数量、先前存在的肾脏炎症或疾病，以及在同一治疗期间对同一肾脏施加的SWs。由于较新的第三代碎石机在碎石方面的效果较差，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，包括对新型和新兴碎石机的研究。这些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。目的1和2将1)加强和完善我们目前对sw诱导肾损伤机制的看法，2)确定肾血管收缩在减少sw引起的肾损伤中的可能作用，以及3)确定在SWL期间预防氧化应激在多大程度上可以减轻或预防sw引起的急性和/或慢性病变。目标3和目标4将重点关注SWL的几个新的风险因素。这些因素包括可能会加重或减少因冲击波损伤的肾组织出血倾向的条件、SW给药的参数以及SW本身的特征。我们还将评估第三代碎石机，Direx Compact Delta，它具有紧密的焦点区域和高入射压力，以及SWL的新兴技术，双头碎石机，Duet by Direct，它们可能导致肾脏损伤和损害肾功能。在SWL不良反应报道不断增加的背景下，所有这些拟议的研究都旨在了解冲击波的不良反应，并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.