OPTIMIZING AN ESCALATING SHOCK WAVE AMPLITUDE TREATMENT STRATEGY TO PROTECT THE KIDNEY FROM INJURY DURING SHOCK WAVE LITHOTRIPSY

摘要

OBJECTIVE class="unordered" style="list-style-type:disc" id="L1">To test the idea that a pause (~3-min) in the delivery of shock waves (SW) soon after the initiation of treatment is unnecessary for achieving a reduction in renal injury, if treatment is begun at a low power setting that generates low-amplitude SWs.MATERIALS AND METHODS class="unordered" style="list-style-type:disc" id="L2">Anesthetized female pigs were assigned to one of three SWL treatment protocols that did not involve a pause in SW delivery of more than 10 seconds (2000 SWs at 24 kV; 100 SWs at 12 kV + ~10-sec pause + 2000 SWs at 24 kV; 500 SWs at 12 kV + ~10-sec pause + 2000 SWs at 24 kV; all SWs delivered at 120 SWs/min using an unmodified Dornier HM3 lithotripter).Renal function was measured before and after SWL.The kidneys were then processed for quantification of the SWL-induced hemorrhagic lesion. Values for lesion size were compared to previous data collected from pigs in which treatment included a 3-min pause in SW delivery.RESULTS class="unordered" style="list-style-type:disc" id="L3">All SWL treatment protocols produced a similar degree of vasoconstriction (23–41% reduction in GFR and ERPF) in the SW-treated kidney.The mean renal lesion in pigs treated with 100 low-amplitude SWs delivered before the main dose of 2000 high-amplitude SWs (2.27% FRV) was statistically similar to that measured for pigs treated with 2000 SWs all at high-amplitude (3.29% FRV). However, pigs treated with 500 low-amplitude SWs before the main SW dose had a significantly smaller lesion (0.44% FRV) that was comparable to the lesion in pigs from a previous study in which there was a 3-min pause in treatment separating a smaller initial dose of 100 low-amplitude SWs from the main dose of 2000 high-amplitude SWs (0.46% FRV). Time between the initiation of the low- and high-amplitude SWs was ~4-min for these latter two groups compared to ~1-min when there was negligible pause after the initial 100 low-amplitude SWs in the protocol.CONCLUSIONS class="unordered" style="list-style-type:disc" id="L4">Pig kidneys treated by SWL using a 2-step low-to-high power ramping protocol were protected from injury with negligible pause between steps, provided the time between the initiation of low-amplitude SWs and switching to high-amplitude SWs was ~4-min.Comparison with results from previous studies shows that protection can be achieved using various step-wise treatment scenarios in which either the initial dose of SWs is delivered at low-amplitude for ~4-min, or there is a definitive pause before resuming SW treatment at higher amplitude.Thus, we conclude that renal protection can be achieved without instituting a pause in SWL treatment. It remains prudent to consider that renal protection depends on the acoustic and temporal properties of SWs administered at the beginning stages of a SWL ramping protocol, and that this may differ according to the lithotripter at hand. class="kwd-title">Keywords: kidney, lithotripsy, swine, tissue injury class="head no_bottom_margin" id="S5title">INTRODUCTIONAn undesirable side effect of SWL treatment is that SWs can injure renal and surrounding tissue []. The primary acute lesion is vascular trauma with breakage of blood vessels and pooling of blood within the parenchyma, which if extending to the kidney surface will result in subcapsular or perirenal hematomas []. Along with the vascular insult, there is damage to tubules and the production and release of proinflammatory cytokines and injurious agents (e.g. iron/reactive oxygen metabolites; vasoconstrictor peptides/ischemia; metabolic toxins) that can result in fibrosis and the loss of functional tissue [,]. Such SW-induced injury has been linked to adverse outcomes such as hypertension, diabetes and exacerbation of kidney stone disease [–]. This raises concern about the long-term safety of SWL, and developing SWL treatment strategies that reduce or prevent tissue injury would certainly help mitigate such concerns.One approach to reduce SWL-induced tissue injury has been to alter the manner in which SWs are delivered to the kidney [,], and in this regard we have reported that treatment of the pig kidney with low-amplitude SWs followed by a 3-min pause in treatment prior to applying high-amplitude SWs will reduce SWL-induced hemorrhagic lesion sizes by as much as 20-fold []. In fact, similar protocols in which low-amplitude SWs were substituted with a relatively small number of higher-amplitude SWs were also shown to reduce SW-induced tissue damage, implicating the 3-min pause in treatment to be a critical factor in the development of the renal protective response [].On the other hand, some clinical centers begin SWL treatment at a low power setting to condition the patient to treatment-related discomfort and then gradually ramp up to higher levels with continuous delivery of SWs. That is, there is typically no pause in treatment during the lithotripsy session [–]. It is unclear even with power ramping if continuous delivery of SWs can be used to protect the kidney from injury. Therefore, we sought to determine in our pig model, using a 2-step ramping protocol, whether a definitive pause in SW delivery is needed in order to protect the kidney from SWL-related tissue damage.