Dual-head lithotripsy in synchronous mode: acute effect on renal function and morphology in the pig

OBJECTIVE: To assess the effect of dual-head lithotripsy on renal function and morphology in a pig model of shockwave (SW) injury, as lithotripters with two shock heads are now available for treating patients, but little information is available with which to judge the safety of treatment with dual pulses. MATERIALS AND METHODS: A dual-head electrohydraulic lithotripter (Duet, Direx Corp., Natick, MA, USA) was used to treat the lower renal pole of anaesthetized pigs with a clinical dose of SWs (2400 dual SWs; 10 kidneys) delivered in synchronous mode, i.e. both heads fired simultaneously. For comparison, pigs were treated with either 2400 SWs (12 kidneys) or 4800 SWs (eight) with a conventional electrohydraulic lithotripter (HM3, Dornier, Wessling, Germany). RESULTS: Dual-pulse SW treatment with the Duet lithotripter caused a decline in the mean (sd) glomerular filtration rate (GFR) of 4.1 (1.9) mL/min, with a trend for the effective renal plasma flow (RPF), at 31 (19) mL/min, to also decrease. These changes in renal haemodynamics were similar to the decreases in GFR and RPF in response to treatment with the HM3 lithotripter with 2400 SWs, at 4.8 (0.8) and 32 (10) mL/min, respectively, or 4800 SWs, at 5.4 (1.0) and 68 (14) mL/min, respectively. Linear association analysis showed that the functional response to dual-pulse SWs was more variable than with conventional SWs. Morphological quantification of kidney damage (expressed as a percentage of functional renal volume, FRV) showed that tissue injury with 2400 paired SWs with the Duet, at 0.96 (0.39)% FRV, was similar to injury produced by either 2400 single SWs, at 1.08 (0.38)% FRV, or 4800 single SWs, at 2.71 (1.02)% FRV, with the HM3. However, morphological damage was less consistent with the Duet (measurable in only five of eight kidneys) than that with the HM3 (measurable in all 12 kidneys). Acoustic output and the timing of dual SWs in synchronous mode increased in variability as the electrodes aged, affecting the amplitude and targeting of focal pressures. CONCLUSION: With the caveat that variability in the timing of dual SWs will unpredictably alter the distribution of SW energy within the kidney, this study shows that a clinical dose of dual-head SWs delivered in synchronous mode elicits a renal response similar to, but more variable than, that with a clinical dose of SWs from a conventional electrohydraulic lithotripter.     

Independent assessment of a wide-focus, low-pressure electromagnetic lithotripter: absence of renal bioeffects in the pig

OBJECTIVE

To assess the renal injury response in a pig model treated with a clinical dose of shock waves (SWs) delivered at a slow rate (27 SW/min) using a novel wide focal zone (18 mm), low acoustic pressure (<20 MPa) electromagnetic lithotripter (Xi Xin‐Eisenmenger, XX‐ES; Xi Xin Medical Instruments Co. Ltd., Suzhou, PRC).

MATERIALS AND METHODS

The left kidneys of anaesthetized female pigs were treated with 1500 SWs from either an unmodified electrohydraulic lithotripter (HM3, Dornier MedTech America, Inc., Kennesaw, GA, USA; 18 kV, 30 SW/min) or the XX‐ES (9.3 kV, 27 SW/min). Measures of renal function (glomerular filtration rate, GFR, and renal plasma flow) were collected before and after SW lithotripsy, and kidneys were harvested for histological quantification of vascular haemorrhage, expressed as a percentage of the functional renal volume (FRV). A fibre‐optic probe hydrophone was used to characterize the acoustic field, and the breakage of gypsum model stones was used to compare the function of the two lithotripters.

RESULTS

Kidneys treated with the XX‐ES showed no significant change in renal haemodynamic function and no detectable tissue injury. Pigs treated with the HM3 had a modest decline from baseline (≈ 20%) in both GFR (P > 0.05) and renal plasma flow (P = 0.064) in the treated kidney, but that was not significantly different from the control group. Although most HM3‐treated pigs showed no evidence of renal tissue injury, two had focal injury measuring 0.1% FRV, localized to the renal papillae. The width of the focal zone for the XX‐ES was ≈ 18 mm and that of the HM3 ≈ 8 mm. Peak positive pressures at settings used to treat pigs and break model stones were considerably lower for the XX‐ES (17 MPa at 9.3 kV) than for the HM3 (37 MPa at 18 kV). The XX‐ES required fewer SWs to break stones to completion than did the HM3, with a mean (sd ) of 634 (42) and 831 (43) SWs, respectively (P < 0.01). However, conditions were different for these tests because of differences in physical configuration of the two machines.

CONCLUSION

The absence of renal injury with the wide focal zone XX‐ES lithotripter operated at low shock pressure and a slow SW rate suggests that this lithotripter would be safe when used at the settings recommended for patient treatment. That the injury was also minimal using the Dornier HM3 lithotripter at a slow SW rate implies that the reduced tissue injury seen with these two machines was because they were operated at a slow SW rate. As recent studies have shown stone breakage to be improved when the focal zone is wider than the stone, a wide focal zone lithotripter operated at low pressure and slow rate has the features necessary to provide better stone breakage with less tissue injury.     

Renal injury during shock wave lithotripsy is significantly reduced by slowing the rate of shock wave delivery

OBJECTIVE: To assess the tissue protection afforded by simply reducing the rate of shock wave (SW) delivery, compared with studies in the pig in which SW lithotripsy (SWL)-induced vascular damage was significantly reduced by initiating treatment using low-amplitude SWs. MATERIALS AND METHODS: Juvenile pigs (6-7 weeks old) were treated with an unmodified lithotripter (HM3, Dornier Medical Systems, Kennesaw, GA) at either 120 or 30 SW/min. Treatment was to one kidney per pig, with SWs (2000, 24 kV) directed to a lower-pole calyx. After treatment, parenchymal haemorrhage was determined morphometrically and expressed as percentage of functional renal volume (%FRV). RESULTS: Kidneys treated at 120 SW/min had focal to extensive subcapsular haematomas. Parenchymal lesions were found only at the lower pole, but included regions within renal papillae and the cortex. Occasionally, damage extended across the full thickness of the kidney. The lesion in the pigs treated at 120 SW/min occupied a mean (sd) of 4.6 (1.7) %FRV. Kidneys of pigs treated at 30 SW/min showed no surface bleeding. Parenchymal haemorrhage was limited to papillae within the focal volume, and measured 0.08 (0.02) %FRV, a significant (P < 0.005) reduction in injury. CONCLUSIONS: Slowing the rate of delivery to 30 SW/min has a dramatic protective effect on the integrity of the kidney vasculature. This finding in our established pig model suggests a potential strategy to improve the safety of lithotripsy. As it was shown that a reduced SW rate also improves the efficiency of stone fragmentation, a slow rate appears to be a means to improve both the safety and efficacy of SWL.     

Effect of shock wave number on renal oxidative stress and inflammation

What’s known on the subject? and What does the study add? Oxidative stress and inflammation are tissue‐ and cell‐level components of shock wave lithotripsy (SWL)‐induced acute renal injury, which we recently showed to be localized principally to the medulla within the focal zone of the lithotripter. This study reports that the magnitude of the oxidative stress and inflammation observed in the medulla after SWL is dependent on the number of shock waves delivered to the kidney, indicating that this is a sensitive measure of renal injury caused by shock waves. OBJECTIVE To determine if the magnitude of the acute injury response to shock‐wave lithotripsy (SWL) depends on the number of SWs delivered to the kidney, as SWL causes acute renal oxidative stress and inflammation which are most severe in the portion of the kidney within the focal zone of the lithotripter. MATERIALS AND METHODS Pigs (7–8 weeks old) received 500, 1000 or 2000 SWs at 24 kV from a lithotripter to the lower pole calyx of one kidney. At 4 h after treatment the kidneys were removed, and samples of cortex and medulla were frozen for analysis of the cytokine, interleukin‐6, and for the stress response protein, heme oxygenase‐1 (HO‐1). Urine samples taken before and after treatment were analysed for the inflammatory cytokine, tumour necrosis factor‐α. For comparison, we included previously published cytokine data from pigs exposed to sham treatment. RESULTS Treatment with either 1000 or 2000 SWs caused a significant induction of HO‐1 in the renal medulla within the focal zone of the lithotripter (F2, 1000 SWs, P < 0.05; 2000 SWs, P < 0.001). Interleukin‐6 was also significantly elevated in the renal medulla of the pigs that received either 1000 or 2000 SWs (P < 0.05 and <0.001, respectively). Linear dose–response modelling showed a significant correlation between the HO‐1 and interleukin‐6 responses with SW dose (P < 0.001). Urinary excretion of tumour necrosis factor‐α from the lithotripsy‐treated kidney increased only for pigs that received 2000 SWs (P < 0.05). CONCLUSION The magnitude of renal oxidative stress and inflammatory response in the medulla increased with the number of SWs. However, it is not known if the HO‐1 response is beneficial or deleterious; determining that will inform us whether SWL‐induced renal injury can be assessed by quantifying markers of oxidative stress and inflammation.     

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

OBJECTIVE

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.

MATERIALS AND METHODS

Female farm pigs (6‐weeks‐old) were anaesthetized with isoflurane and the lower pole of the right kidney treated with SWs using a conventional electrohydraulic lithotripter (HM3, Dornier GmbH, Germany). Pulsed Doppler ultrasonography was used to measure renal resistive index (RI) in blood vessels as a measure of resistance/impedance to blood flow. RI was recorded from one intralobar artery located in the targeted pole of the kidney, and measurements taken from pigs given sham SW treatment (Group 1; no SWs, four pigs), a standard clinical dose of high‐energy SWs (Group 2; 2000 SWs, 24 kV, 120 SWs/min, seven pigs), low‐energy SW pretreatment followed by high‐energy SWL (Group 3; 500 SWs, 12 kV, 120 SWs/min + 2000 SWs, 24 kV, 120 SWs/min, eight pigs) and low‐energy SW pretreatment alone (Group 4; 500 SWs, 12 kV, 120 SWs/min, six pigs).

RESULTS

Baseline RI (≈0.61) was similar for all groups. Pigs receiving sham SW treatment (Group 1) had no significant change in RI. A standard clinical dose of high‐energy SWs (Group 2) did not significantly alter RI during treatment, but did increase RI at 45 min after SWL. Low‐energy SWs did not alter RI in Group 3 pigs, but subsequent treatment with a standard clinical dose of high‐energy SWs resulted in a significantly earlier (at 1000 SWs) and greater (two‐fold) rise in RI than that in Group 2 pigs. This rise in RI during the low/high‐energy SWL protocol was not due to a delayed vasoconstrictor response of pretreatment, as low‐energy SW treatment alone (Group 4) did not increase RI until 65 min after SWL.

CONCLUSIONS

The pretreatment protocol induces renal vasoconstriction during the period of SW application whereas the standard protocol shows vasoconstriction occurring after SWL. Thus, the earlier and greater rise in RI during the pretreatment protocol may be causally associated with a reduction in tissue injury.     

Extracorporeal shock wave lithotripsy at 60 shock waves/min reduces renal injury in a porcine model

OBJECTIVE

To determine if extracorporeal shock wave lithotripsy (ESWL) at 60 shock waves (SWs)/min reduces renal damage and haemodynamic impairment compared to treatment at 120 SWs/min.

MATERIALS AND METHODS

One kidney in each of 19 juvenile pigs (7–8 weeks old) was treated at 120 or at 60 SWs/min (2000 SWs, 24 kV) with an unmodified HM‐3 lithotripter (Dornier Medical Systems, Kennesaw, GA, USA). Renal function was determined before and after ESWL treatment by inulin clearance, extraction and clearance of para‐aminohippuric acid. Both kidneys were then removed to measure parenchymal lesion size by sectioning the entire kidney and quantifying the size of the haemorrhagic lesion in each slice.

RESULTS

ESWL at 60 SWs/min significantly reduced the size of the acute morphological lesion compared to 120 SWs/min (0.42% vs 3.93% of functional renal volume, P = 0.011) and blunted the decrease in glomerular filtration rate and renal plasma flow normally seen after treatment at 120 SWs/min.

CONCLUSIONS

Treatment at a firing rate of 60 SWs/min produces less morphological injury and causes less alteration in renal haemodynamics than treatment at 120 SWs/min in the pig model of ESWL‐induced renal injury.     

Shockwave lithotripsy: dose-related effects on renal structure, hemodynamics, and tubular function

BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) predictably damages renal tissue and transiently reduces function in both kidneys. This study characterized the effects on renal function of a supraclinical dose of shockwaves (SWs) (8000) in porcine kidneys and tested the hypothesis that such excessive treatment would intensify and prolong the resulting renal impairment. MATERIALS AND METHODS: Pigs aged 6 to 7 weeks were anesthetized and assigned to one of three groups. Groups 1 (N=8) and 2 (N=6) each received 8000 SWs at 24 kV (Dornier HM3) to the lower-pole calix of one kidney. Group 3 (7 pigs) received sham treatment. Renal function was monitored for the first 4 hours after SW treatment in Group 1 and for 24 hours in Group 2. Plasma renin activity was measured in Groups 2 and 3. RESULTS: The renal lesions produced by 8000 SWs comprised 13.8%+/-1.4% of the renal mass. In the 4-hour protocol, this injury was associated with marked reduction of the glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary sodium excretion in both kidneys, although fractional sodium excretion was reduced only in the shocked kidneys. In the 24-hour protocol, GFR and RPF remained below baseline in shocked kidneys at 24 hours. Evidence of progressive ischemic injury was noted in shocked tissue at 24 hours after SW treatment. CONCLUSIONS: These findings support the hypothesis that the severity of the renal injury caused by SWL is related to the number of SWs administered and demonstrate the connection in this relation between renal structure and function.     

Pretreatment with low-energy shock waves reduces the renal oxidative stress and inflammation caused by high-energy shock wave lithotripsy

The purpose of this study was to determine if pretreatment of porcine kidneys with low-energy shock waves (SWs) prior to delivery of a clinical dose of 2,000 SWs reduces or prevents shock wave lithotripsy (SWL)-induced acute oxidative stress and inflammation in the treated kidney. Pigs (7–8 weeks old) received 2,000 SWs at 24 kV (120 SW/min) with or without pretreatment with 100 SWs at 12 kV/2 Hz to the lower pole calyx of one kidney using the HM3. Four hours post-treatment, selected samples of renal tissue were frozen for analysis of cytokine, interleukin-6 (IL-6), and stress response protein, heme oxygenase-1 (HO-1). Urine samples were taken before and after treatment for analysis of tumor necrosis factor-α (TNF-α). Treatment with 2,000 SWs with or without pretreatment caused a statistically significant elevation of HO-1 and IL-6 in the renal medulla localized to the focal zone of the lithotripter. However, the increase in HO-1 and IL-6 was significantly reduced using the pretreatment protocol compared to no pretreatment. Urinary excretion of TNF-α increased significantly (p < 0.05) from baseline for pigs receiving 2,000 SWs alone; however, this effect was completely abolished with the pretreatment protocol. We conclude that pretreatment of the kidney with a low dose of low-energy SWs prior to delivery of a clinical dose of SWs reduces, but does not completely prevent, SWL-induced acute renal oxidative stress and inflammation.     

Shock wave lithotripsy of stones implanted in the proximal ureter of the pig

PURPOSE: Ureteral stones can be difficult to treat with shock wave (SW) lithotripsy. A strategy for lithotripsy of proximal ureteral stones is to push them back into the renal pelvis prior to administering SWs. However, push-back is invasive and not always possible. Since there are few clues to suggest how best to treat ureteral stones with SWs in situ, we developed an animal model for research on lithotripsy for ureteral stones. MATERIALS AND METHODS: Gypsum model stones were implanted bilaterally in the proximal ureter and renal calix of the pig via percutaneous access. Lithotripsy was performed using a HM3 lithotripter (Dornier Medical Systems, Marietta, Georgia) and stones at each location were treated with the same dose (400 SWs, 20 kV and 30 SWs per minute). Fragments were collected and the percent increase in projected surface area of the particles was determined. RESULTS: The breakage (mean percent area increase) of stones implanted in the proximal ureter was significantly less than that of stones located in the renal calix treated with the same dose of shock waves (134% vs 327%, p <0.001). Also, stones that were fully confined by the ureter did not break as well as stones located at the ureteropelvic junction. This indicates that the physical environment surrounding a stone can have a significant effect on the efficiency of SW action. CONCLUSIONS: The observation that stones implanted in the ureter showed decreased breakage compared with stones in the kidney is consistent with clinical experience. This finding is a valuable and even essential prerequisite for any experimental animal model system intended for the study of SW action in the breakage of ureteral stones.     

Effect of initial shock wave voltage on shock wave lithotripsy-induced lesion size during step-wise voltage ramping

OBJECTIVE

To determine if the starting voltage in a step‐wise ramping protocol for extracorporeal shock wave lithotripsy (SWL) alters the size of the renal lesion caused by the SWs.

MATERIALS AND METHODS

To address this question, one kidney from 19 juvenile pigs (aged 7–8 weeks) was treated in an unmodified Dornier HM‐3 lithotripter (Dornier Medical Systems, Kennesaw, GA, USA) with either 2000 SWs at 24 kV (standard clinical treatment, 120 SWs/min), 100 SWs at 18 kV followed by 2000 SWs at 24 kV or 100 SWs at 24 kV followed by 2000 SWs at 24 kV. The latter protocols included a 3–4 min interval, between the 100 SWs and the 2000 SWs, used to check the targeting of the focal zone. The kidneys were removed at the end of the experiment so that lesion size could be determined by sectioning the entire kidney and quantifying the amount of haemorrhage in each slice. The average parenchymal lesion for each pig was then determined and a group mean was calculated.

RESULTS

Kidneys that received the standard clinical treatment had a mean (sem ) lesion size of 3.93 (1.29)% functional renal volume (FRV). The mean lesion size for the 18 kV ramping group was 0.09 (0.01)% FRV, while lesion size for the 24 kV ramping group was 0.51 (0.14)% FRV. The lesion size for both of these groups was significantly smaller than the lesion size in the standard clinical treatment group.

CONCLUSIONS

The data suggest that initial voltage in a voltage‐ramping protocol does not correlate with renal damage. While voltage ramping does reduce injury when compared with SWL with no voltage ramping, starting at low or high voltage produces lesions of the same approximate size. Our findings also suggest that the interval between the initial shocks and the clinical dose of SWs, in our one‐step ramping protocol, is important for protecting the kidney against injury.     

Why stones break better at slow shockwave rates than at fast rates: in vitro study with a research electrohydraulic lithotripter

BACKGROUND AND PURPOSE: Stones break better when the rate of shockwave (SW) delivery is slowed. It has been hypothesized that the greater cavitation accompanying a fast rate shields pulse propagation, thus interfering with the delivery of SW energy to the stone. We tested this idea by correlating waveforms measured at the SW focus with cavitation viewed using high-speed imaging. MATERIALS AND METHODS: A series of U30 gypsum stones held in a 2-mm mesh basket were exposed to 200 SWs at 30 or 120 SW/min from a research electrohydraulic lithotripter (HM3 clone). Waveforms were collected using a fiberoptic probe hydrophone. High-speed imaging was used to observe cavitation bubbles in the water and at the stone surface. Results: Stone breakage was significantly better at 30 SW/min than at 120 SW/min. The rate had little effect on SW parameters in the water free field. In the presence of particulates released from stones, the positive pressure of the SW remained unaffected, but the trailing tensile phase of the pulse was significantly reduced at 120 SW/min. CONCLUSIONS: Cavitation bubbles do not persist between SWs. Thus, mature bubbles from one pulse do not interfere with the next pulse, even at 120 SW/min. However, cavitation nuclei carried by fine particles released from stones can persist between pulses. These nuclei have little effect on the compressive wave but seed cavitation under the influence of the tensile wave. Bubble growth draws energy from the negative-pressure phase of the SW, reducing its amplitude. This likely affects the dynamics of cavitation bubble clusters at the stone surface, reducing the effectiveness of bubble action in stone comminution.     

Percutaneous stone implantation in the pig kidney: a new animal model for lithotripsy research

PURPOSE: This report describes a new animal model for research on the parameters of shockwave delivery and the mechanisms of shockwave action in SWL. MATERIALS AND METHODS: Female pigs (approximately 45 kg) were anesthetized for creation of an upper pole peripheral caliceal access. The tract was dilated with a 30F Nephromax balloon and Amplatz sheath, and a 24F rigid nephroscope was used to guide a gypsum artificial stone into a lower pole calix. An internal ureteral stent was then placed. After a 2-hour recovery period, lithotripsy was performed using an unmodified Dornier HM3 lithotripter. Following SWL, en bloc excision of the urinary tract was performed, and the stone fragments were collected. RESULTS: As observed by nephroscopy, most stones were surrounded by urine that was free of clot or debris. Urine output was >1 mL/kg per minute by the time the animal was positioned for SWL after a 2-hour observation period. When the conditions of shockwave (SW) exposure were 400 SWs, 20 kV, and 120 SW/min, the efficiency of stone fragment recovery was 85% +/- 2% (N = 6 stones). CONCLUSIONS: This procedure provides a minimally invasive method for placement of model stones of clinically relevant size within the pig kidney. Stone implantation is efficient and permits experiments to be conducted in 1 day. Stone fragmentation can be quantitated, and the animal can serve as its own control. Long-term experiments are also feasible. Overall, this new animal model is appropriate for experimentation on the parameters of SW delivery in SWL.     

Calcium stone fragility is predicted by helical CT attenuation values

BACKGROUND AND PURPOSE: Helical CT has become the preferred method for imaging urinary calculi, and so it would be useful if data from helical CT could also be used to predict the number of shockwaves (SWs) needed to break a given stone. METHODS AND MATERIALS: We measured the number of SWs required to comminute calcium stones in vitro. RESULTS: The SW requirement correlated with stone size (volume, weight, diameter) and with helical CT attenuation values when the scans were performed at 3-mm collimation. When CT scans were performed at 1-mm collimation, the number of SWs needed for comminution did not correlate with helical CT attenuation values. This result indicates that the correlation with 3-mm scans was attributable to volume-averaging effects, in which smaller stones yield smaller attenuation values. That is, attenuation values from helical CT at larger beam collimation widths contain information about stone size that can be exploited to predict the fragility of calcium stones. We observed that for calcium stones, the number of SWs to comminution was generally less than half the stone CT attenuation value in Hounsfield units. This "half-attenuation rule" predicted the number of SWs needed to complete fragmentation for 95% of calcium stones (24/24 calcium oxalate monohydrate, 13/13 hydroxyapatite, 8/10 brushite stones). CONCLUSION: This in vitro study suggests that it may be possible to predict effective SW dose using helical CT prior to lithotripsy.     

Renal disease potentiates the injury caused by SWL

PURPOSE: The present study tested the hypothesis that renal disease potentiates the structural/functional changes induced by a clinical dose of shockwaves. MATERIALS AND METHODS: Experimental pyelonephritis was induced in 6- to 8-week-old pigs before treatment with 2,000 shocks at 24 kV. These pigs were divided into two groups according to whether they were infected with a highly virulent (Group 1) or less virulent (Group 2) inoculation of E. coli. All animals were imaged by MR prior to SWL as a means of documenting the extent of pyelonephritis and immediately after SWL to examine the lesion produced by the shockwaves. The glomerular filtration rate (GFR), renal plasma flow (RPF) and para-aminohippurate (PAH) extraction were determined bilaterally on day 30 (Group 1) or day 80 (Group 2). RESULTS: In group 2, urine flow and sodium excretion were reduced by 50% from baseline in the shocked kidneys at both 1 and 4 hours post-SWL. A sustained reduction in RPF through 4 hours post-SWL was noted in the shocked kidneys in Group 1, but RPF was significantly reduced only at the 1-hour determination in Group 2. Large, consistent reductions in GFR were evident at 1 and 4 hours post-SWL in shocked and unshocked kidneys of Group 2 and in the shocked kidneys of Group 1. No significant changes were noted in PAH extraction. CONCLUSION: Acute pyelonephritis exaggerated the effect of a clinical dose of shockwaves on renal hemodynamics. This effect suggests that renal disease may be risk factor for SWL-induced injury.     

Ultracal-30 gypsum artificial stones for research on the mechanisms of stone breakage in shock wave lithotripsy

Artificial stones are used in research on the mechanisms of stone breakage in shock wave lithotripsy (SWL) and in assessing lithotripter performance. We have adopted Ultracal-30 gypsum as a model, finding it suitable for SWL studies in vitro, acute animal experiments in which stones are implanted in the kidney, and as a target to compare the in vitro performance of intracorporeal lithotripters. Here we describe the preparation of U-30 stones, their material properties, shock wave (SW) breakage characteristics, and methods used for quantitation of stone fragmentation with this model. Ultracal-30 gypsum cement was mixed 1:1 with water, cast in plastic multi-well plates, then, the stones were liberated by dissolving the plastic with chloroform and stored under water. Stone breakage in SWL was assessed by several methods including measures of the increase in projected surface area of SW-treated stones. Breakage of hydrated stones showed a linear increase in fragment area with increased SW-number and SW-voltage. Stones stored in water for an extended time showed reduced fragility. Dried stones could be rehydrated so that breakage was not different from stones that had never been dry, but stones rehydrated for less than 96 h showed increased fragility to SWs. The physical properties of U-30 stones place them in the range reported for natural stones. U-30 stones in vitro and in vivo showed equivalent response to SW-rate, with ~200% greater fragmentation at 30 SW/min compared to 120 SW/min, suggesting that the mechanisms of SW action are similar under both conditions. U-30 stones provide a convenient, reproducible model for SWL research.     

Causes and consequences of kidney loss in patients with nephrolithiasis

BACKGROUND: It is unknown whether stone formers may safely donate a kidney. Nephrectomy could accelerate stone formation, or loss of filtration with age. We contrast, here, the course of stone patients with two versus one kidney. METHODS: One hundred fifteen patients with a single functioning kidney were compared with 3151 patients with two kidneys. Cause of kidney loss was determined, along with stone types, rates of stone formation, urine stone risk factors, and creatinine clearance. RESULTS: Women were 49.6% of the patients with kidney loss, compared to 33.6% of ordinary stone formers. Obstruction, stone burden, and infection were the most common reasons for kidney loss. We found an increased number of struvite and calcium phosphate stones among single kidney patients. Before and during treatment, single kidney patients had fewer stones than ordinary stone formers. Creatinine clearance was lower in the single kidney patients; rate of loss of kidney function with age was higher among single kidney males versus two kidney males if all patients are considered. Among males >age 45 years, the difference disappears. Females with one and two kidneys lost function with age at equivalent rates. Compared with nonstone formers, male stone formers lose kidney function with age at an accelerated rate. CONCLUSION: Nephrectomy does not worsen stone disease. It may increase loss of renal function among younger males. The pattern of renal function loss with age differs between stone formers and nonstone formers.     

In-Vivo relation between CT attenuation value and shockwave fragmentation

PURPOSE: To use CT attenuation numbers as a means of determining the susceptibility of an artificial stone to in-vivo fragmentation with extracorporeal shockwave lithotripsy (SWL). MATERIALS AND METHODS: Four types of artificial kidney stones having different CT attenuation values were used. One randomly selected stone was implanted in the renal pelvis of a kidney of 12 young pigs and exposed in vivo to 2500 shockwaves (21 kV) using an electrohydraulic lithotripter. Bilateral nephrectomy was performed after SWL. Fragments were strained through a mesh with a 3.1-mm grid, and the debris left on the mesh was dried and weighed. Fragmentation coefficients (FCs) were associated with CT attenuation values using a statistical model. RESULTS: The relation between FC and CT number was significant, indicating that as CT attenuation increases, FC is reduced. Larger stone fragments were obtained from stones with higher CT numbers. Initial stone weight was not a significant explanation for variations in FC. CONCLUSION: The CT values could be helpful in selecting patients for SWL in the future. However, other parameters such as stone porosity, shape, and roughness also will have to be considered.     

A new electromagnetic shock-wave generator “SLX-F2” with user-selectable dual focus size: ex vivo evaluation of renal injury

Storz Medical AG (Kreutzlingen/Switzerland) has developed a new electromagnetic shockwave (SW) generator, the “SLX-F2”, which allows the user to choose between a small-focus, high-pressure treatment regime or a wide-focus, low-pressure option. The aim of this study was to investigate, under standardized conditions, the impact of these two different treatment regimes on SW-induced renal injury. SW-induced renal injury was investigated by using the standardized model of the perfused ex vivo kidney. SWs were applied under ultrasound control in the parenchyma of a kidney pole. Different SW numbers (20, 50, 125, 250, 500, 1,000) were applied in three groups: group A was treated with a wider focus (80 MPa), groups B (60 MPa) and C (120 MPa) with a smaller focus (each parameter setting was repeated ten-fold). Disintegration capacity (measured by crater volume in cubes of plaster of Paris) was the same in groups A and C. After SW exposure, barium sulphate suspension was perfused through the renal artery. The maximum diameter (mm) of the extravasation in the cortex, representing the extent of vascular injury, was measured on X-ray mammography films. H&E staining was performed. In all three groups (A, B, C) a higher number of SWs caused the diameter of the extravasate to increase, with statistical significance appearing at 1,000 shots versus 20 shots (p < 0.05). Vascular injury was not influenced by the focal size and positive peak pressure at identical SW numbers applied. Histology of the focal area showed gap-like defects. Our ex vivo data show that renal vascular injury is independent of the focal diameter of the SW generator at the same peak positive pressure and disintegration power. This confirms the in vivo findings that show renal injury caused by SW as being related to the number of SWs administered. Clinical studies are needed to investigate whether there is any advantage to offering both treatment regimes in one SW machine—for example, by using the “wide-focus, low-pressure” option for kidney stones and the “small-focus, high-pressure” regimen for stones in the ureter. The renal injury caused by either regime remains comparable.     

Bilateral native nephrectomy improves renal isograft function in rats

Bilateral native nephrectomy has been suggested to improve renal allograft survival in man. This effect may be most prominent in patients experiencing acute tubular necrosis following transplantation. Thus, native kidneys may alter the course of ischemic acute tubular necrosis in the transplanted kidney. In the present studies, we utilized an experimental model of syngeneic transplantation in which rejection does not occur. We studied Lewis rat renal isografts transplanted into littermates following sham, unilateral or bilateral native nephrectomy. In a fourth group of rats, we evaluated the importance of native kidney excretory function by studying isografts transplanted into littermates with bilaterally obstructed native kidneys. Renal blood flow and excretory function were measured in vivo, eight days following transplantation. Renal excretory function of isografts transplanted into animals following bilateral native nephrectomy was similar to normal nontransplanted Lewis kidneys. The presence of either one or both functioning native kidneys significantly reduced isograft inulin clearance, PAH clearance, and blood flow. However, when isografts were transplanted into Lewis rats with bilaterally obstructed native kidneys, renal isograft inulin clearance and blood flow were not significantly impaired. Nontransplanted kidneys demonstrated "functional hypertrophy" following contralateral nephrectomy, with glomerular filtration rate and renal blood flow increasing by approximately 50%. In contrast, isograft glomerular filtration rate in animals following bilateral native nephrectomy was equivalent to that of single kidneys from normal animals with both kidneys in situ. However, renal blood flow of isografts from these animals increased to the same level as nontransplanted Lewis kidneys following contralateral nephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)