What are kidney stones?
A kidney stone is a type of rock that is composed of both minerals and salt and is often made up of calcium or uric acid. In the kidney, they cluster together, and they can spread to other parts of the urinary tract.
The size of the stones varies. Some are as tiny as the period at the end of this sentence — a fraction of an inch in length. Others can reach a few inches in diameter. Certain kidney stones can grow to be so large that they consume the entire kidney.
A kidney stone develops when an abnormally high concentration of certain minerals in your body accumulates in your urine. When you are dehydrated, your urine becomes more concentrated and contains a greater concentration of certain minerals. When mineral levels are elevated, the likelihood of developing a kidney stone increases.
In the United States, approximately 1 in every 11 people will develop a kidney stone.
Men, obese individuals, and those with diabetes are more likely to develop stones. Smaller kidney stones that remain in the kidney are frequently painless. You may be unaware that something is wrong until the stone enters your ureter — the tube through which urine travels from your kidney to your bladder.
Typically, kidney stones are excruciatingly painful. Without treatment, the majority of stones will pass on their own. However, you may require a procedure to break up or remove impassable stones.
Muscle relaxants given to the ureter can lessen the pain caused by passing a stone by relaxing the muscle around the ureter. The ER treats over half a million people per year for kidney stone issues. When passing through the urinary tract, the stones usually exit the body without much effort on the part of the person, but the process can be painful.
A treatment has now been devised by researchers at MIT and Massachusetts General Hospital that could make passing kidney stones less painful and/or less painful and quicker. They have found a new treatment for ureteric walls, a painful and dangerous condition that involves a twisted and narrowed ureter (the tube that connects the kidneys to the bladder).
To make passing stones move through the ureter more easily, the researchers propose loosening the ureter. According to Michael Cima, the David H. Koch Professor of Engineering in MIT’s Department of Materials Science and Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study, “We think this could have a significant impact on kidney stone disease, which affects millions of people.”
While it could also make it easier and less painful to insert stents into the ureter, which is done to prevent the tube from collapsing after a kidney stone is passed, this type of treatment may make it easier and quicker to perform the procedure for a nephrostomy tube. A recent Harvard-MIT Health Sciences and Technology PhD graduate, Christopher Lee, is the lead author of the study, which was published in the journal Nature Biomedical Engineering.
Local drug delivery
Kidney stones are made of crystals that form in the kidneys due to a high concentration of waste material in the urine without enough water to wash it away. Around 10 percent of the population will have a kidney stone in their lifetime.
After Brian Eisner and Cima began thinking about ways to improve the treatment of kidney stones, several years ago, they started investigating new ways to help the kidney stone population. In most cases, patients only have to wait for the stones to pass. This procedure usually takes 10 days.
Studies offer conflicting evidence as to whether the medication is effective in relieving pain, which causes the administration of painkillers to patients along with an oral medication meant to relax the ureter. Oral therapies that have been FDA-approved for kidney stones and ureteral dilation do not exist.
Cima and Eisner suggested administering a muscle relaxant directly to the ureter instead of via the bloodstream because of their belief that this route offered a better option. According to most studies, passing a kidney stone causes a lot of pain because of the muscle cramps and inflammation that occurs as the stone passes through the narrow ureter. Thus, loosening the muscles around the ureter could help with this process.
Lee first met with Cima about possible thesis topics when he enrolled in MIT’s Health Sciences and Technology programme, and his attention was then focused on research on kidney stones.
But kidney stones are typically treated in the same way today as they were around 1980, and there is a good deal of evidence to show that the medications used have no effect, according to Lee. It’s incredibly exciting to think of how many people this could potentially help. To learn which drugs worked well when given directly to the ureter, the researchers first set out.
They chose 18 pharmaceuticals used to treat high blood pressure and glaucoma, and exposed them to human ureteral cells, which were grown in a lab dish. To obtain a greater relaxation effect, it was thought that they could give these drugs directly to the ureter. This way, they could minimise any possible harm to the rest of the body.
Cima has discovered several drugs that have the intended effect, and in every case the required concentrations are higher than the recommended safe concentration when administered systemically.
Finally, the researchers performed extensive computational processing on nearly 1 billion cells in order to understand the concentration-dependent effects of a drug on the cellular response. Two medications proved to be especially effective, and further study revealed that when given together, they were even more effective.
One of these is a medication known as a ROCK inhibitor, which is used to treat glaucoma, and the other is a calcium channel blocker called nifedipine, which is used to treat high blood pressure.
They used a variety of different drug combinations to test their efficacy on ureters removed from pigs, and discovered that the frequency and length of ureter contractions could be reduced dramatically. The treatment nearly eliminated ureteral contractions in live pigs.
To test these medications, the researchers used a cystoscope, which is a small-gauge, hollow tube that is much like a catheter but has a small fibre optic channel. They discovered that these types of injections keep the drugs in the lining of the ureter, reducing the likelihood of any side effects.
To find out how long the muscle-relaxing effect lasts and how much relaxation is needed to increase the likelihood of passing a stone, the researchers state more research is needed.
After some time working on the project, they are starting their own startup company, Fluidity Medicine, to continue developing the technology.
While this method may help to relieve kidney stones, it might also be useful in reducing the tension in the ureter to aid in the insertion of a ureteral stent. When inserting an endoscope, it could help to have something on the other side.
The platform is set up to dispense medication into the ureter. First, we will focus on muscle relaxation. These treatments include ureteral stents, endoscopic surgery, and kidney stones. A number of other urological indications can all be hit, and each has a relevant patient population.
This research was supported by the MIT Institute of Medical Engineering and Science Broshy Fellowship, the MIT Deshpande Center for Technological Innovation, the Koch Institute Support (core) Grant from the National Cancer Institute, and the National Institutes of Health.