Background: Inflammation mediates the tissue injury that occurs during acute kidney injury (AKI). We have shown prior ultrasound (US) exposure reduces AKI and inflammation in mice. How US modulates inflammation is unknown. Therefore, the objective of the current study was to determine if prior US exposure modulates the initial inflammatory response to AKI.

Methods: Male C57BL/6 mice were anesthetized and exposed to US (7MHz, MI = 1.2) using Siemens Acuson Sequoia 512 system with a 15L8w transducer. 24h after US exposure, mice were subjected to bilateral renal ischemia-reperfusion injury (IRI). For survival studies, mice were maintained for 7d after IRI. For acute studies, mice were euthanized and tissue samples were collected after 0h (no reperfusion) and 0.5h after IRI. AKI was assessed by measuring plasma creatinine. Neutrophils were quantifi ed by FACS and renal IL1ß mRNA expression was determined by RT-PCR.

Results: Exposure to US 24h prior to IRI signifi cantly improved 7d survival as compared to IRI alone (mortality of 25% vs 87%, P=0.004). The protective effect of US was observed 0.5h after reperfusion, where mice pretreated with US had a 67% reduction (P=0.02) in plasma creatinine compared to mice receiving IRI alone. IRI resulted in a 3-fold increase in renal neutrophils, a phenomenon prevented with prior US exposure (P=0.05). However, prior US did not infl uence (P=0.99) circulating neutrophils 0.5h after reperfusion, suggesting that US modulates traffi cking of neutrophils into the kidney. US reduced (P=0.05) kidney IL1ß mRNA expression by 50% after ischemia alone (no reperfusion), suggesting prior US exposure modulates the response of the kidney to ischemic damage.

Conclusions: The results demonstrate that prior US exposure decreases the mortality associated with IRI in mice. This could be due to an US-induced reduction in ischemic tissue damage, which in turn reduced neutrophil accumulation following reperfusion. Identifying the mechanism responsible will shed light on new therapeutic targets for AKI.