New Discoveries

NEW DISCOVERIES: Ultrasound may prevent injuries to kidney during surgery

Joseph Gigliotti, a postdoctoral fellow in Nephrology division chief Mark Okusa’s lab, recently discovered that ultrasound appears to have a therapeutic use in preventing acute kidney injury, which can sometimes result from heart surgery, abdominal surgery, or other major procedures. He has tested the discovery in mice, and he and Okusa are excited about the promise it could hold for humans.

“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 Okusa. “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. Additional complications in the immune system and neurological systems can occur as well,” Okusa said. “Those who survive often end up with progressive renal disease, or on dialysis.”

Okusa’s lab, supported by an NIH grant, was investigating the use of microbubble-mediated, contrast-enhanced ultrasound to deliver drugs directly to the kidney, when they discovered the protective benefit from ultrasound alone. Gigliotti then pursued extensive studies characterizing and determining the mechanism of this effect in kidney protection.

Unexpectedly, he found that ultrasound treatment does not appear to act on the kidney but rather 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 explained. “Exposing the spleen to ultrasound blocks these inflammatory signals and preserves kidney function. If you perform splenectomy prior to ultrasound treatment, there’s no protection. So it’s the spleen that’s likely the target for this effect.”

They found that an ultrasound could be administered up to two days before an injury and still have a protective effect; after that, the benefits begin to wane. In the next stage of research, UVA Nephrology colleague Kambiz Kalantari will lead human studies of ultrasound treatment to prevent acute kidney injury.

The findings have been published online by the Journal of the American Society of Nephrology, and will appear as a cover story in a forthcoming print edition. Study co-authors were Gigliotti, Liping Huang, Hong Ye, Amandeep Bajwa, Kryt Chattrabhuti, Sangju Lee, Alexander Klibanov, Kalantari, Diane Rosin, and Okusa. An accompanying editorial salutes their work and the promise it holds. “We believe that splenic ultrasound stimulation has a bright future ahead,” the editors wrote.