In Situ Kidney Insonation With Microbubble Contrast Agents Does Not Cause Renal Tissue Damage in a Porcine Model

Jiménez, Carlos; Gracia, Raquel de; Aguilera, Alfredo; Alonso, Sergio; Cirugeda, A; Benito, Javier; Regojo, Rita María; Aguilar, R.; Warlters, Andrea; Gómez, Rosa; Largo, Carlota; Selgas, Rafael

doi:10.7863/jum.2008.27.11.1607

Cited by 26 publications

(24 citation statements)

References 16 publications

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“…Subsequent studies have been performed in rat (13,31,41), rabbit (59), dog (63,64,68), swine (24,69), mouse (55,57), and isolated organs (54). Contrast ultrasound imaging of the kidney is not in widespread clinical use, although studies have demonstrated potential utility for evaluation of focal abnormalities (46) and in identifying rejection following renal transplant (14,27,28).…”

Section: Discussionmentioning

confidence: 99%

Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging

Declèves

Rychak

Smith

et al. 2013

American Journal of Physiology-Renal Physiology

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Declèves AE, Rychak JJ, Smith DJ, Sharma K. Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging. Am J Physiol Renal Physiol 305: F1343-F1351, 2013. First published September 18, 2013 doi:10.1152/ajprenal.00326.2013.-Obesity-related kidney disease occurs as a result of complex interactions between metabolic and hemodynamic effects. Changes in microvascular perfusion may play a major role in kidney disease; however, these changes are difficult to assess in vivo. Here, we used perfusion ultrasound imaging to evaluate cortical blood flow in a mouse model of high-fat diet-induced kidney disease. C57BL/6J mice were randomized to a standard diet (STD) or a high-fat diet (HFD) for 30 wk and then treated either with losartan or a placebo for an additional 6 wk. Noninvasive ultrasound perfusion imaging of the kidney was performed during infusion of a microbubble contrast agent. Blood flow within the microvasculature of the renal cortex and medulla was derived from imaging data. An increase in the time required to achieve full cortical perfusion was observed for HFD mice relative to STD. This was reversed following treatment with losartan. These data were concurrent with an increased glomerular filtration rate in HFD mice compared with STD-or HFD-losartan-treated mice. Losartan treatment also abrogated fibro-inflammatory disease, assessed by markers at the protein and messenger level. Finally, a reduction in capillary density was found in HFD mice, and this was reversed upon losartan treatment. This suggests that alterations in vascular density may be responsible for the elevated perfusion time observed by imaging. These data demonstrate that ultrasound contrast imaging is a robust and sensitive method for evaluating changes in renal microvascular perfusion and that cortical perfusion time may be a useful parameter for evaluating obesity-related renal disease. ultrasound contrast imaging; obesity-related kidney disease; renal perfusion THE GROWING EPIDEMIC OF OBESITY is a serious health and economic burden throughout the world. The consequence of obesity over time is characterized by insulin resistance, hyperglycemia, atherosclerosis, dyslipidemia, and hypertension. This cluster of risk factors referred to as metabolic syndrome occurs with 50% prevalence in patients 50-to 60-yr-old (4) and contributes to cardiovascular disease. Obesity is a major risk factor for diabetes and hypertension, which together account for ϳ70% of all cases of end-stage renal disease (6). However, there is growing evidence suggesting that obesity by itself may be an independent risk factor for the development of vascular dysfunction and renal disease (21,44,66). Obesity-related kidney disease occurs as a result of complex interactions between metabolic and hemodynamic factors and is characterized by changes of renal perfusion, vascular dysfunction, as well as albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis (20,37,48,50). Alterations in blood flow within the cortex or the medulla ma...

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Section: Discussionmentioning

confidence: 99%

Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging

Declèves

Rychak

Smith

et al. 2013

American Journal of Physiology-Renal Physiology

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“…Some concerns have been raised about the safety of this procedure. Jiménez and colleagues [28] showed in a porcine model that repeated insonification of the kidney at high MI did not produce any histological change either immediately after the procedure or 4 hours later. There were no signs of inflammatory response and no signs of extravasation of erythrocytes from the capillary system.…”

Section: Contrast-enhanced Ultrasoundmentioning

confidence: 99%

Bench-to-bedside review: Contrast enhanced ultrasonography - a promising technique to assess renal perfusion in the ICU

et al. 2011

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Acute kidney injury (AKI) is common in critically ill patients and associated with important morbidity and mortality. Although alterations in renal perfusion are thought to play a causative role in the pathogenesis of AKI, there is, to date, no reliable technique that allows the assessment of renal perfusion that is applicable in the ICU. Contrast-enhanced ultrasound (CEUS) is an ultrasound imaging technique that makes use of microbubble-based contrast agents. These microbubbles, when injected into the bloodstream, allow visualization of vascular structures and, with contrast-specific imaging modes, detection of blood flow at the capillary level. Some recent CEUS-derived approaches allow quantification of blood flow in several organs, including the kidney. Current generation ultrasound contrast agents have strong stability and safety profiles. Along with post-marketing surveillance, numerous studies report safe administration of these agents, including in critically ill patients. This review presents information on the physical principles underlying CEUS, the methods allowing blood flow quantification and the potential applications of CEUS in critical care nephrology, currently as a research tool but perhaps in the future as a way of monitoring renal perfusion.

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“…The rationale for contact scanning of the kidney was not clear, particularly since the method does not allow clear imaging of the proximal cortex for normal settings of the focal zone depth. No visual or histological evidence of GCH in the proximal cortex or other renal tissue damage was found in this porcine model of CEDUS [7]. These contradictory results for rats and pigs are puzzling and worthy of further investigation.…”

Section: Introductionmentioning

confidence: 90%

“…This present study was undertaken to assess possible renal tissue damage in pigs using methods which replicated, as much as possible, the methods which would be used in humans. In addition, methods similar to those of Jimenez et al [7] were tested in order to understand the origin of the contradictory results.…”

Section: Introductionmentioning

confidence: 99%

Contrast-Enhanced Diagnostic Ultrasound Causes Renal Tissue Damage in a Porcine Model

Miller

Dou

Wiggins

2010

Journal of Ultrasound in Medicine

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Objective Glomerular capillary hemorrhage (GCH) has been reported and confirmed as a consequence of contrast-enhanced diagnostic ultrasound (CEDUS) of rat kidney. This study assessed renal tissue injury in the larger porcine model. Methods The right kidneys of anesthetized pigs were imaged in 8 groups of 4 pigs. A Vingmed System Five (General Electric Co. Cincinnati OH) was used at 1.5 MHz in B-mode to intermittently scan the kidney at 4 s intervals. A Sequoia 512 (Acuson, Mountain View CA) was used in the 1.5 MHz Cadence CPS mode with intermittent agent-clearance bursts at 4 s intervals. Kidneys were scanned transabdominally, or after laparotomy through a saline standoff. The Sequoia 512 probe was placed in contact with the kidney for one group. Definity (Lantheus Medical Imaging, N. Billerica, MA) was infused at 4 μl/kg/min (diluted 33:1 in saline) for 4 min during scanning. Results Blood-filled urinary tubules were evident on the kidney surface for all groups, except for the group with the probe in contact with the kidney. GCH was found by histology in 31.7 % ± 9.8 % of glomeruli in the center of the scan plane for 1.7 MPa transabdominal scanning and 1.5 % ± 2.9 % of glomeruli in sham samples (P<0.05). In addition, hematuria was detected after scanning, and tubular obstruction occurred in some nephrons. Conclusion Renal tissue damage was induced by CEDUS in the porcine model. This result, together with previous studies in rats, support an hypothesis that GCH would occur in humans from similar CEDUS.

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In Situ Kidney Insonation With Microbubble Contrast Agents Does Not Cause Renal Tissue Damage in a Porcine Model

Cited by 26 publications

References 16 publications

Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging

Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging

Bench-to-bedside review: Contrast enhanced ultrasonography - a promising technique to assess renal perfusion in the ICU

Contrast-Enhanced Diagnostic Ultrasound Causes Renal Tissue Damage in a Porcine Model

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