ROCHESTER, Minn. — While immunosuppressive medications are critical to prevent rejection of transplant organs, they also come with plenty of downsides. They can cause harsh side effects, like headaches and tremors, and increase the risk for infection and cancer. But what if there was a way to prevent organ rejection without using these medications?

That goal fuels the work of Mark Stegall, M.D., a longtime Mayo Clinic transplant researcher. He leads a team of researchers developing pioneering therapies to prevent organ rejection without the need for immunosuppression. A recently published study in the American Journal of Transplantation is offering hope for patients.

Using stem cells to prevent organ rejection

Mayo Clinic participated in the multisite phase 3 clinical trial detailed in the study. The goal was to see whether people who simultaneously received both a kidney and stem cell transplant from a closely matched sibling could discontinue all immunosuppressive medications after a year. The results were promising. The study found that 75% of participants were able to stop taking the medication for more than two years. At Mayo Clinic, three patients participated, with two off immunosuppression medications for over three years and one on a low dose.

"I've been involved in transplant research for more than 30 years, and we've done quite a few amazing things. But in the scheme of things, this research is right at the very top. It's been a goal — to be able to safely get transplant recipients off immunosuppression — for longer than I've been doing this. We're very excited about it," says Dr. Stegall, a co-author of the study.

The research being done across Mayo Clinic is part of a growing trend in transplant to explore ways to use cellular therapies to prevent organ rejection. It is also a cornerstone of Mayo Clinic's Transforming Transplant Initiative, which has the bold goal of ensuring everyone who wants a transplant can get one and to make transplants more successful.

To qualify for the clinical trial, the transplant recipients and donors needed to be siblings whose tissue types closely matched. The donor agreed to donate their stem cells in addition to their kidney to their sibling. The recipient receives the transplant, undergoes radiation and then receives the stem cell transplant. The goal was to wean recipients off immunosuppression medication after a year.

'Almost like the transplant didn't happen'

For Minnesota native Mark Welter, the results have been better than he imagined. Four years ago, he needed a kidney transplant due to polycystic kidney disease, an inherited condition that causes cysts to grow on the kidneys. The Mayo Clinic patient volunteered to be a part of the clinical trial in hopes of not having to worry about immunosuppression medication the rest of his life. His younger sister Cindy Kendall immediately stepped forward to donate a kidney and her stem cells to help her brother.

"Being able to see him get off those medications has been amazing," Cindy says. "He just gets to live his life to the fullest. He has been able to see both of his daughters get married and meet his grandchildren."

Watch: Inteview with Mark Welter, Cindy Kendall and Dr. Mark Stegall

Mark has not taken immunosuppression medication for more than three years.

"I feel fantastic. I actually feel like I did before the transplant, which has been the greatest thing," Mark says. "It's almost like the transplant didn't happen."

There is still plenty of work to be done to advance this research. This clinical trial only involved siblings with closely matching tissue types. Researchers want to know if stem cell transplants can prevent rejection in recipients paired with a less closely matched donor.

"Even in closely matched siblings, immunosuppression is needed lifelong. We have seen stopping medications even at eight to 10 years post-transplant leads to rejection. Our goal is to find ways to reduce or stop immunosuppressive medications after transplant so patients can have longer lasting kidneys with fewer side effects," says Andrew Bentall, M.B., Ch.B., M.D., a Mayo Clinic transplant nephrologist.

Journalists: Press kit, including b-roll, photos and interviews are available here. Clinical trial participants and Mayo researchers are available for interviews. Please contact newsbureau@mayo.edu to schedule.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

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• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — Cancer, infections and heart disease pose the greatest risk to kidney transplant recipients ― not organ rejection ― according to a recently published Mayo Clinic study. Researchers discovered that recipient death due to factors other than organ rejection is the leading cause for transplanted kidney loss. Only 1 in 4 transplanted kidney losses were caused by organ rejection.

"Immunosuppression medication to prevent rejection is often the focus when caring for patients posttransplant. But this study highlights the increased risk of death from cancer and infection for transplant patients, especially those who are older and have diabetes," says Andrew Bentall, M.B., Ch.B., M.D., a Mayo Clinic nephrologist and the study's co-first author. The study was recently published in Transplantation Direct.

The study, the largest to examine reasons for transplanted kidney loss, involved 5,752 patients who underwent a kidney transplant at Mayo Clinic kidney transplant programs in Arizona, Florida or Minnesota between 2006 and 2018. Of those patients, 691 patients died with a functioning kidney. Researchers found that 20% of these patients died from cancer; 19.7%, infection; and 12.6%, cardiac disease.

Another 553 patients lost their transplant due to the failure of a transplanted kidney. Of these patients, 38.7% of the patients' kidneys failed due to rejection; 18.6%, glomerular diseases; and 13.9%, tubular injury.

Researchers uncovered two types of kidney transplant recipients who are at high risk after transplant. The first are younger, nondiabetic patients who develop kidney failure due to organ rejection. The second group includes older, often diabetic patients who are at risk of death due to causes not associated with organ rejection, including cancer, infections and heart disease.

Dr. Bentall says this study makes clear that care providers need to treat these two populations differently to minimize risks. For younger patients, that includes focusing on immunosuppression medication to prevent rejection. For older, often diabetic patients, it is critical to address chronic health issues, such as obesity, high blood pressure and diabetes. Focusing on these lifestyle changes is critical for improving long-term outcomes for kidney transplant recipients.

"It is important for these older patients that care providers emphasize the need for ongoing lifestyle changes that address obesity, high blood pressure and diabetes. Those include losing weight, exercising and new strategies for managing diabetes," he says. "Making those changes could potentially impact the patient's life and kidney outcomes more than immunosuppression therapies."

Other authors are Massini Merzkani, M.D.; Byron Smith, Ph.D.; Xiomara Benavides Lopez, M.D.; Matthew D’Costa, M.D.; Walter Park; Walter Kremers, Ph.D.; Naim Issa, M.D.; Andrew Rule, M.D.; Harini Chakkera, M.D.; Kunam Reddy, M.B.B.S.; Hasan Khamash, M.D.; Hani Wadei, M.D.; Martin Mai, M.D.; Mariam Alexander, M.D.; Hatem Amer, M.D.; Aleksandra Kukla, M.D.; Mireille El Ters, M.D.; Carrie Schinstock, M.D.; Manish Gandhi, M.D.; Raymond Heilman, M.D.; and Mark Stegall, M.D. — all of Mayo Clinic.

This research was supported by the National Institutes of Health.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. For information on COVID-19, including Mayo Clinic's Coronavirus Map tracking tool, which has 14-day forecasting on COVID-19 trends, visit the Mayo Clinic COVID-19 Resource Center.

Media contact:

• Heather Carlson Kehren, Mayo Clinic Public Affairs, newsbureau@mayo.edu

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ROCHESTER, Minn. — An estimated 1 in 10 people worldwide have chronic kidney disease, but most of them don't know it. That lack of awareness is especially concerning because people with chronic kidney disease who are infected with COVID-19 are at higher risk for serious illness.

It is important that people understand their risk for developing chronic kidney disease and take steps to prevent it, says Andrew Bentall, M.B., Ch.B., M.D., a Mayo Clinic nephrologist.

"Managing risk factors such as high blood pressure, diabetes and obesity will reduce the chances of developing kidney disease," Dr. Bentall says. "Once an individual has chronic kidney disease, there mostly is no current cure. But early diagnosis and treatment can help prevent kidney failure and the need for a kidney transplant."

Thursday, March 11, is World Kidney Day. To raise awareness, Mayo Clinic will light the Plummer Building in Rochester, Mayo Clinic Hospital in Arizona and the main entrance to Mayo Clinic in Florida orange. Nearly 108,000 people are on the waitlist in the U.S. for a lifesaving kidney transplant, according to the Organ Procurement and Transplantation Network.

Kidneys play a critical role in the body, filtering waste and excess fluid from the body, which are excreted in urine. Chronic kidney disease describes the gradual loss of kidney function.

Below are some key facts to know about chronic kidney disease:

• Some racial and ethnic populations are at higher risk for kidney disease.
  African Americans, Hispanics, Asian Americans and Native Americans are more likely to develop chronic kidney disease. For example, African Americans are three times more likely to have kidney failure, according to the National Kidney Foundation.
  
• Women are more likely to experience kidney failure.
  Chronic kidney disease is more common in women than men, with an estimated 15% of women being diagnosed with it versus 12% of men, according to the Centers for Disease Control and Prevention.
  
• Diabetes, high blood pressure and obesity are key risk factors.
  People with diabetes and high blood pressure, and those who are obese, are all at higher risk for developing chronic kidney disease. Other risk factors include smoking, heart disease, a family history of the disease, older age and abnormal kidney structure.
  
• There may be few signs and symptoms in early stages of chronic kidney disease.
  Symptoms can include nausea, vomiting, loss of appetite, fatigue, sleep problems and changes in urine output. Sometimes people experience shortness of breath, swelling of feet and ankles, muscle twitches and cramps, persistent itching and chest pain.
  
• Quitting smoking and losing weight can help prevent kidney disease.
  Smoking can damage the kidneys and worsen existing kidney damage. Maintaining a healthy weight also can help reduce the risk for kidney disease. It is also critical that people manage chronic conditions such as high blood pressure and diabetes.

Sandra Herrmann, M.D., a Mayo Clinic nephrologist, has a key piece of advice for people at high risk of developing chronic kidney disease.

"Don't wait to talk to your doctor about kidney health," Dr. Herrmann says. "There are simple blood and urine tests that can detect chronic kidney disease. The earlier chronic kidney disease is diagnosed, the better the chance of preventing kidney failure and reducing the risk of other complications such as heart attacks and strokes."

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Heather Carlson Kehren, Mayo Clinic Public Affairs, newsbureau@mayo.edu

The post Expert Alert: Risk for chronic kidney disease even more critical due to COVID-19 pandemic appeared first on Mayo Clinic News Network.

On the Mayo Clinic Radio podcast, Dr. Christopher Aakre, an internal medicine specialist in Mayo Clinic's Fibromyalgia and Chronic Fatigue Clinic, discusses diagnosing and managing fibromyalgia. Also on the podcast, Dr. Andrew Bentall, a Mayo Clinic nephrologist, explains what can be done to help sensitized transplant patients who can be difficult to match with organ donors. And Dr. Victor Karpyak, a Mayo Clinic psychiatrist, shares research on how your genetics can affect your response to treatment for alcohol use disorder. This research is funded by the National Institute on Alcohol Abuse and Alcoholism.

The post #MayoClinicRadio podcast: 3/23/19 appeared first on Mayo Clinic News Network.

On the next Mayo Clinic Radio program, Dr. Christopher Aakre, an internal medicine specialist in Mayo Clinic's Fibromyalgia and Chronic Fatigue Clinic, will discuss diagnosing and managing fibromyalgia. Also on the program, Dr. Andrew Bentall, a Mayo Clinic nephrologist, will explain what can be done to help sensitized transplant patients who can be difficult to match with organ donors. And Dr. Victor Karpyak, a Mayo Clinic psychiatrist, will share research on how your genetics can affect your response to treatment for alcohol use disorder.

Here's your Mayo Clinic Radio podcast.

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Fibromyalgia is a disorder that causes pain all over the body, sleep problems, fatigue, and often emotional and mental distress. Fibromyalgia amplifies painful sensations by affecting the way your brain processes pain signals, meaning people with fibromyalgia are more sensitive to pain than those without the disorder. According to the Centers for Disease Control and Prevention, fibromyalgia affects around 4 million U.S. adults, or about 2 percent of the adult population.

On the next Mayo Clinic Radio program, Dr. Christopher Aakre, an internal medicine specialist in Mayo Clinic's Fibromyalgia and Chronic Fatigue Clinic, will discuss diagnosing and managing fibromyalgia. Also on the program, Dr. Andrew Bentall, a Mayo Clinic nephrologist, will explain what can be done to help sensitized transplant patients who can be difficult to match with organ donors. And Dr. Victor Karpyak, a Mayo Clinic psychiatrist, will share research on how your genetics can affect your response to treatment for alcohol use disorder.

The post Mayo Clinic Radio: Fibromyalgia / sensitized transplant patients / genetics and treatment for alcohol use disorder appeared first on Mayo Clinic News Network.

Watch: The Mayo Clinic Minute

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Please 'Courtesy: Mayo Clinic News Network.' Read the script.

It's one of the biggest hurdles for people needing an organ transplant, and it's caused by their own immune system.

"People can get sensitized from transplantation from previous transplants, from blood transfusions and also from pregnancy," Dr. Bentall says.

He says it happens when a person has antibodies that cause their immune system to reject a transplanted organ.

"The immune system doesn't recognize the organ as an organ," Dr. Bentall explains. "It just says: 'This is foreign. I'm not used to having this in my body, and I'm developed to be able to reject foreign things."

Sensitization can cause a person to wait much longer for an organ transplant.

But researchers have developed drugs that can help protect a transplanted organ in someone whose body is sensitized.

"It stops the antibodies from killing ... the cells there," Dr. Bentall says. "It's a drug that's very effective for that, to be able to let people who either have an unexpected antibody-mediated rejection episode, or one that we may be expecting, to get through that difficult period."

Dr. Bentall says patients with sensitization also do better when they're able to find a living donor. That's because even if they are sensitized to a specific donor's organ, transplant programs often are able to match them to a different living donor and trade one living donor organ for another.

It's a win-win that's only possible when more people decide to be living donors.

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