Studies conducted to date by Project 1 have characterized the acute renal injury and functional impairment caused by shock wave lithotripsy (SWL), with identification of potentially harmful risk factors for SWL and strategies to reduce acute tissue injury. The studies proposed in this PPG renewal will extend these results into the long-term effects of SWL. The Mayo clinic recently released information on a 19 year follow-up study on patients whose kidney stones were treated with SWL, the results of which raised concerns that SWL might be a risk factor for the onset of diabetes mellitus. We will use pig models ofthe pre-diabetic (metabolic syndrome) and diabetic (type 2 diabetes) phenotype and perform glucose regulation tests to determine whether SWL is indeed a risk factor for the onset, or increasing the severity, of diabetes mellitus;as well as investigate the influence of renal sidedness oftreatment and lithotripter type (Aim 1). Our research group has identified SWL protocols that protect the kidney from the injurous effects of shock waves, and we propose to determine the mechanism(s) by which these SWL protection procotols initiate their protective effect (Aims 2 and 3). Longitudinal studies have shown that patients are converting from calcium oxalate stone formers to brushite stone formers and that this is correlated with the number of SWL treatments. This is worrisome as brushite stones are hard stones that are difficult to fragment with SWL. A pig model will be used to test whether SWL-induced damage ofthe papilla results in long-term changes in nephron structure and function, leading to an impairment of papillary urine acidification and the production of a more alkaline urine, a milieu which would favor brushite stone formation;and to determine whether SWL protection protocols can prevent such adverse changes in renal structure and function (Aim 4).
These aims have significant translational implications and will make SWL safer as they will identify what types of SWL treatments will lead to long-term adverse effects;optimize and determine the mechanisms of lithotripsy protocols that are protective from shock wave-induced injury, and the use of such SWL protection protocols to lessen/prevent the long-term complications of SWL.

Public Health Relevance

Potential long-term adverse complications of SWL are becoming apparent in the stone forming population (e.g. diabetes, conversion to kidney stones that are resistant to SWL therapy). The proposed research will clarify whether SWL is responsible for these chronic adverse effects, and provide strategies to lessen and/or avoid such complications. These new observations will improve the safety of SWL for all patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-R)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University-Purdue University at Indianapolis
United States
Zip Code
Janssen, Karmon M; Brand, Timothy C; Bailey, Michael R et al. (2018) Effect of Stone Size and Composition on Ultrasonic Propulsion Ex Vivo. Urology 111:225-229
Simon, Julianna C; Sapozhnikov, Oleg A; Kreider, Wayne et al. (2018) The role of trapped bubbles in kidney stone detection with the color Doppler ultrasound twinkling artifact. Phys Med Biol 63:025011
Matula, Thomas J; Sapozhnikov, Oleg A; Ostrovsky, Lev A et al. (2018) Ultrasound-based cell sorting with microbubbles: A feasibility study. J Acoust Soc Am 144:41
Williams Jr, James C; Borofsky, Michael S; Bledsoe, Sharon B et al. (2018) Papillary Ductal Plugging is a Mechanism for Early Stone Retention in Brushite Stone Disease. J Urol 199:186-192
Sapozhnikov, Oleg; Nikolaeva, Anastasiia; Bailey, Michael (2018) The effect of shear waves in an elastic sphere on the radiation force from a quasi-Gaussian beam. Proc Meet Acoust 32:
Zwaschka, Theresa A; Ahn, Justin S; Cunitz, Bryan W et al. (2018) Combined Burst Wave Lithotripsy and Ultrasonic Propulsion for Improved Urinary Stone Fragmentation. J Endourol 32:344-349
Connors, Bret A; Schaefer, Ray B; Gallagher, John J et al. (2018) Preliminary Report on Stone Breakage and Lesion Size Produced by a New Extracorporeal Electrohydraulic (Sparker Array) Discharge Device. Urology 116:213-217
Dai, Jessica C; Dunmire, Barbrina; Sternberg, Kevan M et al. (2018) Retrospective comparison of measured stone size and posterior acoustic shadow width in clinical ultrasound images. World J Urol 36:727-732
Rosnitskiy, Pavel B; Yuldashev, Petr V; Sapozhnikov, Oleg A et al. (2017) Design of HIFU Transducers for Generating Specified Nonlinear Ultrasound Fields. IEEE Trans Ultrason Ferroelectr Freq Control 64:374-390
Li, Guangyan; Connors, Bret A; Schaefer, Ray B et al. (2017) Evaluation of an experimental electrohydraulic discharge device for extracorporeal shock wave lithotripsy: Pressure field of sparker array. J Acoust Soc Am 142:3147

Showing the most recent 10 out of 267 publications