Lynn R. Willis

Renal Trauma and the Risk of Long-Term Complications in Shock Wave Lithotripsy

Open surgery for removal of upper urinary tract stones has long been associated with a high morbidity and mortality. So when shock wave (SW) lithotripsy (SWL) was introduced in the early 1980s, the climate was right for acceptance of a noninvasive method for stone comminution. The growth in popularity of SWL was extremely rapid, based in part on the perception that it was entirely safe [1]. Now, after a decade of clinical SWL, experience tells us differently. SWL may be very effective at breaking kidney stones, but it can also cause severe renal trauma that can lead to irreversible long-term complications [2, 3].

Kidney Damage and Renal Functional Changes are Minimized by Waveform Control that Suppresses Cavitation in Shock Wave Lithotripsy

PURPOSE In studies to understand better the role of cavitation in kidney trauma associated with shock wave lithotripsy we assessed structural and functional markers of kidney injury when animals were exposed to modified shock waves (pressure release reflector shock pulses) that suppress cavitation. Experiments were also performed in isolated red blood cells, an in vitro test system that is a sensitive indicator of cavitation mediated shock wave damage. MATERIALS AND METHODS We treated 6-week-old anesthetized pigs with shock wave lithotripsy using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia) fitted with its standard brass ellipsoidal reflector (rigid reflector) or with a pressure release reflector insert. The pressure release reflector transposes the compressive and tensile phases of the lithotriptor shock pulse without otherwise altering the positive pressure or negative pressure components of the shock wave. Thus, with the pressure release reflector the amplitude of the incident shock wave is not changed but cavitation in the acoustic field is stifled. The lower pole of the right kidney was treated with 2,000 shocks at 24 kV. Glomerular filtration rate, renal plasma flow and tubular extraction of para-aminohippurate were measured in the 2 kidneys 1 hour before and 1 and 4 hours after shock wave lithotripsy, followed by the removal of each kidney for morphological analysis. In vitro studies assessed shock wave induced lysis to red blood cells in response to rigid or pressure release reflector shock pulses. RESULTS Sham shock wave lithotripsy had no significant effect on kidney morphology, renal hemodynamics or para-aminohippurate extraction. Shock waves administered with the standard rigid reflector induced a characteristic morphological lesion and functional changes that included bilateral reduction in renal plasma flow, and unilateral reduction in the glomerular filtration rate and para-aminohippurate extraction. When the pressure release reflector was used, the morphological lesion was limited to hemorrhage of vasa recta vessels near the tips of renal papillae and the only change in kidney function was a decrease in the glomerular filtration rate at the 1 and 4-hour periods in shock wave treated kidneys. Red blood cell lysis in vitro was significantly lower with the pressure release reflector than with the rigid reflector. CONCLUSIONS These data demonstrate that shock wave lithotripsy damage to the kidney is reduced when cavitation is suppressed. This finding supports the idea that cavitation has a prominent role in shock wave lithotripsy trauma.

SHOCK WAVE LITHOTRIPSY-INDUCED RENAL INJURY

Both clinical and experimental reports clearly show that shock wave lithotripsy (SWL) causes acute renal effects in a majority, if not all, treated kidneys. SWL-induced acute renal damage may result in severe injury to the nephron, microvasculature, and the surrounding interstitium. In addition, at least three chronic adverse effects have been identified when shock waves are administered at a therapeutic dose. These include (1) an accelerated rise in arterial blood pressure, (2) a decrease in renal function, and (3) an increased rate of stone recurrence. The clinical and experimental data that document tissue injury as a result of shock wave treatment are compelling, but have not allowed us to determine the factors responsible for the adverse acute side effects or to identify conditions that may predispose a patient to serious long-term health problems. Thus, there is an urgent need for incisive, fundamental experimental studies to establish the safe limits for shock wave delivery. To accomplish this goal, animal experimentation is required so that the time course and severity of acute and chronic alterations can be followed in a model that closely mimics human renal structure and functions. The minipig provides this model.

Prevention of Lithotripsy-Induced Renal Injury by Pretreating Kidneys with Low-Energy Shock Waves

Lithotripsy shock waves (SW) to one renal pole damage that pole but protect the opposite pole from the damage inflicted by another, immediate application of SW. This study investigated whether the protection (1) occurs when the first treatment causes no injury, (2) is caused by SW or injury, (3) exhibits a threshold, and (4) occurs when the same pole receives both treatments. Six- to 7-wk-old anesthetized female pigs were studied. The following groups were studied: group 1 (n=4), 2000 SW at 12 kV to one pole and 2000 SW at 24 kV (standard) to the opposite pole; group 2 (n=6), same as group 1 except 500 12-kV SW pretreatment; group 3 (n=8), 500 12-kV, 2000 standard SW, all to the same pole; and group 4 (n=8), same as group 3 except 100 12-kV SW pretreatment. Mean+/-SD lesion size in group 1, first pole treated, was 0.66+/-0.82% of functional renal volume (FRV; P<0.05 versus 5.22+/-3.6% FRV with no pretreatment [NP]; 95% confidence interval [CI] -7.0 to -2.1) and 0.50+/-0.68% FRV in the opposite pole after 2000 standard SW (P<0.05 versus NP; 95% CI -9.4 to -0.08). Mean lesion size (first pole) in group 2 was 0.020+/-0.028% FRV (P<0.01 versus NP; 95% CI -9.2 to -1.2) and 0.43+/-0.54% FRV in the opposite pole after 2000 standard SW (P<0.05 versus NP; 95% CI -8.8 to -0.82). Same-pole SW (groups 3 and 4) also protected. Mean lesion sizes were 0.28+/-0.33% (P<0.01 versus NP; 95% CI -8.0 to -1.9) in group 3 and 0.39+/-0.48% FRV (P<0.01 versus NP; 95% CI -8.2 to -1.7) in group 4. It is concluded that the pretreatment protocol substantially limits the renal injury that normally is caused by SWL and occurs when the pretreatment and standard SW are applied to the same pole. The threshold for the protection may be <100 SW.

In Vivo Pressure Measurements of Lithotripsy Shock Waves in Pigs

Stone comminution and tissue damage in lithotripsy are sensitive to the acoustic field within the kidney, yet knowledge of shock waves in vivo is limited. We have made measurements of lithotripsy shock waves inside pigs with small hydrophones constructed of a 25-microm PVDF membrane stretched over a 21-mm diameter ring. A thin layer of silicone rubber was used to isolate the membrane electrically from pig fluid. A hydrophone was positioned around the pig kidney following a flank incision. Hydrophones were placed on either the anterior (shock wave entrance) or the posterior (shock wave exit) surface of the left kidney. Fluoroscopic imaging was used to orient the hydrophone perpendicular to the shock wave. For each pig, the voltage settings (12-24 kV) and the position of the shock wave focus within the kidney were varied. Waveforms measured within the pig had a shape very similar to those measured in water, but the peak pressure was about 70% of that in water. The focal region in vivo was 82 mm x 20 mm, larger than that measured in vitro (57 mm x 12 mm). It appeared that a combination of nonlinear effects and inhomogeneities in the tissue broadened the focus of the lithotripter. The shock rise time was on the order of 100 ns, substantially more than the rise time measured in water, and was attributed to higher absorption in tissue.

Quantitation of shock wave lithotripsy-induced lesion in small and large pig kidneys.

Shock wave lithotripsy (SWL) is known to cause injury to the kidney. However, it is not known how lesion size varies as the parameters of SWL treatment (number of shocks, kilovoltage, kidney size) are changed. This hypothesis could not be tested because there was no method available to quantitate accurately the SWL‐induced renal lesion.

Pretreatment with low-energy shock waves induces renal vasoconstriction during standard shock wave lithotripsy (SWL): a treatment protocol known to reduce SWL-induced renal injury.

To test the hypothesis that the pretreatment of the kidney with low‐energy shock waves (SWs) will induce renal vasoconstriction sooner than a standard clinical dose of high‐energy SWs, thus providing a potential mechanism by which the pretreatment SW lithotripsy (SWL) protocol reduces tissue injury.

Evidence for increased postprandial distal nephron calcium delivery in hypercalciuric stone-forming patients

A main mechanism of idiopathic hypercalciuria (IH) in calcium stone-forming patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption that cannot be explained by selective reduction of serum parathyroid hormone levels; the nephron site(s) responsible are not as yet defined. Using fourteen 1-h measurements of the clearances of sodium, calcium, and endogenous lithium during a three-meal day in the University of Chicago General Clinical Research Center, we found reduced postprandial proximal tubule reabsorption of sodium and calcium in IHSF vs. normal subjects. The increased distal sodium delivery is matched by increased distal reabsorption so that urine sodium excretions do not differ, but distal calcium reabsorption does not increase enough to match increased calcium delivery, so hypercalciuria results. In fact, urine calcium excretion and overall renal fractional calcium reabsorption both are high in IHSF vs. normal when adjusted for distal calcium delivery, strongly suggesting a distal as well as proximal reduction of calcium reabsorption. The combination of reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new finding and indicates that IH involves a complex, presumably genetic, variation of nephron function. The increased calcium delivery into the later nephron may play a role in stone formation via deposition of papillary interstitial apatite plaque.

Branching patterns of the renal artery of the pig

The pig kidney is similar in structure and function to the human kidney, thus making it a useful model in understanding the human kidney in health and disease. However, little is known about the branching pattern of the pig renal artery as compared with the human and other animals.

Potential for Cavitation-Mediated Tissue Damage in Shockwave Lithotripsy

PURPOSE Shockwave lithotripsy (SWL) injures renal tissue, and cavitation has been reported to mediate some of these effects. Much of the work characterizing the cavitation injury of SWL has been performed in small animals or in vitro. We describe experiments that promote cavitation during SWL and estimate the spatial distribution of the resulting hemorrhagic lesion in a large-animal (porcine) model of clinical lithotripsy. MATERIALS AND METHODS The lower pole calix of the left kidney in female farm pigs was targeted for SWL with a Dornier HM3 lithotripter. Intraventricular injections of polystyrene microspheres were made before and at intervals during lithotripsy to blanket systemic circulation with cavitation nuclei. Following SWL, the abdominal viscera were inspected and the kidneys were processed for morphologic analysis. RESULTS Extensive surface hemorrhage occurred over both the targeted and contralateral kidneys, along with widespread petechial hemorrhage over the spleen, intestines, and peritoneum. The targeted kidneys developed subcapsular hematomas. Histology revealed focal and diffuse damage to the targeted kidneys and vascular rupture in both kidneys with complete necrosis of the walls of intralobular arteries and veins. CONCLUSIONS These results demonstrate the potential for unfocused shockwaves to damage blood vessels outside the focal zone of the lithotripter when the vasculature is seeded with cavitation nuclei. The wide distribution of damage suggests that the acoustic field of a lithotripter delivers negative pressures that exceed the cavitation threshold far off the acoustic axis. The findings underscore that conditions permissive for cavitation can lead to dramatic sequelae during SWL.