The U.Va. researchers have discovered that ultrasound – already in clinical use for imaging in hospitals around the country – appears to have therapeutic use to prevent the acute kidney injury that can result from heart surgery, abdominal surgery and other major procedures. While the discovery has been tested in mice so far, researchers are excited about the promise it could hold for humans.
If translated to human acute kidney injury, “a patient having cardiac surgery or other procedures where there’s high risk for acute kidney injury could potentially benefit from the application of a simple ultrasound procedure as a protective measure,” said U.Va.’s Dr. Mark D. Okusa, division chief of nephrology. “Non-invasive, no drugs, simple and portable – yet capable of protecting the kidneys from injury.”
Acute kidney injury may result from a loss of blood flow to the kidneys, causing a loss of kidney function and potentially prompting a cascade of serious, even life-threatening complications. “Patients who have acute kidney injury often develop lung injury, cardiac and liver dysfunction,” Okusa said. “Additional complications in the immune system and neurological systems occur as well. Those who are fortunate to survive often end up having progressive renal disease, or they end up on chronic dialysis.”
The U.Va. researchers, supported by the National Institutes of Health, were investigating the possibility of using microbubble-mediated, contrast-enhanced ultrasound to deliver drugs directly to the kidney when they discovered the protective benefit afforded by ultrasound alone. Joseph C. Gigliotti, a postdoctoral fellow in Okusa’s lab, first noticed the effect and pursued extensive studies characterizing and determining the mechanism of this effect in kidney protection.
Unexpectedly, Gigliotti found that the ultrasound treatment does not appear to act on the kidney, but on the spleen, an organ that helps regulate immune system responses.
“During acute kidney injury, the spleen sends out inflammatory signals that lead to further injury to the kidney,” Okusa said. “Exposing the spleen to ultrasound blocks these inflammatory signals and preserves kidney function. If you perform a splenectomy prior to ultrasound treatment, there’s no protection. So it’s the spleen that’s likely the target for this effect.”
The U.Va. researchers found that an ultrasound could be administered up to two days before an injury and still have a protective effect. After that, they found, the benefits began to wane. In the next stage of the research, Dr. Kambiz Kalantari, an associate professor in the Division of Nephrology, will lead human studies in preventing acute kidney injury through ultrasound treatment.
The findings have been published online by the Journal of the American Society of Nephrology. The article will also appear as a cover story in a forthcoming print edition. The credited authors are Gigliotti, Liping Huang, Hong Ye, Amandeep Bajwa, Kryt Chattrabhuti, Sangju Lee, Alexander L. Klibanov, Kalantari, Diane L. Rosin and Okusa.
An accompanying editorial salutes the U.Va. work and the promise it holds. “We believe that splenic ultrasound stimulation has a bright future ahead,” the authors wrote.
U.Va. has established itself as a world leader in pioneering important applications for focused ultrasound. In addition to the work under way in Okusa’s lab, other U.Va. researchers are exploring the potential of focused ultrasound for treating conditions such as essential tremor and Parkinson’s disease.