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Kidney Disease

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This graphic illustrates the mechanisms that occur in kidney disease that leads to a poor protective antibody response against influenza infection and following vaccination. Image prepared using Biorender.com

Fighting off infections when one has chronic disease is a common problem, and during the Covid-19 pandemic that scenario often turned out to be dangerous and deadly. A new study led by Stony Brook Medicine demonstrates that advanced kidney disease compromises the survival of B cells, a type of infection-fighting white blood cell that produces antibodies to kill microbes, and thus significantly reduces the immune response to the influenza virus. The findings are published in Nature Communications.

Comorbid health conditions are critical determinants of immune function. One comorbid condition associated with increased risk of severe infection and infection-related deaths is kidney disease. Infections are the second major cause of death in patients with kidney disease. According to the International Society of Nephrology, an estimated 20 percent of patients with kidney disease die from infection. During the Covid-19 pandemic, mortality rates were as much as 10 times higher for those who had kidney disease compared to those with normal kidney function.

Lead author Partha Biswas, DVM, PhD, a Professor in the Department of Microbiology and Immunology in the Renaissance School of Medicine at Stony Brook University, and colleagues, set out to better understand why those who have kidney disease are unable to mount a protective immune response. The study centered on the condition experienced during kidney disease called uremia – the accumulation of toxic metabolites in the body in the absence of kidney filtration of the blood.

To date clinical studies often show a poor B cell-mediated antibody response after an infection or vaccination in those with kidney disease. Additionally, kidney disease is a known predisposing factor for infection complications, however the reasons are not clear.

“Most studies linking kidney disease with abnormal B cell response were either performed in kidney transplant patients or are corelative in nature. Since kidney transplant patients are immune compromised, it is difficult to assess the impact of kidney disease on B cell response per se,” explains Dr. Biswas.

The researchers used a multiple well-characterized murine model of kidney disease that progresses to renal dysfunction in the subjects. Healthy mice and those with kidney disease were immunized with model immunogens or infected with the influenza virus to trigger a germinal center (GC) response in the spleen, which is central to the development of protective antibody level and infection-fighting response.                                               

They discovered several cellular changes that helps to illustrate the poor immune response in the kidney disease model:

  • Kidney dysfunction leading to accumulation of toxic metabolites triggered cell death in GC B cells leading to poor antibody response during immunization.
  • A previously unidentified role of uremic toxic metabolites hippuric acid (HA) is responsible for increased cell death of GC B cells.
  • HA drove increased death of GC B cells via activating a specific G protein coupled receptor for niacin, which appears to further affect normal B cell response.
  • Kidney disease had negative impact on and inhibits GC and antibody response following influenza virus infection.

According to Dr. Biswas, the paper provides mechanistic insights on how kidney disease negatively impacts protective B cell response infection and immunization. He and his co-investigators believe that the knowledge gained from the laboratory study may shed light on how to generate protective antibody response following vaccination in individuals with kidney disease.

Currently, Dr. Biswas and colleagues are tooling up to use this experimental system to address the apparent lack of response to SARS-CoV 2 vaccination in kidney disease individuals, which may have broader implications for other respiratory virus and bacterial infections seen in these patients.

The research was supported in part by numerous grants from the National Institutes of Health (NIH), including several to Dr. Biswas, grants AI142354, AI162616, AI159058, and AI181831.

Collaborators included scientists from numerous departments and facilities at the University of Pittsburgh, and the Medical College of Georgia.

 

 

 

Credit: Image prepared using Biorender.com

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Kidney health. METRO photo
Walking routinely can reduce your risk of dialysis

By David Dunaief, M.D.

Dr. David Dunaief

Last week, I wrote that 37 million U.S. adults have chronic kidney disease (CKD) and that roughly 90 percent of them don’t know they have it (1).

This seems like a ridiculous number. How can this happen? It’s because CKD tends to be asymptomatic, initially. Only in the advanced stages do symptoms become evident, although there can be vague symptoms in moderate stages such as fatigue, malaise and loss of appetite. Those at highest risk for CKD include patients with diabetes, high blood pressure and those with first-degree relatives who have advanced disease. But those are only the ones at highest risk.

Why is CKD a concern?

Your kidneys function as efficient little blood filters. As I mentioned last week, they remove wastes, toxins and excess fluid from the body. In addition, they play roles in controlling blood pressure, producing red blood cells, maintaining bone health, and regulating natural chemicals in the blood.  

When they’re not operating at full capacity, the consequences can be heart disease, stroke, anemia, infection and depression, among others.

According to the U.S. Preventive Services Task Force and the American College of Physicians, those who are at highest risk should be screened regularly, including patients with diabetes or hypertension (2)(3). 

Fortunately, there are several options available, ranging from preventing CKD with specific exercise to slowing the progression with lifestyle changes and medications.

Does basic exercise help?

The results of a study show that walking reduces the risk of death by 33 percent and the need for dialysis by 21 percent (4).

Those who walked more often saw greater results. So, the participants who walked one-to-two times a week had a 17 percent reduction in death and a 19 percent reduction in kidney replacement therapy, while those who walked at least seven times per week experienced a more impressive 59 percent reduction in death and a 44 percent reduction in the risk of dialysis. There were 6,363 participants with an average age of 70, who were followed for an average of 1.3 years.

How does protein intake affect CKD?

With CKD, more protein is not necessarily better, and it may even be harmful. In a meta-analysis of 17 Cochrane database studies of non-diabetic CKD patients who were not on dialysis, results showed that the risk of progression to end-stage kidney disease, including the need for dialysis or a kidney transplant, was reduced 36 percent in those who consumed a very low-protein diet, rather than a low-protein or a normal protein diet (5).

Should you limit sodium consumption?

Good news! In a study, results showed that a modest sodium reduction in our diet may be sufficient to help prevent proteinuria (protein in the urine) (6). Here, less than 2000 mg per day was shown to be beneficial, something all of us can achieve.

Are some high blood pressure medications better than others?

We routinely give certain medications, ACE inhibitors or ARBs, to patients who have diabetes to protect their kidneys. What about patients who do not have diabetes? ACEs and ARBs are two classes of anti-hypertensives — high blood pressure medications — that work on the kidney systems responsible for blood pressure and water balance (7). Results of a study show that these medications reduced the risk of death significantly in patients with moderate CKD. Most of the patients were considered hypertensive.

However, there was a high discontinuation rate among those taking the medications. If you include the discontinuations and regard them as failures, then all who participated showed a 19 percent reduction in risk of death, which was significant. However, if you exclude discontinuations, the results are much more robust with a 63 percent reduction. To get a more realistic picture, this result, including both participants and dropouts, is probably close to what will occur in clinical practice unless patients are highly motivated.

Should you take NSAIDs?

Non-steroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen and naproxen, have been associated with CKD progression and with kidney injury in those without CKD (1). NSAIDs can also interfere with the effectiveness of ACE inhibitors or ARBs. Talk to your doctor about your prescription NSAIDs and any other over-the-counter medications you are taking.

What should I remember here?

It’s critical to protect your kidneys, especially if you have hypertension, diabetes, or a family history of kidney disease. Fortunately, basic lifestyle modifications can help; lowering sodium modestly, walking frequently, and lowering your protein consumption may all be viable options. Talk to your physician about your medications — both prescription and over-the-counter — and about whether you need regular screening. High-risk patients with hypertension or diabetes should definitely be screened; however, those with vague symptoms of lethargy, aches and pains might benefit, as well.

References:

(1) cdc.gov. (2) uspreventiveservicestaskforce.org (3) aafp.org. (4) Clin J Am Soc Nephrol. 2014;9(7):1183-9. (5) Cochrane Database Syst Rev. 2020;(10):CD001892. (6) Curr Opin Nephrol Hypertens. 2014;23(6):533-540. (7) J Am Coll Cardiol. 2014;63(7):650-658.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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Teresa Orlik, right, with her husband and her son Frank at a recent family event. Photo from Frank Orlik

A Stony Brook man is hoping for a holiday miracle.

Frank Orlik has taken to social media to share his mother’s medical journey. Orlik said he’s been posting about his mother’s search for a kidney donor on Facebook and has been making the posts public with the hope that his connections will share them, and someone will be moved to donate one of their organs.

Teresa Orlik and her son Frank are hoping for a holiday miracle as she waits for a live kidney donor. Photo from Frank Orlik

“This year has been one of so much heartache for me and her,” he said.

His mother, Teresa Orlik, was diagnosed with kidney disease two years ago and recently had to start dialysis. She said the condition runs in her family and was most likely brought on by type 2 diabetes and high blood pressure. Her three sons are unable to donate a kidney since they all have the potential to come down with the disease.

Recently Orlik and her husband sold their house of 46 years in Stony Brook, and they have been living in Palm Coast, Florida, a short distance from the Mayo Clinic in Jacksonville where she is receiving medical treatment.

Dr. Hani Wadei of the Mayo Clinic said when a patient’s kidney function is at or below 20 milliliters per minute, or he or she is on dialysis, a patient can be considered eligible for a transplant.

“We do not have to wait for the kidney function to deteriorate to the point of needing dialysis to get on the transplant waiting list,” Wadei said. “In fact, studies have shown that getting a transplant before starting dialysis is actually better as it improves post-transplant outcomes.”

The doctor said living kidney donors undergo an extensive evaluation which “ensures that a potential donor has a minimal risk of kidney disease after kidney donation.”

The evaluation analyzes potential medical, surgical and psychological complications, and anyone with risks is eliminated, according to Wadei. While a donor may still be at risk for end-stage renal disease, he said recent studies have shown that the possibility after donation is less than 1 percent. The lifetime risk in the healthy population is less than 0.2 percent.

The doctor said he explains to potential donors they can live with one kidney, and they must follow a healthy lifestyle after donation that includes avoiding certain medications, monitoring their health closely and following up with their primary physician. He said after donation the remaining kidney compensates for some of the organ’s function lost from donating the other one.

A donor can live anywhere and have initial blood work and urine testing done by their own doctors and lab services, according to the doctor. However, if they pass initial tests, in the case of Orlik, they must travel to Florida to meet her doctors. A patient’s insurance will usually take care of the donor’s medical expenses for anything involved with the donation, including up to three years of follow-ups.

Frank Orlik said during his mother’s medical crisis he has learned so much about organ donations. For example, he found out about kidney swaps where a living donor is incompatible with the intended recipient, but exchanges kidneys with another donor-recipient pair. Discovering this aspect has made him even more hopeful that his mother will get a kidney.

“I’m praying for a miracle that someone will be able to be a living donor for her,” he said.

Teresa Orlik said her son using social media to spread the word about her search has made her optimistic.

“It gives me tremendous hope that we’ll be successful,” she said.

Anyone interested in helping Teresa Orlik can contact her case coordinator, Tita Bordinger-Herron,  at 904-956-3259.

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Jake Nieto’s research findings have potential to reduce the need for painful kidney biopsies

Dr. Prakash Narayan and Commack High Schoo senior Jake Nieto. Photo from Commack school district.

By Kevin Redding

Most teenagers don’t spend their summer developing new scientific methods that have the potential to revolutionize medical care. But Jake Nieto, a senior at Commack High School, is no ordinary teen.

In 2016, Nieto, a then 15-year-old math and science whiz was looking to spend his summer break continuing research he had gleaned in his chemistry and biology classes. He told his Commack science teacher, Richard Kurtz, who connected him with Dr. Prakash Narayan of Uniondale’s Angion Biomedica Corp., a clinical stage organ restoration company that opens its doors to student researchers.

“He was very precocious. His knowledge and abilities were very advanced for someone his age. If I gave him a problem, it would keep him awake at night.”

— Prakash Narayan

In Angion’s labs, Nieto applied his academic strengths — advanced biophysics, statistical analysis, computation — to an in-depth, months-long project on kidney disease. Despite being the youngest person working at Angion, he often worked four days a week from 8 a.m. to sometimes as late as 5 p.m.

“He was very precocious,” said Narayan, the vice president of preclinical research at Angion. “His knowledge and abilities were very advanced for someone his age. If I gave him a problem, it would keep him awake at night. It’s not like if he couldn’t solve it, he’d let it go.”

Nieto said, as with everything in his life, he was driven by genuine curiosity.

“I just found it so interesting that I could take what I learned from school and finally apply it to actual problems,” he said.

Both of Nieto’s scientific research papers based on that summer’s findings were published by PLOS One, a peer-reviewed, open access scientific journal. The first paper,  published in October 2016, details a formula he came up with and dubbed the “Nieto-Narayan Formula” — that estimates the volume of cysts found in the kidney of a person with polycystic kidney disease.

In a second paper, published this January, Nieto outlined a better approach to determining the amount of scar tissue in the kidney of someone with chronic kidney disease with the aim to alleviate the use of biopsies — the painful process of injecting a long needle through a patient’s back to examine the kidney scarring. For this project, he modified the commonly used elliptical formula in order to obtain more accurate measurements and volume of a kidney.

“I was so excited,” Nieto said. “It was really awesome and humbling to think that something I worked on could potentially be read by other people who are in the field.”

He and Narayan are confident, down the line, that his research has the potential for clinical study and could become part of normal kidney monitoring.

Commack High School teachers Jeanette Collette and Richard Kurtz; Dr. Prakash Narayan, vice president of preclinical research at at Angion Biomedica; and Commack senior Jake Nieto. Photo from Commack school district.

“Jake’s research really opens up the door for noninvasive characterization of kidney disease,” Narayan said. “I believe it can revolutionize the diagnosis and will greatly reduce very painful kidney biopsies. And, of course, for any 15-year-old to walk to spend the summer in a facility here, when other 15-year-olds are doing whatever they’re doing, and achieve this —  I think that’s very remarkable. I’m very proud of him.”

Nieto’s grandfather Ray Ingram, a Queens resident, said he was not in the least bit surprised by this achievement.

“Since he was 4 or 5 years old, Jake was outside looking through a magnifying glass,” Ingram said. “He had a microscope, a telescope, a chemistry set — everything he touched, he took apart and figured out how it worked and figured out a way to improve it.”

At the high school, Nieto is a competitor on the Science Olympiad and mock trial teams. He is president of the Spanish honor society and science honor society, plays trumpet in the marching band, and tutors other students in science and math. While unsure what college he will attend, Nieto knows he wants to study physics and engineering.

When asked if he is ever able to rewire his mind off science, Nieto laughed.

“I try to still have fun and obviously be a normal kid when I’m with my friends,” he said. “But I have my moments where I’ll start looking at something and try to make a scientific connection and be that kind of annoying person. Whenever I see something, I really just want to know why.” 

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Arleen Buckley donated a kidney to her husband of 43 years, Tom Buckley. Photo by Erin Dueñas

By Erin Dueñas

Arleen Buckley ticked off the places she and husband Tom had traveled to before he fell ill. The Port Jefferson couple had visited Italy, Ireland and even China, but a planned trip to Belgium last year had to be canceled after Tom’s battle with polycystic kidney disease — a hereditary condition where cysts develop on the kidneys, leading to the organ’s failure — kept him from traveling.

“He was just too sick,” his wife said. “We were lucky we could get him to the corner.”

Tom Buckley spent months undergoing dialysis three days a week, but the treatments left him weak.

“He wasn’t having a good reaction to the dialysis,” Arleen Buckley said. “I told him we can’t live life like this. It was a tough time.”

Arleen Buckley said she couldn’t bear seeing her husband of 43 years so ill. She suggested giving him one of her kidneys to resolve his health issue but he refused.

“He felt guilty. He didn’t want me putting my life at risk,” she said. “I told him I wanted to live a nice long life — but with him.”

It took months but she eventually convinced her husband to take her kidney, and in September of last year, the couple underwent the surgeries.

Arleen Buckley was up and about just three days later, and while her husband’s recovery took much longer — about six months — he said he feels great. They’re even planning a trip to Scandinavia.

“I couldn’t go anywhere, not even to the movies,” Tom Buckley said. “Now that I’m better I can do whatever I want.”

Last Thursday, April 2, the couple attended the Living Donor Award Ceremony at Stony Brook University Hospital, which honored Arleen Buckley and about 200 other kidney donors. Sponsored by the hospital’s Department of Transplant, kidney recipients presented their living donors with a state medal of honor for the second chance at life.

The ceremony’s keynote speaker was Chris Melz of Huntington Station, who donated a kidney in 2009 to his childhood friend Will Burton, who suffered from end-stage renal failure. The surgeries were successful, and Melz now works with the National Kidney Foundation raising awareness for living donors.

“I want to spark the drive for people to do good,” he said. “Giving is a beautiful thing.”

Arleen Buckley said she was happy to give a kidney to her husband, whom she has known for 50 years.

“I told him, ‘When I was 14 years old, I gave you my heart. At 64, I gave you my kidney,’” the wife said.

Dr. Wayne Waltzer, director of kidney transplantation services and chair of the Department of Urology at Stony Brook University School of Medicine, called kidney transplants a “new lease on life” for patients who are on dialysis.

“Transplants restore them,” Waltzer said. “They get back the same sense of well-being they had before they got sick.”

According to the National Kidney Foundation, 118,000 Americans are on a waiting list for an organ —  96,000 of those wait for a kidney. Roughly 13 people die daily waiting for the organ, the group said.

Stephen Knapik, Stony Brook University’s living donor coordinator, said that every 10 minutes someone in need of a kidney is added to that list. He called it an honor to work with donors who keep the list from growing.

“I’ve never been in a room with so many superheroes in my life,” Knapik said. “The greatest gift you can give isn’t a boat or a car, it’s the gift of life.”

Waltzer said that donating a kidney involves meeting certain criteria including compatible blood groups and matching body tissues between donor and recipient, as well as ensuring that the recipient has no antibodies that will work against the transplanted organ.

While he said the surgery is sophisticated, he called the science and medicine an incredible achievement.

“The immunosuppressive therapy is so good and the medication so effective that you can override any mismatches,” he said.

This allows for donors to give to loved ones that are not related by blood.

With the most active renal transplant program on Long Island, Stony Brook has done 1,500 transplants since 1981. Waltzer said that donors are doing an “amazing service,” not just to their recipient but also to one of the thousands of people who are on the waiting list for a kidney.

“There is a shortage of organs,” he said. “By donating, you are giving a chance to someone else on that waiting list.”

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