Every year, more than half a million Americans visit the emergency room for kidney stone problems. In most cases, the stones eventually pass out of the body on their own, but the process can be excruciatingly painful.
Researchers at MIT and Massachusetts General Hospital have now devised a potential treatment that could make passing kidney stones faster and less painful. They have identified a combination of two drugs that relax the walls of the ureter the tube that connects the kidneys to the bladder and can be delivered directly to the ureter with a catheter-like instrument.
Relaxing the ureter could help stones move through the tube more easily, the researchers say.
We think this could significantly impact kidney stone disease, which affects millions of people, says Michael Cima, the David H. Koch Professor of Engineering in MITs Department of Materials Science and Engineering, a member of MITs Koch Institute for Integrative Cancer Research, and the senior author of the study.
This kind of treatment could also make it easier and less painful to insert stents into the ureter, which is sometimes done after a kidney stone is passed, to prevent the tube from becoming blocked or collapsing.
Christopher Lee, a recent PhD recipient in the Harvard-MIT Division of Health Sciences and Technology, is the lead author of the study, which appears today in Nature Biomedical Engineering.
Local drug delivery
Kidney stones are made from hard crystals that accumulate in the kidneys when there is too much solid waste in the urine and not enough liquid to wash it out. It is estimated that about one in 10 people will have a kidney stone at some point in their lives.
Several years ago, Cima and Brian Eisner, who co-directs the Kidney Stone Program at MGH and is also an author of the paper, began thinking about ways to improve the treatment of kidney stones. While some larger stones require surgery, the usual treatment plan is simply to wait for the stones to pass, which takes an average of 10 days. Patients are given painkillers as well as an oral medication that is meant to help relax the ureter, but studies have offered conflicting evidence on whether this drug actually helps. (There are no FDA-approved oral therapies for kidney stones and ureteral dilation.)
Cima and Eisner thought that delivering a muscle relaxant directly to the ureter might offer a better alternative. Most of the pain from passing a kidney stone arises from cramps and inflammation in the ureter as the stones pass through the narrow tube, so relaxing the muscles surrounding the tube could help ease this passage.
Around this time, Lee, then a new student in MITs Health Sciences and Technology program, met with Cima to discuss possible thesis projects and became interested in pursuing a kidney stone treatment.
If you look at how kidney stones are treated today, it hasnt really changed since about 1980, and theres a pretty substantial amount of evidence that the drugs given dont work very well, Lee says. The volume of how many people this could potentially help is really exciting.
The researchers first set out to identify drugs that might work well when delivered directly to the ureter. They selected 18 drugs used to treat conditions such as high blood pressure or glaucoma and exposed them to human ureteral cells grown in a lab dish, where they could measure how much the drugs relaxed the smooth muscle cells. They hypothesized that if they delivered such drugs directly to the ureter, they could get a much bigger relaxation effect than by delivering such drugs orally, while minimizing possible harm to the rest of the body.
We found several drugs that had the effect that we expected, and in every case we found that the concentrations required to be effective were more than would be safe if given systemically, Cima says.
Next, the researchers used intensive computational processing to individually analyze the relaxation responses of nearly 1 billion cells after drug exposure. They identified two drugs that worked especially well, and found that they worked even better when given together. One of these is nifedipine, a calcium channel blocker used to treat high blood pressure, and the other is a type of drug known as a ROCK (rho kinase) inhibitor, which is used to treat glaucoma.
The researchers tested various doses of this combination of drugs in ureters removed from pigs, and showed that they could dramatically reduce the frequency and length of contractions of the ureter. Tests in live pigs also showed that the treatment nearly eliminated ureteral contractions.
For these experiments, the researchers delivered the drugs using a cystoscope, which is very similar to a catheter but has a small fiber optic channel that can connect to a camera or lens. They found that with this type of delivery, the drugs were not detectable in the animals bloodstream, suggesting that the drugs remained in the lining of the ureter and did not go elsewhere in the body, which would lessen the risk of potential side effects.
Ureteral relaxation
More studies are needed to determine how long the muscle relaxing effect lasts and how much relaxation would be needed to expedite stone passage, the researchers say. They are now launching a startup company, Fluidity Medicine, to continue developing the technology for possible testing in human patients.
In addition to treating kidney stones, this approach could also be useful for relaxing the ureter to help doctors insert a ureteral stent. It could also help when placing any other kind of instrument, such as an endoscope, in the ureter.
The platform pairs drug delivery to the ureter. We are eager to first target muscle relaxation, and as offshoots of that, we have kidney stones, ureteral stents, and endoscopic surgery, Lee says. We have a bunch of other urological indications that would go through different developmental pathways but can all be hit and all have meaningful patient populations.
The research was funded 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.
More:
New treatment could ease the passage of kidney stones - MIT News
- Christopher Lee Was Furious About This 'Lord of the Rings' Moment - Collider - April 2nd, 2024
- Airdate: The Life and Deaths of Christopher Lee - TV Tonight - April 2nd, 2024
- Christopher Lee's casual shorts and slippers outfit in Taiwan made heads turn - TODAY - March 16th, 2024
- Christopher Lee Dead: Horror Icon and Legendary Movie Villain Was 93 ... - February 19th, 2024
- "Chris wasn't hearing a bar of it": Christopher Lee Forcefully Auditioned For Another Lord of the Rings Character Before ... - FandomWire - February 11th, 2024
- 'Cancel everything': How Christopher Lee disciplines his son with this one phrase - Yahoo Singapore News - February 3rd, 2024
- Actress Fann Wong surprised by husband Christopher Lee on birthday - The Straits Times - February 3rd, 2024
- Fann Wong surprised by husband Christopher Lee on birthday - The New Paper - February 3rd, 2024
- Christopher Lee: The actor and hunter of Nazi war criminals - Far Out Magazine - January 9th, 2024
- Sir Christopher Lee's Favorite Performance is in a Film You've Never Heard Of - MovieWeb - December 12th, 2023
- Christopher Lee dies at the age of 93 - The Guardian - April 27th, 2023
- Christopher Lee - Tolkien Gateway - March 31st, 2023
- Christopher Lee filmography - Wikipedia - February 10th, 2023
- Where to Start with Christopher Lee - The Film Magazine - October 19th, 2022
- 'Were you desperate to get proposed to?' Christopher Lee crashes Rebecca Lim's new show and roasts her while dishing out relationship advice - AsiaOne - October 19th, 2022
- The Wicker Man TV Series In Development With Andy Serkis The Imaginarium And Studiocanal-Backed Urban Myth - Deadline - October 19th, 2022
- Tim Burton names his five favourite horror movies of all time - Far Out Magazine - October 19th, 2022
- Ten celebrities who served in the military, from Adam Driver to Prince Harry - The National - October 19th, 2022
- These 13 Actors Have Earned the Right to be Called Scream Kings - Dread Central - October 19th, 2022
- David W. Smith | Obituaries | thedailynewsonline.com - The Daily News Online - October 19th, 2022
- Jennifer Hudson Recounts "Fanning Out" Over Duet With Sheryl Lee Ralph: "I Wanted to Make Her Proud" - POPSUGAR - October 19th, 2022
- Tangipahoa Parish Jail - October 11th, 2022
- A monster calls: why the horror universe is an idea whose time has come - The Guardian - October 11th, 2022
- Oblong Box, The (Blu-ray Review) - The Digital Bits - October 11th, 2022
- Was that the balrog that killed Gandalf in the Rings of Power? - Polygon - October 11th, 2022
- Every James Bond movie ranked by critics, according to Rotten Tomatoes - Insider - October 11th, 2022
- Overwatch 2: All Voice Actors And Cast - eXputer - October 11th, 2022
- She got Covid-19 four times this year alone - The Star Online - October 11th, 2022
- Nursing School Collaborates with Nursing School in The Philippines - Boston College - October 2nd, 2022
- The Terrifying, Terrific Horror Movies of 1972 - Nerdist - October 2nd, 2022
- Lord of the Rings: The Return of the King: A beautiful conclusion to the iconic trilogy - The Shield - October 2nd, 2022
- Tyson Fury through the years: Photo gallery - MMA Junkie - October 2nd, 2022
- Duncan man jailed, accused of madness on meth - The Lawton Constitution - September 24th, 2022
- Conor McGregor "can't believe" he's being paid to film Hollywood movie - The Mirror - September 24th, 2022
- The Government of Malaysia Launches the National Energy Policy 2022 - 2040: What it Means for the Renewables Landscape - Lexology - September 24th, 2022
- New Brockton native Brandon Lee part of team cherishing NASCAR win at Bristol - Dothan Eagle - September 24th, 2022
- Cape Cod theater reviewers' thoughts on 2 scary plays and a comedy - Cape Cod Times - September 24th, 2022
- 'His presence is going to be there': Lee Roy Selmon will attend in spirit as trio of OU brothers honored with statue - The Oklahoma Daily - September 24th, 2022
- Nicolas Cage inspired by Christopher Lee for vampire movie Renfield - The Digital Fix - September 16th, 2022
- Reece Shearsmith Tells Richard Herring About Christopher Lee - Beyond The Joke - September 16th, 2022
- 8 Horror Movies So Awful They Were Pulled From The Cinema - WhatCulture - September 16th, 2022
- Man-Thing Makes his MCU Debut in Werewolf by Night - Here's what we know about Man-Thing - Attack of the Fanboy - September 16th, 2022
- Summer of Blood (Blu-ray Review) - The Digital Bits - September 16th, 2022
- Get it over with: Suspect in Kokomo child exploitation case tells police to arrest him on the spot - FOX 59 Indianapolis - September 16th, 2022
- Alabama says it won't be ready to use nitrogen hypoxia method at Sept. 22 execution - USA TODAY - September 16th, 2022
- Christopher Lee, The Real-Life "Most Interesting Man In The World" - August 31st, 2022
- Inside The Fact And Fiction Of Christopher Lee's World War II Service - August 31st, 2022
- How to watch The Lord of the Rings movies and the series in chronological order - Lifestyle Asia India - August 31st, 2022
- Court and arrest reports for Martinsville and Henry County - Martinsville Bulletin - August 31st, 2022
- Every Tim Burton Movie Ranked from Worst to Best - Consequence - August 31st, 2022
- Court lists defendants to appear in Criminal Division on Thursday - Magnoliareporter - August 31st, 2022
- Lee County School Board makes minor revision to Parents' Bill of Rights - Wink News - August 31st, 2022
- A Cardiologist Breaks Down the AHA's New Report on the Most Common Heart Disease Symptoms Best Life - Best Life - August 31st, 2022
- Exclusive Interview: Director Philippe Mora On His Films With Christopher Lee - FANGORIA - August 14th, 2022
- 10 films turning 10 in 2022 - NewsNation Now - August 14th, 2022
- Persephone and the Poultry of the Night | Thumper Forge - Patheos - August 14th, 2022
- Unexpected Demands Made By Lord Of The Rings Actors - Looper - August 14th, 2022
- Rings of Power: Everything you need to know about Amazon's 1bn Lord of the Rings prequel - The Mirror - August 14th, 2022
- Slash Tells Us Why There Will Never Be a Guns N Roses Movie - MovieMaker Magazine - August 6th, 2022
- On the record for Aug. 4 - Seymour Tribune - August 6th, 2022
- Judge Talley will hear criminal docket on Thursday - Magnoliareporter - August 6th, 2022
- Dr. Christopher Reber Receives ACCT 2022 Northeast Regional Chief Executive Officer Award - The Hudson Reporter - August 6th, 2022
- Theatre Review: This 101 Dalmatians is barking up the wrong tree - The New European - August 6th, 2022
- Christopher Lee Euro Films, Dennis Hopper's 'Out of the Blue' Among Titles Due on Disc From Severin and MVD July 26 Media Play News - Media Play News - July 28th, 2022
- 25 Scariest Movies of All Time (2022 Edition) - Cultured Vultures - July 28th, 2022
- Fans Wonder Why a Fantasy Epic Too Big to Fail Did Just That - We Got This Covered - July 28th, 2022
- The Best Witch Movies of all Time, Ranked - The Mary Sue - July 28th, 2022
- NASCAR Driver Christopher Bell and CRAFTSMAN Raise Awareness for Children's Miracle Network Hospitals; No. 20 Special Edition Paint Scheme to be... - July 28th, 2022
- Singer Stefanie Sun turns 44 with cakes and loved ones - The Straits Times - July 28th, 2022
- Tony Dow dead: Wally Cleaver 'Leave It to Beaver' actor was 77 - USA TODAY - July 28th, 2022
- Roane Co. authorities looking for man convicted of neglecting and murdering an elderly relative - WBIR.com - July 20th, 2022
- 22 Incredible Facts About The Life and Career Of Sir Christopher Lee - July 20th, 2022
- Police and Fire Report - Winchester Sun - Winchester Sun - July 20th, 2022
- What We Do in the Shadows cast shares their favorite vampire movies, books, and more - Polygon - July 20th, 2022
- Courteney Cox Set To Make Horror Movie History With 'Scream 6' - We Got This Covered - July 20th, 2022
- Every James Bond Movie, Ranked: The Best of Bond - CNET - July 20th, 2022
- Grandparents of Dean Kerrie say he was just defending his mother and should not be jailed - Sunday World - July 20th, 2022
- Ray Wise Has Always Been More Than "That Guy" - Defector - July 20th, 2022
- Angela Ledgerwood on the Psychic Relief of Reading - Literary Hub - July 20th, 2022
- Athens man charged with manslaughter in fatal hit and run - News Courier - July 12th, 2022
Reviewed and Recommended by Erik Baquero