More than 2 million patients come to emergency rooms in the US each year with symptoms related to kidney stones including intense pain, dizziness, nausea, infections, and sepsis. The occurrence of stones is increasing rapidly as a result of the aging of the US population, and the increases in obesity and diabetes in the population.
Emergency room visits for stones are expensive because of the need for urinalysis, bloodwork and imaging for diagnosis and determination of treatment. A blocked ureter can lead to Sepsis in these patients, so diagnosis is urgent.
Treatment is guided by the size and location of the stone – For stones 8mm and smaller positioned in the ureter (more than 1 million patients each year) , most of these patients are given prescription narcotics and sent home to wait for the stones to pass naturally. The average time to passage can exceed a month, and there are many negative consequences associated with missed work, lost opportunities, and the health impact of the stone passage. As many as 1 in 3 patients who use narcotics for a full month can become addicted.
Applaud Medical’s Acoustic Enhancer
Applaud Medical has developed a breakthrough medical device technology for treatment of kidney stones – Applaud Acoustic Enhancer. The Acoustic Enhancer is a micro bubble consisting of a gas core with a lipid shell. The lipid shell is very similar in structure and composition to the cellular membrane in human cells, and has been accepted by the FDA as a low-risk biocompatible device for use in the urinary system within Applaud’s current clinical trial.
When small amounts of Acoustic Enhancer formulation are placed into the urinary system, the millions of microbubbles in each milliliter infusion drift throughout the urine, and some will accumulate near the surface of the stone.
Acoustic Enhancer with URS-LL
When subjected to acoustic impulses from Ureteroscopy Laser Lithotripsy (URS-LL) or other therapies, the Acoustic Enhancer is designed to produce rapid, large‐amplitude expansions and contractions, then a final collapse. This collapse near a hard surface triggers inertial cavitation, which causes erosion and fragmentation of the stone. The video on the right is recorded from a URS-LL procedure with Applaud’s Acoustic Enhancer in a human subject.
The optical fiber is seen directing the laser light at the kidney stone. The Acoustic Enhancer is visible as a milky cloud in the first few seconds of the video. At the 6th second, the laser begins to activate the fragmentation process, causing the formation and collapse of vapor bubbles to fragment the stone at the tip of the optical fiber. In parallel, our Acoustic Enhancer is capturing energy from the laser and causing cavitation and fragmentation on all other surfaces of the stone, and on fragments as they move away from the optical fiber. The result is faster fragmentation, fewer and smaller fragments and better outcomes.
The high-speed microscope video on the left shows one side of an artificial kidney stone with Applaud Acoustic Enhancer microbubbles all over the surface. An optical fiber from a pulsed laser is pointed at the opposite side, as would be the case during a normal URS-LL procedure. When the laser pulse forms a vapor bubble that expands and collapses on the opposite side, our Acoustic Enhancer microparticles positioned all over all surfaces of the stone also expand and collapse, causing cavitation and erosion.
In this case, we see that laser pulses targeting one side of a kidney stone can excite our Acoustic Enhancer microparticles on the opposite side of the stone and can cause cavitation and erosion.
Acoustic Enhancer with External Ultrasound
Applaud’s Acoustic Enhancer can also be used with externally-applied, low-intensity, unfocused ultrasound to capture acoustic energy. When exposed to this external ultrasound, the Acoustic Enhancer expands, collapses and causes cavitation which fragments the stone.
Applaud uses our Acoustic Enhancer with our proprietary low-intensity unfocused ultrasound for treatment of smaller stones that have entered and become stuck in the ureter. This treatment method is designed to be carried out in the urologist’s office without anesthesia or imaging, and can provide relief to many patients who are normally sent home with narcotics and asked to wait days or weeks for the stone to pass naturally.