From Chicago Tribune, by Jerry Davich
James Myers of Gary poses with U.S. Sen. Joe Donnelly in Washington D.C. on March 16 on behalf of the National Kidney Foundation while advocating for the Living Donor Protection Act. (Handout - James Myers)
James Myers looked weary but cheerful when he returned home from an Indianapolis hospital with his little bundle of joy.
It weighed a quarter of a pound, and was the size of a fist. It's name is "Woody."
"It's a family name," said Myers, 61, of Gary.
After nearly four years of waiting and wondering, Myers finally got the call he had been praying for, hoping for, advocating for. It came on April 26.
At 11 a.m. that day, Myers posted on his Facebook page: "I just got THE call. IU says they have a kidney for me!"
This post was dramatically different from hundreds of previous posts over the past few years, many which read like this one from April 18 of this year: "My name is Jim Myers, from Crown Point, IN, and I am an ESRD patient currently on dialysis, awaiting a transplant. I am on the list. If you are interested in becoming a donor…"
I read dozens of those somber posts, each one pleading for a life-saving transplant amid other social media friends who posted about their pets, chronic gripes or daily errands. I always wondered how Myers felt while reading such nonsense, relatively speaking.
"I am a type O blood type," Myers wrote again and again to friends, followers and strangers. "All medical costs are covered by insurance and incidental costs can be worked out."
When I first met Myers in 2013, he sat quietly in a large chair inside the Fresenius Medical Center in Crown Point. He read a newspaper while his blood was artificially cleansed of waste by a whirring dialysis machine that beeped every few seconds.
With a blanket draped over his legs and a catheter connected to his chest, Myers sat patiently for hours, as most dialysis patients must do. He visited there three times a week for at least four hours each time to undergo hemodialysis, which replaces the function of his failing kidneys.
Myers suffered from polycystic kidney disease, which took the lives of several family members, including his father, he said. Though Myers was diagnosed in his younger days, his positive lifestyle choices the past three decades only delayed the inevitable.
His genetic fate caught up to him in 2012 and he had been on dialysis ever since. "I have no choice. You either submit to dialysis or you die," Myers told me that day. [Read more]
In all of his 44 years, Steve Quantock never knew a time when he wasn’t sick.
Since the age of 2, Quantock has lived with polycystic kidney disease.
According to the Polycystic Kidney Disease Foundation, PKD occurs when “fluid-filled cysts develop and enlarge in both kidneys, eventually leading to kidney failure.”
Men and women, regardless of race and social level, can be diagnosed with PKD.
Although Quantock rebelled against taking care of himself as a teen, as an adult, he became an advocate in the PKD community.
When he was told he needed to start having dialysis, Quantock knew he either had to get a new kidney or PKD would claim his life.
According to the National Kidney Foundation, about 121,000 people a day are waiting for a lifesaving organ transplant, of which 100,000 are waiting specifically for a kidney. NKF also states that 13 people die each day waiting for a kidney transplant.
In Dec. 22, 2015, Quantock received the call that changed his life: A kidney match had been found.
Growing up with PKD
Quantock’s parents discovered he had PKD when he was 2 years old and was so sick that he ended up in Georgetown University Hospital in Washington, D.C., for a month.
“At that time, they were trying to figure out what was wrong,” he said while sitting in his Hagerstown home. “They just kept on doing test after test. And I finally ended up having an exploratory surgery that left me with a 9-inch scar on my belly. When they opened me up to figure out what was going on, they discovered the kidneys had cysts on them. That’s when they discovered it was polycystic kidney disease.”
According to the PKD Foundation, PKD is “is one of the most common, life-threatening genetic diseases.”
And PKD is the fourth-leading cause of kidney failure.
“More than 50 percent of people with PKD will develop kidney failure by age 50,” according to PKD Foundation.
Quantock said there are two types of PKD — dominant and recessive.
“It just so happens to be a genetic mutation in my family, so no one in my family has PKD,” he said. “No one in the past (has it), no one currently, except me. How I got it? Freak of nature.”
According to the PKD Foundation, about 10 percent of those diagnosed with PKD have no family history of the disease, and like Quantock, PKD is developed as a spontaneous mutation.
For Quantock, that meant since the time he was young, his diet had to be watched. He had to be on a low-sodium diet because he had high blood pressure, so he could not eat lunch meats, french fries or other salty foods.
He also couldn’t do the usual roughhousing boys did at his age.
“I couldn’t get hit in the stomach. I couldn’t get into fistfights — what kids do when we were little,” he said. “I couldn’t fall off my bike. Everyday things little boys got into, I couldn’t do. So it was a little strange. I tried to be normal as best I could.”
Quantock admitted that when he got older, he rebelled against the disease.
“I’ve told a lot of people, ‘Nah, I’m not going to be different.’ It was bad enough I had big, bushy red hair and I had a belly and I looked like I was nine months pregnant at 14-15 years old,” he said. “So you can imagine the ridicule I endured. I couldn’t play any contact sports. I couldn’t play football or soccer or anything like that. The only thing I was allowed to play was basketball, and even with that, I was pretty limited to what I could do. My doctors gave me a hard time about it. I played the whole way up until I got up to high school. Then when I got to high school, I stopped playing.” [Read more]
Dan Norcott (right) with Andy Stafford at the Diabetes Center exercise lab in Leicester General Hospital which is also used by The Leicester Kidney Care Appeal's exercise team.
Since his diagnosis at age 21, Dan’s kidney function has deteriorated so later this year his mother Jenny will donate one of her kidneys.
A MAN who is on the verge of receiving a kidney from his mother will set out on an epic 388-mile cycle ride today (Wednesday, May 4) to raise money and awareness for charity.
Dan Norcott, 41, of Wymeswold, has Polycystic Kidney Disease, the same condition that unfortunately led to the death of his father Malcolm in 2004.
Since his diagnosis at age 21, Dan’s kidney function has deteriorated so later this year his mother Jenny will donate one of her kidneys.
But before the transplant, Dan wanted to set himself a challenge.
So today, himself and friends Rich Moss and Andy Stafford will set off from Wymeswold Primary School and begin their 10-day journey to Paris.
The group are raising money for The Leicester Kidney Care Appeal and donations totalling more than £6,700 have already been received on their online JustGiving page.
And to raise awareness of their fund-raising efforts, Dan has even created a comic strip with the help of Terry Wiley which tells his story.
Dan told the Echo: “Training is going well - I’m going 18-20 miles a day and getting fitter all the time.
“I remember my dad cycling around the coast of England and since then I have always wanted to go on a big bike ride.
“This challenge is about raising money to help develop treatments and therapies. Without this transplant, which comes on the back of previous breakthroughs, I’d be dead by 43.
“The most important things I want to get across are:
• If you’re ill, especially with kidney failure, you can still do exercise - unless your doctors tell you otherwise;
• If you don’t think you’re as fit as all those people you see doing exercise, it doesn’t matter - just do what you can and you’ll surprise yourself;
• If you do do exercise, you’ll fell less ill, be happier, and any operations you need are more likely to go well;
• Kidney transplants are way way way better than dialysis, because dialysis makes you feel like hell, and causes heart problems - so register to become an organ donor.”
Polycystic kidney disease is a genetic disorder characterised by the growth of numerous cysts in the kidneys. Dan, who lives with his wife Ali and son Arthur, was diagnosed with the condition aged 21.
The Leicester Kidney Care Appeal charity is funding vital research enabling more answers to be found to better support people with kidney disease.
To keep up-to-date with the team’s progress and donate, visit:http://pedallingtoparis.com/blog/
Transplant Issues
BOSTON -- Patients with autosomal dominant polycystic kidney disease (ADPKD) seem more likely to develop new-onset diabetes after transplantation, researchers reported here.
Based on a meta-analysis of data from 12 separate studies, the risk ratio of new-onset diabetes after transplantation was 1.92 (95% CI 1.36-2.70), according to Wisit Cheungpasitporn, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.
However, some of the included studies did not control for confounders, the authors noted in a poster presentation at the National Kidney Foundation meeting.
When those studies were excluded, the pooled RR was 1.98 (95% CI, 1.33-2.94), they reported.
The authors also pooled three studies to look at the relationship between ADPKD and risk of requiring insulin treatment new-onset diabetes after transplantation, but found that the association was not significant (RR 1.57, 95% CI 0.75-3.27).
"The findings of this study may impact clinical management and follow-up for ADPKD patients after kidney transplantation," they wrote.
They explained that evidence for the link between ADPKD and new-onset diabetes after transplantation has been conflicting, but the incidence of new-onset diabetes after transplantation in these patients is on the rise, range from 7% to 46%.
"It has been proposed that insulin resistance genes co-transmitted with polycystic kidney disease 1 and polycystic kidney disease 2 mutations may interfere with insulin secretion and hepatic gluconeogenesis," they wrote. In addition, evidence suggests that ADPKD patients with normal kidney function have increased insulin resistance.
The analysis comprised 1,379 patients with ADPKD and a total of 9,849 patients who had undergone kidney transplantation. Only studies that reported relative risks, odd ratios, or hazard ratios for the risk of new-onset diabetes after transplantation for patients with ADPKD were included. The risk ratios in the analysis were determined using a random-effect, generic inverse variance method, the authors explained.
They pointed out that other risk factors for developing diabetes after transplantation include obesity, hepatitis C virus, cytomegalovirus infection, impaired fasting glucose, and ethnicity. In addition, patients using corticosteroids or calcineurin inhibitors also have higher risks. [Read more]
PKD Research
Traditionally, gene therapy efforts have attempted to treat genetic diseases by modifying DNA inside a patient’s body, but it has been a challenge to deliver the genetic material to all the target tissue, let alone to do so safely. But in recent years, advances in gene editing and stem cell research have enabled scientists to correct genetic defects in a patient’s own cells and grow tissue-specific “organoids” in vitro. These mini organs hold promise for modeling disease, screening drugs, and—potentially—replacing defective tissue in patients.
Advances in CRISPR/Cas9 gene-editing have enabled researchers to easily and accurately make genetic modifications to human DNA. Meanwhile, the ability to reprogram cells into induced pluripotent stem cells (iPSCs) and other advances in tissue engineering have enabled scientists to grow a range of different tissues, including mini guts, kidneys, and brains.
“Both the CRISPR technology and organoid technology are relatively recent developments,” Benjamin Freedman of the University of Washington told The Scientist. “Genetics is making it possible now to understand—on an individual basis—where a disease is coming from. Combine that with the ability to go to a specific place that’s causing disease and correct it and put that tissue back into a patient, and you have a really powerful combination of tools.”
Hans Clevers, a molecular geneticist at Utrecht University in the Netherlands, is one pioneer of these efforts. His lab uses adult stem cells from the gut, which, unlike other tissue, are constantly renewed. “Our technique is the only one to directly grow organoids from [patients’] tissue,” without having to first convert the cells to iPSCs,” he told The Scientist.
In a 2013 study, Clevers and his colleagues cultured intestinal stem cells from patients with cystic fibrosis. The condition is caused by a defect in the cystic fibrosis transmembrane conductor receptor (CFTR) gene, which leads to a build-up of thick mucus in the pulmonary and gastrointestinal tracts.
In organoids grown from of healthy individuals, adding a substance called forskolin led the tissue to swell, whereas it did not have this effect in organoids grown from patients with cystic fibrosis, Clevers’s team found. Next, the researchers corrected the defect in cells from the cystic fibrosis patients using CRISPR/Cas9 and homologous recombination, and grew the resulting cells into mini guts. Unlike tissues grown from untreated cystic fibrosis patient cells, the CRISPR-modified organoids swelled up normally in response to the addition of forskolin.
But Clevers’s work isn’t confined to modeling simple genetic diseases. In a 2015 study, he and his colleagues used CRISPR on intestinal stem cells to introduce mutations in several genes linked to colon cancer (APC, P53, KRAS, and SMAD4), and cultured the tweaked cells into organoids. When the researchers transplanted the organoids into mice, the tissue developed into tumors that resembled invasive carcinoma.
Meantime, Sara Howden of the Murdoch Childrens Research Institute in Australia and her colleagues are using CRISPR to develop kidney organoid models. “It’s not a full organ, but it’s a lot more relevant than a flat, 2-D culture of cells,” Howden told The Scientist. “That’s the way field is going.”
Organoid models could be useful for screening candidate drugs, at a scale that’s impossible in human clinical trials or even animal models. Because diseases affect each person differently, this approach could allow scientists to figure out which drugs have the greatest chance success in a particular patient.
Further down the road, it may even be possible to take organoids grown from patient cells that have been edited to correct genetic defects, and re-implant them into the patient to treat diseases like cystic fibrosis.
Washington’s Freedman and his colleagues have developed a way to grow kidney organoids from patient-derived iPSCs, which they use to study diseases like polycystic kidney disease (PKD), which causes balloon-like cysts to grow on kidneys, displacing healthy tissue. His lab uses CRISPR to introduce PKD-associated mutations into kidney cells in vitro, and then grows the cells into kidney organoids that form the cysts characteristic of the disease. [Read more]
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