From PKD Foundation, by Dr. David Baron, Chief Scientific Officer
There are some truly fascinating techniques in the research field being used to help increase our understanding of PKD. This week, our Chief Scientific Officer, Dr. David Baron, shares how the development of kidney organoids may help us get closer to new treatments:
Cell biologists began to grow cells derived from various tissues and organs into what are known as cell cultures in glass dishes (in vitro). These cells could accomplish some of the functions they were designed to do, such as secrete proteins or direct the movement of salts, water, and other across them. However, these cell cultures were mostly two-dimensional and didn’t look anything like the organs or tissues they came from. Another problem, aside from lack of structure, is that these cells would divide only so many times, and with increasing cell division, the cells would often lose their original functions that distinguished them in the first place.
What these biologists really wanted to build was a cell culture system by which the freshly isolated cells could grow into three dimensional structures rather than flat sheets, or even better, grow into structures that, to some extent, reflected where they came from. An early example of this is the use of Madin-Darby Canine Kidney cells or MDCK cells, first established to study viral infections. Scientists later discovered that they could grow these cells into three dimensional tubules that could transport salts and water, functions similar to what the mammalian kidney tubules do. However, these were simple structures of the same cell type that had only a vague resemblance to the complicated kidney from which they were derived.
Dogs are not humans, however. Recent exciting research, in part funded by the PKD Foundation, has shown that human pluripotent stem cells (hPSCs) derived from human skin biopsies can be grown into kidney organoids. Pluripotent stem cells can be induced to change (differentiate) into many distinct cell types. For example, more than 20 distinct cell types required to accomplish the many functions of the human kidney. Much more complex than MDCK cells in culture, these hPSCs can be grown into organoids that resemble in some key ways the structure of the human kidney. The latest research is seeking to grow blood vessels and connective tissue to augment the organoids. Someday this research could be used to actually grow a functional kidney! More importantly for PKD research right now, these organoids can be made to express the ADPKD mutation that causes the disease.
Dogs are not humans, however. Recent exciting research, in part funded by the PKD Foundation, has shown that human pluripotent stem cells (hPSCs) derived from human skin biopsies can be grown into kidney organoids. Pluripotent stem cells can be induced to change (differentiate) into many distinct cell types. For example, more than 20 distinct cell types required to accomplish the many functions of the human kidney. Much more complex than MDCK cells in culture, these hPSCs can be grown into organoids that resemble in some key ways the structure of the human kidney. The latest research is seeking to grow blood vessels and connective tissue to augment the organoids. Someday this research could be used to actually grow a functional kidney! More importantly for PKD research right now, these organoids can be made to express the ADPKD mutation that causes the disease.
One of the barriers to finding effective treatments for PKD is the lack of an in vitro system to screen potentially promising molecules that could become novel drugs. Such an in vitro system allows for high throughput screening, which is orders of magnitude more efficient than relying on rodent models of PKD. Kidney organoids, particularly those containing the ADPKD mutation, while not quite high throughput, are much more efficient than animal models for screening molecules that could be the next generation of drugs for the treatment of PKD. The PKD Foundation is proud to play a continuing role in this exciting research!
Gift of Life
Three times a week, 52 weeks a year, Steve Dunn makes the trek from his Orléans home and settles into a comfy chair in the basement of the Riverside Hospital. He’ll be there for the next 4 1/2 hours as his blood pumps through a life-saving kidney dialysis machine.
It’s a routine he’s been doing for five years.
“It’s like a part-time job, really,” said Dunn, 47.
Frustrated by his half-decade wait for a kidney donor, Dunn has turned the back of his GMC pickup into a moving billboard for organ donors.
“Asking for help. I need a kidney transplant,” reads the print on the truck tailgate. “Many others like myself need your help. Don’t take your organs to Heaven. Save a life instead.”
Dunn added the slogan to his truck about a month ago, not just to help his own predicament, but for others who are languishing on transplant lists.
“It’s probably not going to help me — although it would be a miracle if it did — but maybe it will help people down the road,” he said. “At least it might make people think about organ donation.”
Dunn is one of 4,300 Canadians waiting for kidney transplant. Kidney transplants are one of the oldest and most common organ transplants. The first successful transplant took place in Illinois in 1950 from a cadaver. Two years later a kidney was successfully transplanted from a living donor.
Today, the operation boasts a success rate of up to 95 per cent, according to the Kidney Foundation of Canada. But there are still not enough organs available.
Dunn suffers from high blood pressure which led to a stroke 10 years ago and eventually to kidney failure. His kidneys now operate at under 10 per cent efficiency, meaning dangerous toxins build up in his blood stream that must be removed through dialysis.
His blood type is O-positive, meaning he can donate blood to anyone, but can only accept blood or an organ from someone else with the same blood type. His sister has diabetes and is ineligible to donate. His mother is too old. His brother is the wrong blood type.
The weekly need for dialysis means the former delivery driver can’t hold a full-time job.
That’s one of the hidden costs that affects so many people with kidney disease, said Elizabeth Myles, executive director of the Kidney Foundation of Canada. Even the cost of travel and parking three times a week at hospital can be prohibitive. People with kidney disease face higher food bills because of the cost of a healthy, kidney-friendly diet that avoids cheaper, processed foods.
“The financial burden of kidney disease is one of the things we want to raise awareness about,” Myles said. “There are a lot of costs passed on to people with kidney disease.”
About four million Canadians, or one in 10, suffer from chronic kidney disease and that number has been increasing, particularly among the young, she said.
For many, like Dunn, a transplant is the best hope for a normal life.
“Even though the vast majority of Canadians support organ donations according to polls, the number who actually consent is relatively small,” Myles said. It’s important that those who do wish to donate organs, register as a donor and let their loved ones know of their wishes.
Dunn is still waiting to hear if a donor is available, but his truck has been turning heads. Once, he came out of a bank at Place d’Orléans and found a man waiting to speak to him.
“He said, ‘I want to give you a kidney’,” Dunn recalled. “He was in a wheelchair but he said that he wanted to help.”
Dunn helped the man pass his name along and though he doubts the man will be a suitable donor, he was touched by the stranger’s selflessness.
“It was unbelievable. You don’t see that very often in the world today.”
In Ontario, organ donation is no longer linked to your driver’s licence. Instead, registration is done through Service Ontario or online at beadonor.ca.
March is Kidney Month in Canada. For more information, visit the Kidney Foundation of Canada at kidney.ca
Living with PKD
From Chicago Tribune, by Robert McCoppin
Medical marijuana in Illinois would become legal permanently under a proposed new state law, and the list of qualifying conditions would expand greatly to include common conditions such as osteoarthritis, autism and chronic pain.
The former top regulator of medical marijuana in the state, Bob Morgan, is a new Democratic state representative from Deerfield and the chief sponsor of the plan. He says he knows of no significant opposition, and expects lawmakers to approve the measure this spring.
The former top regulator of medical marijuana in the state, Bob Morgan, is a new Democratic state representative from Deerfield and the chief sponsor of the plan. He says he knows of no significant opposition, and expects lawmakers to approve the measure this spring.
“We’ve had a (pilot program) that shows this is a safe program without diversion (to illegal use),” Morgan said. “It’s helping people who are struggling with serious medical conditions.”
The medical marijuana program allows patients with any of about 40 serious medical conditions, such as cancer and AIDS, to qualify for 2.5 ounces of marijuana every two weeks with their doctors’ approval.
The pilot program has evolved a couple of times since Illinois lawmakers approved it with bipartisan support in 2013, and sales began in late 2015. Former Republican Gov. Bruce Rauner later approved extending the life of the program to mid-2020 and added post-traumatic stress disorder and terminal illness as qualifying conditions, but abolished the medical cannabis advisory board that had recommended adding more conditions.
Last year, Rauner signed a law to allow medical marijuana as an alternative to prescription opioids, and ended a requirement for patient fingerprints and criminal background checks. Those two measures significantly expanded the program to its current size of about 58,000 patients, but so far the program remains smaller than in many other states, mainly because it doesn’t allow patients to use the drug for pain, the most common qualifying condition elsewhere.
The General Assembly is also expected soon to consider legalizing recreational use of cannabis, but if approved it would likely take until next year before sales are allowed. One advantage of medical marijuana would be to avoid taxes placed on recreational marijuana.
By many accounts, the program has worked as intended. Many of the patients say they use marijuana to help them get off other stronger prescription drugs. Police have not reported any major problems with people selling or using medical marijuana without certification.
Even Healthy and Productive Illinois, a nonprofit group which is fighting the proposed legalization of recreational marijuana, does not oppose medical marijuana or decriminalization, lobbyist Tim McAnarney said. He wasn’t able to comment on the proposal to make the medical program permanent, saying he’d have to see how much it would expand use.
The bill would also allow doctors to be paid by medical marijuana businesses or patients. Morgan said that doctors would still be prohibited from getting kickbacks for referrals, but this would allow them to be paid for research.
As proposed, new qualifying conditions would be chronic pain, autism, irritable bowel syndrome, migraines, osteoarthritis, anorexia nervosa, Ehlers-Danlos syndrome, Neuro-Behcet's autoimmune disease, neuropathy, polycystic kidney disease and superior canal dehiscence syndrome.
Research on the effects of cannabis on autism is very limited. Many doctors and several medical groups warn against using a drug which has not been thoroughly tested and approved by the U.S. Food and Drug Administration, and that the federal government classifies as being addictive with no medicinal value.
The American Academy of Pediatrics opposes the use of medical marijuana, noting that it can harm memory, learning and coordination, and lead to psychological problems or drug dependence. But the AAP supports “compassionate use” for children with debilitating or life-limiting diseases, and urges the government to relax the classification of the drug to allow more research.
Mothers Advocating Medical Marijuana for Autism, a nonprofit advocacy group, lists several studies suggesting preliminary support for the treatment, and counting nine states that allow the drug for autism.
Marijuana has been shown to be helpful for many of the conditions that accompany autism, such as epilepsy, pain, aggression and anxiety, said Wendy Fournier, president of the National Association of Autism. She said cannabidiol oil tinctures have helped reduce her autistic daughter’s seizures and helped her sleep.
Recreational marijuana has been legal in Colorado for years. What can Illinois learn before its residents start firing up? »
“There aren’t any good alternatives, so if this is working for some people, go for it, let’s do it,” she said. “This is a potentially life-changing treatment for some people.”
The proposed bill also includes language to allow unspecified “medical conditions or symptoms for which a person may benefit from the use of medical cannabis,” but Morgan said he would remove that language as a compromise to gain broader support.
Those conditions were previously recommended by the former advisory board, and some were the subject of lawsuits and court orders, but the Rauner administration refused to approve them.
Jim Champion, a veteran with multiple sclerosis, was looking forward to changes the bill would bring, such as no longer forcing patients with chronic conditions to recertify their ailments. With his wife Sandy, the Champions lobbied to pass the original law, and worked with Morgan on the new bill.
One important change, they said, was to have the state Department of Public Health make provisions for veterans to qualify under for medical marijuana as an alternative to opioids. Because the drug remains prohibited under federal law, Veterans Affairs doctors are prohibited from certifying their patients.
“We fully support this and look forward to making it permanent,” Sandy Champion said.
The bill would also allow patients to have multiple caregivers who could buy their medical marijuana for them, would allow transportation of the drug after it is opened, and would provide for returns of damaged or inadequate products.
rmccoppin@chicagotribune.com
Kidney Care System
March is National Kidney Month, a perfect time to reflect on the progress made in kidney care and efforts to advance that success to the next level. The challenge facing individuals with kidney diseases requires a united effort from Congress, the Administration, the National Institutes of Health (NIH) and the kidney care community. Fortunately, the collective commitment and momentum are in place, and now is the time to seize on this opportunity to maintain this forward trajectory.
More than a decade ago, the kidney care community set an ambitious goal to improve patient care outcomes and reduce health care costs. We have made significant strides in advancing kidney health with numerous multi-disciplinary work groups consisting of clinicians, providers, patient groups, researchers and manufacturers working together to: develop performance measures for accountability and endorsement through the National Quality Forum process; undertake a successful initiative to improve survival in the first year of dialysis; establish a strategic “quality blueprint” that identifies the leverage points for quality improvement; and publish a framework for considering patient reported outcomes (PROs) in this vulnerable population. All of these initiatives challenged us as a community while we worked constructively with policymakers on meaningful programs and policies that advance us toward the common goal of higher quality care and quality of life for patients with kidney diseases.
Now, a new analysis by Discern Health, which examined data from the government’s United States Renal Data System (USRDS), confirms that patient outcomes have significantly improved during the past decade. All-cause dialysis mortality rates have fallen, as have hospital admission rates for individuals who rely on dialysis care for long-term care needs or while they await a kidney transplant. In fact, gains in survival rates among this population now outpace those for cancer, heart disease, diabetes, and many other serious chronic diseases. Incredibly, the gains in kidney care come even as some chronic diseases saw worsening mortality – heart failure and myocardial infarction among them.
Despite the fact that individuals with kidney failure are among the most complex and costly Medicare beneficiaries to treat, improvements in dialysis care have led to substantial cost savings for Medicare. Discern Health confirmed that Medicare’s spending growth on individuals in kidney failure slowed from 7 percent to 1.5 percent over a 10-year period.These savings persist even after accounting for the fact that the number of Americans who require dialysis has risen sharply in the last few decades, and are now in the billions of dollars.
The kidney care community’s and policymakers’ efforts to advance access, choice, and quality while maintaining the integrity of the Medicare ESRD benefit have had positive, measurable results, yet there is still much more room to improve. We can—and must—do better to build on the real gains we’ve made, and focus on other critical areas such as prevention, access and choice, and increased investment in research and innovations.
In order to challenge ourselves again, we need a bigger and bolder agenda aimed at further boosting survival rates, focusing on patient-centered care and quality of life, improving access to treatment, investing in innovative therapies and medicines, and ensuring kidney health is more effectively addressed before individuals reach kidney failure.
This ambitious agenda requires working collaboratively with policymakers and other stakeholders through public-private partnerships to achieve even greater gains for kidney health. Any constructive collaboration must address not only quality and innovation but also the chronic Medicare underfunding as reported by the independent, nonpartisan Medicare Payment Advisory Commission (MedPAC) in January. This is particularly concerning in the ESRD program as approximately 85 percent of patients rely on government funding for their care.
Last year, the kidney community held a briefing on Capitol Hill with leaders from the kidney care stakeholders, bipartisan members of Congress, and senior representatives from NIH and CMS to share a bold vision for kidney care in America and commit to improving the lives of the tens of millions of Americans living with kidney diseases.
As strong supporters of value in the U.S. health care system, we commend Department of Health and Human Services Secretary Alex Azar’s efforts to foster even greater improvements for the 30 million Americans living with ESRD. Our shared commitment to programs like the Kidney Innovation Accelerator (Kidney X), which is running a competition to develop the new generation of advanced kidney care technology, underscores our commitment to continuously improving kidney health. In addition, we strongly support the interests of HHS and the Center for Medicare & Medicaid Innovation in advancing the care for individuals with chronic kidney diseases before kidney failure occurs, and for significantly increasing the number of patients receiving dialysis at home or a kidney transplant.
The administration has already shown a welcome focus and dedication to prioritize policies and programs to address disease affecting millions of Americans. Secretary Azar vowed in remarks to the National Kidney Foundation that “together, we can deliver much better care, and longer lives, for Americans with kidney disease.” In Congress, a bipartisan group of lawmakers in the House and Senate are working on an updated version of the 2018 Chronic Kidney Disease Improvement in Research & Treatment Act that will be introduced later this year.
As someone who has been a practicing nephrologist for more than 40 years, it is exciting to see the community standing shoulder-to-shoulder with the policy community. We are excited to do our part to advance this bold agenda with a renewed and reimagined commitment to innovation.
To that end, we look forward to continued collaboration with policymakers in Congress and the administration to further help patients with chronic kidney diseases, kidney failure and transplants live longer, healthier, and more fulfilling lives.
Nissenson is chair of Kidney Care Partners.
