Progression of hemorrhagic kidney injury from burst wave lithotripsy exposures

Abstract

Burst wave lithotripsy (BWL) is a new non-invasive treatment for comminuting kidney stones. Although exposure parameters used in current clinical trials have produced negligible renal injury in preclinical pig studies, it remains of interest to understand how quickly injury accumulates, should it occur. BWL treatments lasting ≤30 min were delivered to 36 sites in 20 kidneys of 11 pigs. Treatments at 350 kHz utilized pulses with supra-clinical 8–9 MPa peak negative pressure, 20 cycles/pulse, and a pulse repetition frequency (PRF) of 10 or 40 Hz. Real-time monitoring was performed with B-mode and Doppler ultrasound to identify the presence and duration of cavitation activity, which has been correlated with the onset of injury. After treatment, kidneys were excised for magnetic resonance imaging (MRI) within 3 h of euthanasia. MRI was used to quantify the volume of any hemorrhagic injury. For sites with injury at 40 Hz PRF, the average (n = 5) injury volume increased with the number of BWL pulses (72, 720, 7200, or 72 000 pulses) delivered with cavitation. Notably, the rate of lesion growth slowed above 7200 pulses while all lesion volumes were smaller for equivalent cavitation exposures at 10 Hz PRF. [Funding support by NIH P01-DK043881, K01-DK104854.]