PKD Gift of Life: Starbucks; Effects of Coffee on PKD, Australia Lists Jinarc (Tolvaptan)

PKD Treatment

From The Pharma Letter

Australia to list Jinarc on PBS

The Australian government will list a new medicine for adults with genetic kidney disease on the Pharmaceutical Benefits Scheme (PBS), saving patients around A$23,000 ($16,428) a year.

Jinarc (tolvaptan), which was developed and is marketed by Japanese drugmaker Otsuka Pharmaceutical’s (TYO: 4768), will be available through the PBS from January 1, 2019. It is the first effective drug treatment for autosomal dominant polycystic kidney disease (ADPKD) on the PBS.

The disease is a genetic, progressive and painful disease in which cysts develop and grow in the kidneys. Most people with this disease will need dialysis or a transplant by the time they are 60. There are also multiple complications from the disease, which may include hypertension, chronic and acute pain, repeated urinary tract infections, and depression as the cysts grow and quality of life declines.

The PBS listing of Jinarc provides new hope to people diagnosed with this disease that they may be able to have a better quality of life, with potential for improvement for their kidney and overall health.

Around 900 patients each year are expected to benefit from the listing. Instead of A$23,600 per year they will be able to obtain this innovative new medicine for just A$40.30 per script, or A$6.50 for concessional patients. While 10,000 Australians are estimated to have the disease, most are not diagnosed until the disease is advanced.




Gift of Life

From Time Magazine, By MELISSA LOCKER
How a Starbucks Barista Helped a Customer Find a New Kidney

Sometimes a Starbucks barista has something to more offer than a Frappuccinoand a smile.

Nicole McNeil, a barista at the DuPont, Wash., Starbucks knew something was going on with long-time customer Vince Villano when he seemed down during his trips to her store..

So she she sat down with him and asked him what was wrong, KIRO-TV reports. Turns out, Villano, an Army veteran, needed a new kidney. He was suffering from polycystic kidney disease – his kidneys were only functioning at about 4% – and he was facing a life on dialysis. The debilitating condition has no treatment and the only option is a kidney transplant.

The story stuck with McNeil, who went home and shared the heart-breaking tale with her husband, Justin McNeil. The story struck a chord with Justin, too, and he ultimately decided to donate a kidney to Villano. “I said, ‘I’ve got a kidney, you know, we could do this. I think I’m willing to do that,’” Justin McNeil told KIRO. “It didn’t take long.”

The couple gave Villano the news and as they embarked on the long journey of medical testing to confirm the donation would work, the three struck up a close friendship. Villano and Justin McNeil, who is also an Army veteran, spent months traveling back and forth from DuPont, which is between Olympia and Tacoma in Washington State, to the University of Washington Medical Center in Seattle.

“In general, having them as friends, family, I wouldn’t want it to not be this way. I can’t imagine not having them in my life,” Villano told KIRO.

Both Villano and Justin McNeil had their surgeries on Wednesday and, according to an update posted by Starbucks, “The doctors told [Nicole McNeil] the kidney Justin McNeil donated to Villano looks great, and a post-surgery ultrasound confirmed it is functioning well.”

Living with PKD

From BMC Nephrology

Relationship between caffeine intake and autosomal dominant polycystic kidney disease progression: a retrospective analysis using the CRISP cohort

Abstract

Background

Caffeine has been proposed, based on in vitro cultured cell studies, to accelerate progression of autosomal dominant polycystic kidney disease (ADPKD) by increasing kidney size. Since ADPKD patients are advised to minimize caffeine intake, we investigated the effect of caffeine on disease progression in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP), a prospective, observational cohort study.

Methods

Our study included 239 patients (mean age = 32.3 ± 8.9 ys; 188 caffeine consumers) with a median follow-up time of 12.5 years. Caffeine intake reported at baseline was dichotomized (any vs. none). Linear mixed models, unadjusted and adjusted for age, race, sex, BMI, smoking, hypertension, genetics and time, were used to model height-adjusted total kidney volume (htTKV) and iothalamate clearance (mGFR). Cox proportional hazards models and Kaplan-Meier plots examined the effect of caffeine on time to ESRD or death.

Results

Caffeine-by-time was statistically significant when modeling ln(htTKV) in unadjusted and adjusted models (p <  0.01) indicating that caffeine consumers had slightly faster kidney growth (by 0.6% per year), but htTKV remained smaller from baseline throughout the study. Caffeine consumption was not associated with a difference in mGFR, or in the time to ESRD or death (p > 0.05). Moreover the results were similar when outcomes were modeled as a function of caffeine dose.

Conclusion

We conclude that caffeine does not have a significant detrimental effect on disease progression in ADPKD.

PKD Treatment: Concern for New Medicare Policy, Lixivaptan in Phase 2 Testing

PKD Treatment Policy

From Commercial Appeal, Karyn Waxman, Guest columnist

New Medicare policy will harm patients like me | Opinion

Every day, 12.5 million Americans struggle with polycystic kidney disease, a disease that causes numerous cysts to grow in the kidneys, slowly reducing kidney functionality and possibly leading to kidney failure. I am one of them.

As the Memphis chapter founder and coordinator for the PKD Foundation, I work to help provide a forum for patients who want to find treatments and cure this disease.

That’s why I was alarmed by the Centers for Medicare and Medicaid Services’ new Medicare Advantage Part B step therapy policy, which would begin implementation next year.

Under step therapy, or “fail first,” health insurers require patients to use more cost-effective drugs before using more complex drugs, if the first drug doesn’t work. While this method may work for other parts of Medicare where generic and name brand drugs are indistinguishable, Medicare Part B drugs are not compatible with step therapy drugs.

Part B covers treatment for many serious conditions like PKD and relies on treatment that is tailored to the biology of each patient.

If health insurers forced doctors to prescribe less effective Part B treatments in the name of cost cutting, their zeal for cutting corners may backfire, leading to an increase in visits to the emergency room by Medicare Part B patients who respond poorly to the less effective treatment. As a result, the cost of treatment would rise exponentially, impacting the entire health care system and increasing costs for consumers.

This method also violates the trusted relationship between a doctor and patient. Doctors who treat patients with PKD often forge relationships with those patients that last years, forming a partnership to find the right combination of drugs that will allow each patient to manage their condition and retain a normal quality of life.


When an insurance company steps in on this years-long process in order to dictate which drugs it will allow, it throws years of hard work and collaboration out the window, jeopardizing both the doctor-patient relationship and the health of the patient.

This issue is incredibly personal for me. As someone who struggles with PKD, I anticipate undergoing a kidney transplant from a living donor in the next year. In order to make sure my body doesn’t reject the kidney, I’ll need to undergo a specific regimen of medications, tailored to my own body, for the rest of my life. I’ll be immunosuppressed, meaning I’ll be more susceptible to infections and certain types of cancer.

I can’t afford to “fail first,” or to gamble with drugs that an insurance company might choose for me based off of their own bottom line. This backwards approach takes away the rights of the doctor and the patient, and too often leads to increase in costs on the entire healthcare system.

Patients who battle PKD require timely care and should be permitted to opt out of step therapy, if their health or financial situations change. We simply can’t afford to try a cheaper, riskier treatment for a prolonged period with little success when there is an existing treatment that works. While health insurance companies want to pinch pennies, ultimately, we are the ones who may pay the price.

Sen. Lamar Alexander has been a champion for improving access to health care in this country. He understands that patients deserve to be taken seriously, and a doctor’s expertise should not be overrun by the will of an insurance company. That is why I urge Sen. Alexander to stand up for patients and doctors’ rights and reverse this harmful policy.

Karyn Waxman is the Memphis chapter founder and coordinator for the PKD Foundation.

From Business Wire

Palladio Biosciences Announces Dosing of First Patients with Lixivaptan in ELiSA, a Phase 2 Clinical Study in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Palladio Biosciences, Inc. (Palladio) http://palladiobio.com/, a privately held biopharmaceutical company founded to develop medicines that make a meaningful impact on the lives of patients with orphan diseases of the kidney, today announces the dosing of the first patients with lixivaptan in ELiSA, a phase 2 clinical study in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).

The ELiSA study (Evaluation of Lixivaptan in Subjects with ADPKD), which is being conducted at several clinical sites in the United States, will look at how well two different doses of lixivaptan work in preserving kidney function. It will also look at how well adult subjects with ADPKD tolerate the study drug, which will be given by mouth for 7 days. The study is enrolling male or female ADPKD patients between 18 and 60 years of age and estimated Glomerular Filtration Rate (eGFR) greater than 30 mL/min/1.73m2. Completion of the ELiSA study will pave the way for the initiation of a Phase 3 registration study in 2019.

“Dosing the first ADPKD patients with lixivaptan is a major milestone for Palladio Biosciences,” said Lorenzo Pellegrini, CEO of Palladio. “The ELiSA Study is a key component of our clinical development program and will be used to inform the design of our upcoming pivotal Phase 3 study. We believe that lixivaptan has the potential to meet some of the many unmet medical needs of ADPKD patients.”

David Baron, Chief Scientific Officer of the PKD Foundation, said, “PKD is part of America’s under-recognized kidney disease epidemic. We at the PKD Foundation continue to support the development of new drug therapies for patients with PKD, in part by increasing awareness of PKD clinical studies. We look forward to seeing results of the ELiSA trial and the continued development of lixivaptan for ADPKD.”

To learn more about the trial, visit the Clinicaltrials.gov website at https://www.clinicaltrials.gov/ct2/show/study/NCT03487913.Additional details can also be found at http://palladiobio.com/clinical-trials/ and https://pkdcure.org/clinical-study/elisa-evaluation-lixivaptan-subjects-adpkd/.

About Lixivaptan:

Lixivaptan was granted Investigational New Drug (IND) clearance to proceed with a Phase 2 clinical trial of lixivaptan capsules in patients with ADPKD in the first half of 2018. It had previously received orphan designation by FDA for the treatment of ADPKD. It is a potent, selective vasopressin V2 receptor antagonist, a mechanism of action that has clinical proof of concept to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Lixivaptan was previously administered to more than 1,600 subjects across 36 clinical studies as part of a prior clinical development program for the treatment of hyponatremia. Palladio expects to leverage lixivaptan’s large body of data generated in the hyponatremia clinical program to accelerate the development of lixivaptan for the treatment of ADPKD.

About Polycystic Kidney Disease (PKD) – Key Facts and Figures:

PKD is an inherited genetic disease that affects thousands of people in the United States and millions globally. ADPKD is the most common type of PKD. A person with ADPKD has a 50 percent chance of passing the disease on to each of his or her children. The disease is characterized by uncontrolled growth of fluid-filled cysts in the kidney, which can each grow to be as large as a football. Symptoms often include kidney infections and chronic pain. The continued enlargement of cysts and replacement of normal kidney tissue causes irreversible loss of renal function. In the United States, approximately 2,500 new people with PKD require dialysis or a kidney transplant every year, making PKD the 4th leading cause of kidney failure. There is no cure for PKD.

About Palladio Biosciences, Inc.:

Palladio Biosciences is a privately-owned, clinical stage biopharmaceutical company developing medicines for orphan diseases of the kidney and is located in Newtown, PA. For more information, please visit www.palladiobio.com.

About the PKD Foundation:

The PKD Foundation is the only organization in the U.S. solely dedicated to finding treatments and a cure for PKD to improve the lives of those it affects.

Our vision is to #endPKD. To learn more about PKD, please visit the PKD Foundation website: https://pkdcure.org/resources/category/advocacy/#

Please note that lixivaptan is for investigational use only.

Contacts
Palladio Biosciences, Inc.
Linda Hogan, +1 908-294-8728
lhogan@palladiobio.com

PKD Research: Gene Therapy, Gift of Life: Life Changing Phone Call

PKD Research: Gene Therapy

iNews, United Kingdom, by Tom Bawden

Why are cure for obesity could be on the horizon

A cure for severe obesity could be on the horizon after scientists used a new kind of gene therapy to stop mice getting fat. They say the same technique could potentially be used to treat some cases of epilepsy, cancer, kidney disease and mental and physical developmental delays in children – although it is likely to be around a decade before any are adopted by the health service. Many cases of severe obesity in mice and in humans are driven by a genetic defect which leaves afflicted individuals with an insatiable appetite. This means that they keep on eating and become very overweight.

New technique

Now, scientists have found a way to correct that defect, putting a brake on consumption after a reasonable amount of food has been eaten. Mice with corrected versions of the mutated genes were up to 40 per cent lighter than their untreated counterparts and the effects were long lasting, they found. “The results were dramatic. This technique provides a potential cure for certain forms of obesity as well as hundreds of other diseases such as epilepsy, developmental delay, cancer and polycystic kidney disease,” said lead researcher Navneet Matharu, of the University of California in San Francisco.

The technique could also potentially be used to treat prostate, breast, colon, ovarian and lung cancer, as well as Parkinson’s and inflammatory bowel disease, he said. Severe obesity – where your body mass index is 40 or higher – is one of numerous diseases that can be caused by a mutation in one of the two copies we have of every gene, one from each parent. That dysfunctional gene leaves the second copy to do all the work – which it may not be strong enough to do on its own. In the case of severe obesity, the disease can be caused by a mutation of the gene that regulates hunger or of the gene that regulates satiety.

Pumping up the volume

This treatment worked by ‘turning up the volume’ of the remaining functional gene so that it can do its job effectively. This was done by taking one of the functional copies of the gene, boosting it to amplify its power and then inserting it into the hunger-control regions of the brains of mice by injecting it in a virus that has been rendered harmless.

The researchers are confident that the same technique can be applied to numerous other diseases where a mutation in just one copy of the gene – known as haploinsufficiency – can lead to diseases. “We believe our system could be applied to any situation in which having only one functional copy of a gene leads to disease. Our method demonstrates tremendous therapeutic potential for numerous diseases,” said Dr Matharu. Sometimes the mutation is a fairly minor cause of a disease and in others it can be the primary cause, researchers said. They point out that at least 660 genes – and potentially more than 3,000 – human genes are haploinsufficient, acting as a cause hundreds of diseases. The research is published in the journal Science.

ANALYSIS

It’s still early days but this obesity breakthrough in mice could have the potential to revolutionise the healthcare system for humans. Assuming that the new gene therapy technique also keeps down the weight in humans, it has the potential to significantly cut cases of severe obesity – which lead to numerous health problems and often early death. It also costs the NHS a fortune to treat the associated diseases. Ultimately, despite the potential to avert early death, medics and patients may baulk at the prospect of an injection to the brain to cure obesity. Time will tell on that one. But there are other cases where an injection to the brain would be well worth it – with extreme epilepsy being an obvious example.

Gift of Life

From Woodward News, Woodward, OK, By Elise Solloway Area Correspondent

The life-changing phone call: The generosity of a friend and a successful surgery

Kidney donor Randy Arrington and recipient Elise Solloway, Oct. 30, 2018 (one day after the transplant surgeries).

Editor's Note: Elise Solloway is a correspondent for the Woodward News. She recently received a kidney transplant after fighting a genetic kidney disease. She underwent successful transplant surgery in October and is telling her story this week in the Woodward News.

After finding a donor and being accepted for the transplant, the NZTI staff wanted us both to come to Oklahoma City the very next day to get pre-registered for surgery at Integris Baptist Medical Center, get pre-op lab and EKGs done, get surgery preps at the pharmacy, and for me to get my first batch of immunosuppressant (anti-rejection) medications to take in preparation for the surgery so my body would not reject Randy’s kidney.

Weeks of prayers by family, friends, and my church family were answered. In just a few months, I went from being a patient on the national and NZTI kidney transplant list to being scheduled to have a transplant from a healthy, generous, living donor who responded to my Facebook posts.

Having been a chronic worrier most of my life and dealing with many health problems over the years, I learned as an adult to put things in perspective when approaching life’s challenges. None of my previous fears had ever come true, so I gradually learned to not worry, just put things in God’s hands and leave them there.

After reading the pros and cons of a kidney transplant vs dialysis, and all the potential side effects of the various anti-rejection drugs and steroids, I simply entrusted it all to God. I pledged not to be a worrier.

On Monday, October 29, 2018, Randy underwent surgery to safely remove his healthy right kidney which was then transplanted into the left side of my abdomen to replace my two kidneys with advanced Polycystic Kidney Disease. We each spent four days on the 10th floor of Integris Baptist Medical Center where we received exceptionally good care.

Randy and I visited each other’s rooms and walked laps together on our floor beginning the day after our transplant surgeries. On our walks we also met another transplant patient and sometimes all three of us were walking laps and chatting in the hall.

While in the hospital I received about five hours of education related to warning signs of organ rejection, what each of my medications were for, and how to follow the daily schedule for taking the medications and recording my vitals. I also received information on what foods were safe and which ones were not safe to eat due to my new kidney and my various medications.

One day my surgeon asked if I had any children and if they had been tested for PKD. A new medicine approved by FDA has proven to slow down or even stop the progression of PKD and our son would need to start it as soon as possible.

My husband called our son to encourage him to get tested and start the medication. He was surprised to find out he had been tested 2-3 months ago and had no sign of PKD. He just had not notified us for some reason.

Because he did not inherit PKD from me, his children could not inherit it from him. We were overjoyed with relief. PKD ends with me and my sister in our family.

Since coming home from the hospital, Randy and I keep in touch via telephone and the Internet. We are both recovering nicely from our transplant surgeries. He will go back to work Dec. 10.

Randy is literally a part of my life now, and always will be. He gave me the gift of life by the ultimate gift of one of his healthy kidneys to replace my seriously diseased kidneys. I am eternally indebted to him and thankful to God for this gift.

For the rest of my life I will have a medically-necessary schedule to follow. I now live from 8 a.m. to 8 p.m. with a to-do list of medically necessary procedures. Every 8 a.m. I must monitor my weight, temperature, blood pressure, fluid in-take and out-put, and take multiple medications necessary to keep my new kidney working well so it will not be rejected by my body. Then at 8 p.m. I do some of the same things all over again. I must follow this schedule, even when traveling, by pulling over on the side of the road to record my vitals and take my medications at the designated times.

Everywhere I go I must take with me my backpack that contains my daily health log, all my medications sorted in an organizer, a thermometer, a blood pressure machine. It must also include my3-ring binder filled with my medical exam/lab summaries with diagnoses and medication/diet changes based on the lab work results.

For awhile, I will have weekly lab work drawn to monitor my new kidney’s function and my general health, then meet with my medical team to monitor the healing of my incision, then adjust medications and diet as needed. As my system stabilizes with the new kidney, medications will be reduced, but there will always be one or more immunosuppressants/anti-rejection medications to take.

Extra precautions are now necessary everywhere I go and whenever I am around other people. Hand sanitation and/or gloves plus face masks are necessary in some settings to reduce the chances of me catching a virus, infection, or bacteria since I have a weakened immune system and could have an organ rejection.

I must limit my exposure to cats, animal feces, reptiles, ponds, mulch, certain foods, and anyone who has had a live culture immunization within three weeks. Anytime I am exposed to sunlight I must wear sun-blocking clothes, sun screen, and wear a sun-blocking hat, due to my risk of skin cancers from the transplant medications I take. I must also watch my diet because I am now at higher risk of getting diabetes due to my transplant medications and medical history.

PKD Life: Family Business; Combat Human Organ Black Market; PKD Fundraising

PKD Life

From 2Paragraphs

The Profit: NYC Bagel Deli Owner Lost 2 Children To PKD Kidney Disease

Corey Kaplan on The Profit (CNBC)

On the Season 6 premiere of The Profit, small business investor Marcus Lemonis visits NYC Bagel Deli, a bagel chain with three locations in downtown Chicago which sells over 1,000 bagels daily. On The Profit, according to CNBC, “the overbearing owner” Corey Kaplan “ignores his wife’s business ideas and hangs on to the outdated look of his cluttered storefronts.” Marcus tries to help Cory re-brand the company and help develop new products. But not a lot of small business owners like change.

While getting to know Corey and his wife Candis, Lemonis learns that the couple had five children but “two of them are in heaven,” says Corey. The two children they lost, Corey and CorriAngel, both died extremely young of PKD, polycystic kidney disease. It is a chronic, genetic disease causing uncontrolled growth of cysts in the kidney, often leading to kidney failure. Lemonis encouraged Corey to change the name of NYC Bagel Deli to Corey’s NYC Bagel Deli in honor of his children.

After filming The Profit, Corey Kaplan wrote of Lemonis’ huge heart and “the fact that he is helping us bring awareness to PKD (the disease that our children died from), I will never forget him and his open-hearted kindness.” The Profit airs Tuesdays at 10 pm on CNBC.

Organ Transplants

From Australian Broadcast Corp., By political reporter Stephanie Dalzell

Australian transplant waiting list contributes to human organ black market, committee says

Key Findings:

Committee finds if Government doesn't act, organ market will flourish

About 1,400 Australians waiting for transplant, 11,000 on renal dialysis

Average waiting time for replacement kidney is 3 years


The criminal masterminds behind the illegal trade of human body parts raked in $2.3 billion around the globe last year.

About 12,000 organs were sold on the black market, and while the majority of those exchanges involved kidneys, 654 hearts and 2,615 livers were sold for up to $394,000 each.

That illegal trade will continue to grow if the Australian Government does not do more to deter human organ trafficking, according to a unanimous report handed down by a parliamentary committee.

About 1,400 Australians are currently waiting for an organ transplant, while a further 11,000 are on kidney dialysis, and the committee found if the government failed to address the gap between the number of people requiring organ transplants and the limited supply of freely donated organs, the black market would keep flourishing.

Commercial organ market

Organ	Global illicit transplants (per annum)	Price range (AUD)
Kidney	7,995	$68,000 - $163,000
Liver	2,615	$134,000 - $197,000
Heart	654	$176,000 - $394,000
Lung	469	$203,000 - $394,000
Pancreas	233	$149,000 - $190,000

The chairman of the Human Rights Sub-Committee of the Joint Standing Committee on Foreign Affairs, Defence and Trade, Liberal MP Kevin Andrews, told Parliament the average waiting time for a kidney in Australia was three years.

"Desperate people often facing certain death without a transplant may travel far from their own countries to places such as Egypt, the Philippines or Pakistan, paying tens of thousands of dollars or more, for an organ transplant, where the donor is most likely in dire financial straits, possibly exploited, and unable to give free and informed consent to donation," Mr Andrews said.
Cutting down demand

The committee's report recommended the Australian Government pursue a range of measures to strengthen its involvement in international efforts to combat human organ trafficking, collect data on Australians involved in illegal organ trafficking overseas and also tighten criminal laws around organ harvesting.

It also concluded the Government should seek to improve organ-donation rates through ongoing funding of programs, education awareness campaigns, and the investigation of other international programs — such as opt-out organ donation.

Mr Andrews said the committee heard from many people who argued protections against the practice needed to be strengthened.

PKD Fundraising

From MLive, By Greg Chrapek  chrapek@mlive.com

West Michigan Aviation Academy hosting `Teal Out' basketball game to raise awareness of polycystic kidney disease

The West Michigan Aviation Academy boys basketball team is capping a week of fundraising by the school by hosting a 'Teal Out Night' game against Hopkins this Friday.

The Teal Out event is part of a week-long effort by the students that serves as a fundraiser and awareness activity to end polycystic kidney disease (PKD). Student activities during the week include Penny Wars, t-shirt sales and an auction. Teal is the official color for PKD. East year the students at West Michigan Aviation Academy select a non-profit organization to work with and PKD was chosen as this year's charity.

Speaking at the game even will be Dr. Greg Vanden Heuvel from Western Michigan University and Kim Ahrens, a Detroit PKD representative. The event is taking place to bring awareness of PKD to West Michigan and generate funds for research to find a cure.

Friday's basketball game with Hopkins is schedule for 7 p.m. this at the school located at 5363 44th St. SE.

Giving Tuesday; PKD Treatment: Lanreotide Not Effective; Gift of Life: Warm Hands, Organ Donation Law Update; PKD Research: Cilia

PKD Foundation

Join the PKD Foundation for #GivingTuesday

November 27, 2018

#GivingTuesday is right around the corner, and this year, we’re asking: what can you give?

Can you give a donation? Our goal for #GivingTuedsay is to raise $18,000 — the amount needed to fund ten weeks of PKD research. When you select the PKD Foundation as your organization of choice, you help us keep our momentum going and can help bring treatments to patients faster.

Can you give your voice this season? 

When you raise awareness for PKD, you help others better understand this disease and its impact on families worldwide. You can give your voice this #GivingTuesday by:
Using our custom profile frame
Sharing your story on Voices of PKD
Sharing infographics to educate others


Can you give your time? 

Our PKD community wouldn’t be where it is today with the time selflessly given by patients, caregivers, advocates and volunteers. You can give your time this #GivingTuesday by:
Posting your #UNselfie to share how you plan to give this year
Advocating for PKD patients
Getting involved with your local Chapter

No matter what you give this #GivingTuesday, when you give to the PKD Foundation, you are making a difference in the lives of those in our community. Help us further our mission to give hope by helping us fund research, advocate for patients and build a community for all impacted by polycystic kidney disease (PKD).

PKD Treatment

MDLinx

Effect of lanreotide on kidney function in autosomal dominant polycystic kidney disease

In this randomized clinical trial, researchers examined the efficacy of somatostatin analog lanreotide for slowing the rate of decline in kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD). Outcomes revealed no slowing of kidney function decline with lanreotide administration in patients with later-stage ADPKD.



Methods
Researchers performed an open-label randomized clinical trial with blinded end point assessment at 4 nephrology outpatient clinics in the Netherlands; 309 patients with ADPKD were included from July 2012 to March 2015.

Patients aged 18 to 60 years with an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2 were eligible for inclusion.

In August 2017, follow-up of the 2.5-year trial ended.

They randomly assigned patients to receive either lanreotide (120 mg subcutaneously once every 4 weeks) in addition to standard care (n = 153) or standard care only (target blood pressure <140/90 mm Hg; n = 152).

Annual change in eGFR assessed as slope through eGFR values during the 2.5-year treatment phase was assessed as the primary outcome.

Change in eGFR before vs after treatment, incidence of worsening kidney function (start of dialysis or 30% decrease in eGFR), change in total kidney volume and change in quality of life (range: 1 [not bothered] to 5 [extremely bothered]) were included as secondary outcome measures.

Results
The trial was completed by 261 (85.6%) of 309 randomized patients (mean [SD] age, 48.4 [7.3] years; 53.4% women).

The lanreotide and the control group had annual rate of eGFR decline of −3.53 vs −3.46 mL/min/1.73 m2per year, respectively (difference, −0.08 [95% CI, −0.71 to 0.56]; P=.81).

Researchers noted no marked differences for incidence of worsening kidney function (hazard ratio, 0.87 [95% CI, 0.49 to 1.52]; P=.87), change in eGFR (−3.58 vs −3.45; difference, −0.13 mL/min/1.73 m2 per year [95% CI, −1.76 to 1.50]; P=.88), and change in quality of life (0.05 vs 0.07; difference, −0.03 units per year [95% CI, −0.13 to 0.08]; P=.67).

The lanreotide group displayed lower rate of growth in total kidney volume than the control group (4.15% vs 5.56%; difference, −1.33% per year [95% CI, −2.41% to −0.24%]; P=.02).

The lanreotide vs control group had adverse events including injection site discomfort (32% vs 0.7%), injection site papule (5.9% vs 0%), loose stools (91% vs 6.6%), abdominal discomfort (79% vs 20%), and hepatic cyst infections (5.2% vs 0%).

PKD Research

From PHYS.org

Monitoring real time changes during cell division

Scientist have cast new light on the behaviour of tiny hair-like structures called cilia found on almost every cell in the body.

Cilia play important roles in human development and disease. Akin to tiny antennae, they act as cell timers keeping the brakes on cell division until the right growth cues are received.

Malfunction of cilia leads to many human diseases such as polycystic kidney disease and cancer.

In the study published in Developmental Cell, researchers from the Universities of Edinburgh and Lancaster developed a multi-component fluorescent biosensor that allows users to 'light up' both cilia and cells that are actively dividing simultaneously. This is important because the machinery that drives cilia growth and cell division are shared.

Dr. Pleasantine Mill of the University of Edinburgh said: "This powerful new tool will allow us to investigate cilia function in human disease in unprecedented detail."

Cilia are important in embryonic development shaping the size of organs, like our brains and lungs. However in adults both loss and hyperactivity in these crucial signalling centres is implicated in cancer cell proliferation and migration.

Dr. Richard Mort of Lancaster University said: "It has long been known that the cilia and cell cycles are closely linked but until now it has been difficult to image these processes in parallel."

The new biosensor will allow researchers to carry out fundamental studies exploring how changes to cilia length and dynamics affect the speed of division and of tissue development.

Joint first author Dr. Matthew Ford said: "This new resource will shed light at an individual cell level on the interplay between the cilia and cell cycles in development, regeneration and disease."

It is hoped these studies will help researchers build a more detailed picture of cilia in human disease and help monitor novel therapeutic approaches.

Gift of Life

From The Courier News, Elgin, IL, by Janelle Walker

Warm hands the first sign of new life after kidney transplant, South Elgin man says

The first thing Jeff Speyers noticed when he woke up last Tuesday morning was that his hands felt warm.

In his bed at the University of Wisconsin-Madison Hospital's transplant unit, those warm hands were the first sign the previous night's kidney transplant was already changing his life.

“He was smiling from ear to ear,” his wife, Vicki, said.

Jeff, 60, of South Elgin, waited three years for that transplant. He was diagnosed with polycystic kidney disease — a genetic disorder — at age 45. The disease killed his grandfather, father and brother at young ages so Jeff changed his lifestyle and diet to help slow its progression.


The disorder causes cysts to grow on the kidneys and the stress that places on the body often leads to brain aneurysms, which is what killed his other male family members.

When he was first put on the transplant waiting list, Jeff’s kidneys were functioning at 15 percent each, according to his doctors at the Kovler Organ Transplantation Center at Northwestern Hospital.

At the advice of his Northwestern doctors and with little difference in travel times, he transferred to the Madison hospital. The hope there was for a smaller pool of people awaiting transplants.

Three weeks before the call came, he went to Madison for a checkup. Doctors said his kidney function was down to just 5 percent and either dialysis or a transplant would need to happen by February.

Then, on Nov. 10, the call came.

“They called Saturday at 11 a.m. and said, ‘Get up here by 4 p.m.,’” Vicki said.

“It was more of a shock and the reality of it all came rushing in, that we knew it would happen,” she said.

The Speyers own Hans and Sons Plumbing in South Elgin. Hans was Vicki’s grandfather, and she took the business over from her father. Jeff married into the business. He also serves on the South Elgin and Countryside Fire Protection District Board of Trustees.

Friends in South Elgin held a fundraiser for the couple to cover some treatment costs and missed income — and to publicize Jeff’s need for a kidney donor. The couple never had children so they couldn’t go to a child for a kidney. They also knew that any male children would be at risk of also developing the disorder.

While a few people had made overtures about donating, they were not good matches, the couple said.

They do not know who Jeff’s donor was other than his or her family decided to end life support and allow the organ to be harvested for donation. The kidneys — the other went to another person at the Madison hospital — were helicoptered in from 90 minutes away.

“It is so sad but God bless the person who is the donor. Two lives were saved within hours and that is just from the kidneys. They also had the heart, the lungs, the liver. In the back of my mind, I still think about that family,” Vicki said.

Jeff went into surgery Monday evening. From pre-op to recovery room was just five hours — the new kidney was implanted and his old kidneys remain in place. There is no chance the donated kidney will get the same cysts, and it was an 85 percent match for blood and tissue types, he said.

Still, the couple said from their living room the following Saturday, the kidney is “waking up.”

“It is a sleepy kidney,” which needs to adjust to a new body. Jeff will be on anti-rejection medications for the rest of his life.

As a plumber, Jeff has some understanding of the science.

“It is three pipes you are hooking back up” to connect the kidney to his body, he said with a laugh. A stent from his new kidney to his bladder will also remain in place for three weeks, and Jeff will need to go back to Madison for blood draws and tests twice a week for the next several weeks. Those tests will monitor the new kidney to see if it is working correctly.

There were some immediate changes, like warmer hands and feet. He's still tired but expects to live a full life without worry of further issues as long as there is no organ rejection.

He was back home in South Elgin by Friday night, sitting on the couch where he’d spend much of his weekends for the past few years. Weekends, he said, were the only time he allowed himself to just rest.

The fact that Jeff kept working every day helped his body wait out the time between when a transplant was first suggested and finally getting the surgery, Jeff said.

“My pathologist said my work — physically working, keeping my weight down, not smoking, not drinking, not sitting around” — would help, Jeff said.

“The way Jeff and I look at it, it is a waste of a good day of life moping around and being angry. His attitude, he is the most positive and upbeat person I know,” Vicki said.

Jeff has already outlived the men in his family who died young from the disease, he said. Back when his grandfather and father died from PKD, it was just “kidney disease” and little was known about the why, he said.

“This is best thing that has ever happen to me, outside of marrying Vicki. I am just so thankful,” Jeff said.

From Times Herald, PA, By Dutch Godshalk For Digital First Media

RESTORING LIFE: Donate Life PA Act updates state organ donation law

When Rosalie Hetrick realized it could be years before she’d receive a kidney through the national waiting list, she resolved to take matters into her own hands.

A longtime carrier of polycystic kidney disease, Hetrick, who lives in Norristown, was added to the transplant list in 2015 when her kidney function dropped below 20 percent. Even so, it wasn’t long before her doctor started talking about dialysis.

“I thought the plan was to get a transplant?’” Hetrick asked, confused.

“Not if you don’t look harder for a donor,” her doctor replied. “That may not happen.”

The average wait time for a kidney from the national deceased donor waiting list is five years. Sometimes it’s less, sometimes it’s more. Suffice it to say, someone in Hetrick’s position can never be sure when their number is going to get called.

This real-talk from her doctor gave Hetrick “the boost” she needed to look outside of the list. She asked friends, family, and acquaintances for a kidney. Eventually, “I put it on Facebook,” she said. Where better to issue a widespread call for help?

As luck would have it, a Facebook friend by the name of Ann-Marie Hulstine answered that call and offered a kidney to Hetrick. The transplant operation took place in February.

“When I put it out there, Ann-Marie didn’t hesitate, and she didn’t hesitate during the entire process. It was kismet, or the grace of God,” said Hetrick. “I have not found a way to tell her how grateful I am. I don’t know how you thank somebody for giving you life again.”

Hetrick’s story is inspiring, emotional; it’s a tearjerker about human kindness and life restored. But her story also hints at a growing problem in the U.S. According to government statistics, more than 114,000 Americans are currently on the ever-growing organ transplant waiting list—and they’re dying at rates of roughly 20 per day.

With the recent passage of a new law, state legislators are aiming to tell a different story, one where more people register as organ donors so that fewer people are waiting years for a life-saving transplant (or resorting to a Hail Mary plea on Facebook to find one).

The Donate Life PA Act, which passed unanimously in the House and Senate at the beginning of October, aims to increase the organ donor pool in Pennsylvania, mostly through increased awareness and donor registration opportunities.

For one thing, the new law “provides for all high schools to have access to a model curriculum to teach teenagers about organ donation and transplants,” said Howard M. Nathan, CEO of Gift of Life Donor Program in Philadelphia.

By educating students—grades 9 through 12—the hope is to inspire them to register early on. Students can register to be organ donors when they’re 16 with parental consent.

According to numbers from Gift of Life, Pennsylvania currently has around 4.7 million registered organ donors. Of those millions, Montgomery County has roughly 360,000 donors and Chester County hovers in the area of 231,000, Nathan said.

While these numbers seem large, they can be deceiving.

“Organ donation is a somewhat rare event,” Nathan said. “Less than 2 percent of all people who die in hospital” are medically suitable to have their heart, lung, or kidney transplanted. “And it’s not because people aren’t willing to donate; it’s because the number of people who could be donors is small.”

There are vast criteria for deeming an organ viable for transplantation, including a review of the patient’s medical status, past medical history, and the manner of death. Furthermore, the majority of organs extracted for donation come from patients who have been declared brain dead and are being kept alive through mechanical ventilation.

These many necessary requirements tend to take large donor numbers—like 360,000 in Montgomery County—and whittle them down to slivers.

Last year, the Gift of Life Donor Program had 565 donors, which translated to 1,546 organs transplanted. But if you consider the total number of patients currently waiting for organs in Pennsylvania—around 7,300—“that doesn’t sound like a lot,” Nathan said.

That’s why increasing overall registrants is one of the surest ways of helping patients in need.

“What’s interesting is, when we survey people in general, about 85 percent of the public say they want to be an organ donor,” Nathan said. With about 48 percent signed up in Pennsylvania, that makes for “a gap between the people who sign up and the people who say they want to be donors. We’re trying to make people understand.”

Other provisions under the Donate Life PA Act, which was signed by Gov. Tom Wolf on Oct. 23, include increasing opportunities for adults to register as organ donors. It also ensures a full assessment of organ donation potential by county coroners and health care professionals, with added assurance that any denial of organ donations will be well-documented.

“The coroner has jurisdiction,” Nathan explained. “Even if the individual or family has said yes” to an organ donation, the coroner has authority to deny it. Occasionally, an organ may be turned down for donation due to the needs of a criminal investigation.

“Over the past four years there have been about 40-some turndowns,” said Nathan. The new law “allows procurement organizations to have huddles before the coroner turns it down.”

As lawmakers and advocates continue developing new methods of encouraging Americans to register as organ donors, many patients in need are hedging their bets and taking Rosalie Hetrick’s route. They’re looking for living donors wherever they can. They’re beseeching friends, family members, coworkers, and the nebulous hordes of social media.

When asked her feelings on the Donate Life PA Act, Hetrick said she’s especially in favor of the provisions for access to model curriculum in high schools: “I’m all for anything that brings awareness. The more you can shed light on this, the better.”

PKD Research: Blocking Cyst Growth: Venglustat; Stem Cell Surprises; Kidney Donors: Age No Barrier

PKD Research

From AJMC, by Mary Caffrey

Sanofi Pivotal Trial to Target Driver of Cyst Growth in PKD

Polycystic kidney disease (PKD) affects about 600,000 people in the United States, which accounts for 5% of all cases of kidney failure. Autosomal dominant PKD (ADPKD), which affects about 120,000 people in this country and 170,000 in the European Union, is an especially devastating, painful illness. Propelled by a genetic mutation, ADPKD causes cysts to grow on the kidneys, which become enlarged as the cysts fill with fluid and take over these vital organs.

Normally the size of a fist, a kidney covered by cysts can expand beyond the size of a football and weigh more than 35 pounds. People with this condition experience intense abdominal pain, high blood pressure, infections, and kidney stones, typically starting between age 30 and 40.

ADPKD progresses at different rates in different patients; some will not need dialysis or a kidney transplant until age 70 but others whose disease is rapidly progressing may reach end-stage renal disease (ESRD) in their 50s. Until recently, there were no treatments of PKD; in August, Otsuka Pharmaceutical won approval for tolvaptan (Jynarque), which can slow the loss of kidney function by blocking water reabsorption in the kidney ducts.

But research over the past decade suggests that it’s possible to target the mechanism that triggers the growth of cysts in the first place. Sanofi Genzyme is developing a treatment to do this, and last month announced it is enrolling patients in a pivotal trial for venglustat, an investigational oral therapy that has shown promise in mouse models of blocking the substances that drive tumor growth.1

These substances, called glucosphingolipids (GSLs), are overexpressed in patients across an array of renal diseases, from diabetic nephropathy and renal cell carcinoma, as well as PKD. GSLs are known to regulate many cellular processes, including cell proliferation. A 2010 paper that explored the mechanism of blocking GSLs in mouse models discussed the idea that if the GSL metabolism is sped up, this may boost the growth of cysts in PKD; conversely, blocking this pathway could cause the cysts to stop growing or even retreat.

Describing the possible mechanisms of action in a 2016 paper, James A. Shayman, MD, wrote that so far, the experimental use of inhibitors looks promising in reversing the disease characteristics.2 He writes, that understanding the link between GSL inhibition and “reversal of either renal hypertrophy or cyst growth is more than a scientific exercise.”

This is precisely what researchers hope to see as they recruit the first patients for treatment with venglustat in a clinical trial, said Gianluca Pirozzi, MD, PhD, head of Development for Rare Diseases and the head of Translational Gene Therapy at Sanofi, in an interview with The American Journal of Managed Care®. Pirozzi, who previously led development of dupilumab (Dupixent), which blocks key immune system pathways to treat atopic dermatitis, is optimistic; he said that FDA recognizes the therapy could address an enormous unmet need. Venglustat has received Orphan Drug Designation.

Unlike tolvaptan, which Pirozzi said will relieve symptoms of rapidly progressing PKD, venglustat aims to disrupt the disease mechanism itself. If the treatment works as Sanofi hopes, the key will be to identify the 30% of PKD patients who are “rapid progressors,” whose kidney function is declining at a comparatively young age and who face years of dialysis or early death from the disease. ESRD treatment costs are rising faster than others in healthcare, to at least $90,000 per year. Those diagnosed with ESRD before age 65 become eligible for Medicare because treatment is so expensive.

Thus, for affected patients, the prospect of halting cyst growth by taking a pill once a day, “could be life changing,” Pirozzi said.

Because venglustat would need to be taken daily for the rest of a patient’s life, targeting the right population will be a major point of discussion with payers, he said.

“We need to find ways to identify who are the right patients, the fast progressors,” Pirozzi said. His recommendation would be to start treatment, “as soon as possible.”

From MedicalXpress

Brain, muscle cells found lurking in kidney organoids grown in lab

Scientists hoping to develop better treatments for kidney disease have turned their attention to growing clusters of kidney cells in the lab. One day, so-called organoids—grown from human stem cells—may help repair damaged kidneys in people or be used to test drugs developed to fight kidney disease.

But new research from Washington University School of Medicine in St. Louis has identified rogue cells—namely brain and muscle cells—lurking within kidney organoids. Such cells make up only 10 to 20 percent of an organoid's cells, the scientists found, but their presence indicates that the "recipes" used to coax stem cells into becoming kidney cells inadvertently are churning out other cell types.

While at first glance the discovery might be viewed as a setback for using kidney organoids as stand-ins for human kidneys, there's still promise. The researchers found an easy way to prevent most of those wayward cells from forming, and that same approach could be adopted by other scientists who find rogue cells in other organoids, such as those of the brain, lung or heart.

The research is published Nov. 15 in Cell Stem Cell.

"There's a lot of enthusiasm for growing organoids as models for diseases that affect people," said senior author Benjamin D. Humphreys, MD, Ph.D., director of the Division of Nephrology. "But scientists haven't fully appreciated that some of the cells that make up those organoids may not mimic what we would find in people. The good news is that with a simple intervention, we could block most of ­­the rogue cells from growing. This should really accelerate our progress in making organoids better models for human kidney disease and drug discovery, and the same technique could be applied to targeting rogue cells in other organoids."

A major reason for the excitement around kidney organoids is the challenge of caring of patients with kidney failure. In the United States alone, nearly 500,000 people receive dialysis for end-stage kidney disease.

"Developing kidney organoids is driven by the reality that we have so many patients with failing kidneys and no effective drugs to offer them," said Humphreys, who is also the Joseph Friedman Professor of Renal Diseases in Medicine.

For the current study, the researchers looked at two recipes widely used by scientists worldwide to grow kidney organoids. One starts with embryonic stem cells approved for research by the National Institutes of Health (NIH), and the other begins with induced pluripotent stem cells, which are reprogrammed from adult cells and have the ability to develop into any type of human cell.

A cocktail of drugs and growth factors are added to the stem cells, channeling their development into kidney cells. After growing the organoids in the lab for four weeks, a time frame long enough for the cells to specialize, the researchers asked: What kinds of cells did we get?

Rather than conduct a spot check to identify cells that made up the organoids, the researchers relied on a relatively new technique to take a deep dive. Using single cell RNA sequencing, they analyzed the activity of many thousands of genes in 83,130 cells from 65 kidney organoids.

"This generates massive amounts of data, and there's no way our brains can make sense of it all," Humphreys explained. "But computers can easily compare gene activity across 83,000 cells and, using artificial intelligence, group cell types together based on their gene expression. So rather than looking for cells that we think we thought we'd find in the organoid, it helped us find cells even if we'd never imagined they'd be there."

Regardless of the recipe, the researchers found that 10 to 20 percent of the cells in the organoids missed the cue to develop into kidney cells and instead became brain and muscle cells. However, by reconstructing the step-by-step process by which stem cells developed into brain cells, for example, they were able to see precisely where things went off the rails and block the formation of off-target cells. This reduced the number of brain cells by 90 percent, and the approach provides a road map to help other scientists eliminate rogue cells in other types of organoids.

"Progress to develop better treatments for kidney disease is slow because we lack good models," Humphreys said. "We rely on mice and rats, and they are not little humans. There are many examples of drugs that have done magically well at slowing or curing kidney disease in rodents but failed in clinical trials. So, the notion of channeling human stem cells to organize into a kidney-like structure is tremendously exciting because many of us feel that this potentially eliminates that 'lost in translation' aspect of going from a mouse to a human."

Kidney Donors

From Star2.com, BY REVATHI MURUGAPPAN

Age is no barrier to kidney donation if you are healthy

When Simah Empaling heard her child was gravely ill from kidney failure in 2012, she went on a hunger strike. She badly wanted to see her daughter, Ibi Uding, who was on dialysis.

Simah lives in Kampung Merakai, Serian, a village about 85km from Kuching, Sarawak, while Ibi was then in Kuching.

Alas, none of her other children were willing to take her to the hospital for fear that she might not be able to withstand the pain of seeing Ibi suffer.

So she refused to eat.

Eventually, Simah made the journey and broke down when she saw a pale Ibi in the ward, hooked up to a machine.

Ibi, 56, recalls: “She hugged me and cried, saying she could not allow her child to die before her. She kept asking what she could do to help.

“By then, I was constantly vomiting, urinating blood, giddy, couldn’t eat or drink, and had lost more than 15kg.”

Ibi had been diagnosed with polycystic kidney disease, an inherited disorder in which clusters of cysts develop primarily within the kidneys, causing them to enlarge and lose function over time.

“The symptoms started in 2007 with blood in the urine and a bloated stomach. If I carried heavy objects, I’d have back pain.

“I didn’t think much of it because I had three teenage kids and was busy running a business with my husband.

“I must admit that my diet wasn’t the best either,” says the former PKR Sarawak Wanita chief, who is saluted as the Iban torchbearer in her relentless fight for their rights.

As organ transplants involving non-relatives are not allowed in Malaysia and none of her other relatives were a compatible match, Ibi was in dire straits.

Then Simah offered to donate her kidney.

Initially, the doctors were hesitant as she was 79 then. However, Simah passed all the medical tests necessary for a kidney donor with flying colours.

“Prior to the transplant, my grandmother had never been admitted to hospital except when she delivered her six children.

“Her lifestyle is healthy as she used to plant padi and corn in the kampung.

“She also loves fishing, but we had to stop her because she cannot hear well anymore. We’re afraid she might not be able to hear the motorboats,” relates Ibi’s daughter, Seraphina Shantee, 26.

The adorable Simah chips in while Seraphina translates: “My late husband taught me how to fish, but now my children won’t let me go to the river.

“I used to be a strong rower, but I don’t have the same strength anymore.”

The only hitch was that Simah and Ibi were of different blood types.

Fortunately, consultant nephrologist Datuk Dr Tan Si Yen and his team were able to perform blood group incompatible, or ABOi, kidney transplants – the first in Malaysia to do so.

Thus, Simah became the oldest living kidney donor in South-East Asia.

Following the transplant, the doctors were amazed that Simah’s kidney functioned like it belonged to a 40-year-old.

She was out walking within three days of the operation, while it took Ibi a longer time to recover.

The first 100 days were crucial and Ibi adhered strictly to her doctor’s advice, although she contracted urinary tract infections twice.

It has been six years since the transplant was performed and the duo are doing well. They only have to go for check-ups annually.

Seraphina says: “My grandma has not fallen sick since. She needs assistance to walk and might complain from a bit of joint pain now and then, but that’s it.

“She doesn’t even have scars from the surgery. Her skin has healed so well.”

Simah, 84, lives alone in the village (her son lives next door) and continues to enjoy what life has to offer.

“From young, I eat only fish or chicken, and plenty of vegetables. I cook daily, mop and clean the house. I wake up at 8am and hand wash all my clothes,” she says.

Occasionally, Ibi, who now lives in Kuala Lumpur, will fly her mother over for a holiday.

“But she finds it boring here because we’re all at work. She will go knocking on people’s doors and make conversation with them.

“And because she can only speak Iban, the neighbours think she is a crazy woman and complain to the management!” says Ibi, laughing.

“One time we were in Kuching and I told her to stay downstairs while I went upstairs to take a shower.

“When I came down, I found the gates open, the air-conditioners and all lights switched on!

“She was sitting on the sofa and looking at me innocently. She has a curious nature and will turn on buttons to test what happens.”

Simah flashes me her warmest smile, oblivious to our discussion.

“Grandma is such a loving and caring person,” Seraphina adds.

Choking with emotion, a teary Ibi says: “I don’t know what I would have done without her. She’s proven that it’s never too late to donate a kidney. She’s been amazing… my saviour.”

Whole Foods Settles PKD Discrimination Suit; PKD and Dialysis: Is it effective? PKD Aortic Aneurysm Risk; Targeted Treatment for PKD Coming?

PKD And Your Health

From MD Linx

Outcome of autosomal dominant polycystic kidney disease patients on peritoneal dialysis: A national retrospective study based on two French registries

Researchers used data from two French registries—the French Renal Epidemiology and Information Network (REIN) and the French language Peritoneal Dialysis Registry (RDPLF)—to conduct two retrospective studies to assess outcomes in patients with autosomal dominant polycystic kidney disease (ADPKD) treated with peritoneal dialysis (PD). The investigators focused on survival and technique failure. Participants included patients who started dialysis between 2000 and 2010. According to findings, PD is a reasonable option for patients with ADPKD. In this study, only select patients with ADPKD were offered PD and there was no negative influence of PD on these patients’ overall survival. In addition, ADPKD status had no impact on PD technique failure.

From MD Linx

Risk of ascending aortic aneurysm in patients with autosomal dominant polycystic kidney disease

The paucity of data on aortic dilation in patients with autosomal dominant polycystic kidney disease (ADPKD) led researchers to compare sinuses of Valsalva (SoV) and tubular ascending aorta diameters in ADPKD patients with matched controls. Specifically, participants were 61 consecutive ADPKD patients who had an echocardiogram done. These patients were matched 1:1 with controls for sex, age, blood pressure and beta-blocker therapy use. The mean age of patients was 56±12 years. Among all the participants, 54% were men. Beta-blockers were received by 38%. Findings revealed that, ADPKD patients vs controls matched for common confounding factors for aortic dilation had an increased prevalence of aortic aneurysms

From BioWorld

Move over, cancer: Targeted therapy coming to kidney disease trial near you

Until recent years, polycystic kidney disease (PKD) was a renal indication in search of solutions – a situation even truer for its autosomal dominant (ADPKD) and autosomal recessive (ARPKD) subgroups. That dearth of drug development in the space is beginning to change, however, thanks to greater understanding of the genetic drivers of kidney disease and of the molecular pathways that are subsequently up-regulated and cause disease.Those findings are enabling researchers to apply precision medicine approaches that are the hallmark of targeted cancer therapies to indications such as PKD. Buy-in from regulators, who have shown willingness to explore creative alternatives to historically broad trial designs, are beginning to attract both big pharma and newer entrants to the opportunities in renal disease.

Living with PKD

From JD Supra

Whole Foods Market to Pay $65,000 To Settle EEOC Disability Suit

Employee Fired because of her Disability, Federal Agency Charged

RALEIGH, N.C. - Whole Foods Market Group, Inc., doing business as Whole Foods Market, headquartered in Austin, Texas, will pay $65,000 and provide other relief to settle a disability discrimination lawsuit brought by the U.S. Equal Employment Opportunity Commission (EEOC), the federal agency announced today. The EEOC had charged that Whole Foods Market violated federal law by failing to accommodate and firing an employee because of her disability.

According to the EEOC's lawsuit, Whole Foods hired Diane Butler in 2005 as a cashier for a facility in Raleigh, N.C. Butler has polycystic kidney disease, a genetic disease causing uncontrolled growth of cysts in the kidney, eventually leading to kidney failure. In 2009, while working for Whole Foods, Butler had a kidney transplant. The EEOC said that in December 2015, Butler missed work on two occasions because she had been hospitalized and needed to visit the doctor because of her kidney. The EEOC further alleged that although Butler informed Whole Foods that she needed time off due to her kidney impairment, the company nonetheless fired Butler because of her absences.

Such alleged conduct violates the Americans with Disabilities Act (ADA), which protects employees from discrimination based on a disability and requires employers to provide employees with disabilities with reasonable accommodations unless it would be an undue hardship. The EEOC filed suit in U.S. District Court for the Eastern District of North Carolina, Western Division (Equal Employment Opportunity Commission v. Whole Foods Market Group, Inc. d/b/a Whole Foods Market; Civil Action No 5:17-cv-00494-FL) after first attempting to reach a pre-litigation settlement through its conciliation process.

In addition to the $65,000 in damages, the two-year consent decree settling the suit requires that Whole Foods Market develop a disability accommodation policy. In addition, the company will provide annual training to its South Region human resource employees, and to managers and supervisors at its Wade Avenue store on the requirements of the ADA, including reasonable accommodation. Whole Foods Market must also post an employee notice concerning the lawsuit and employee rights under federal anti-discrimination laws.

"An employer who is on notice that an employee's absence is related to her disability must comply with the ADA's mandate to reasonably accommodate her by making exceptions to its absenteeism policy if doing so doesn't cause an undue hardship," said Lynette A. Barnes, regional attorney for the EEOC's Charlotte District. "Ignoring federal anti-discrimination law only makes things worse for a company as well as employees."

PKD Treatment: Need Equal Access; Use of Lanreotide NOT Supported

PKD Treatment

From McCleans, Canada, by PKD Foundation of Canada

Polycystic kidney disease: The need for equal access

For Canadians living with a surprisingly common genetic kidney disease, new research is bringing hope and, for the first time, the possibility of treatment, but serious access challenges remain.

In communities around Canada, people are living with polycystic kidney disease (PKD). The disease is common enough that you likely know someone suffering from it invisibly, and yet awareness of PKD remains low. With options now becoming possible for managing this incurable and potentially deadly disease, advocates are redoubling their efforts to raise awareness of not only the disease but the barriers preventing those who need treatment from equal access.

Jeff Robertson is the Executive Director of the PKD Foundation of Canada, the only national organization dedicated specifically to PKD awareness, research, and advocacy. And he wants you to know just how common and serious PKD really is. “PKD is a group of genetic diseases that cause fluid-filled cysts to grow on affected organs,” he explains. “It predominantly affects the kidneys, but it can impact other organs as well. Over time, in some cases these cysts can lead to organ failure. It’s a non-discriminatory disease, affecting men and women of all ages, races, and ethnicities. The prevalence is approximately 1 in 500 people globally. That amounts to roughly 66,000 Canadians.”

Access barriers

Many of those 66,000 Canadians have been waiting decades for progress in the fight against PKD. “Before, we had no options for slowing the progression of the disease,” says Dr. Andrew Steele, Nephrologist at Lakeridge Health. “Now, with new advances in medicine, we’re finally able to slow down that progression and possibly delay the need for dialysis or transplant. With newer agents coming to the market, hopefully in the future we can continue to push renal failure back even further.”

And yet, many Canadians with PKD are still unable to access these options because of a lack of private or public coverage. “Here we are at a day that many people didn’t think would come within their lifetime,” says Robertson. “Up until a few years ago, options for PKD patients were very limited. With that no longer being the case, the biggest challenge we now face is access. More therapies are currently in development, but without access, these will likely not be available for everyone with the disease.”

This is a disease where every day without intervention potentially worsens the prognosis for patients living with PKD. “The disease is progressive,” says Dr. Steele. “The cysts continue to grow and, with them, the total kidney volume. And we know that people with bigger kidneys are at more risk of progression through the stages of kidney disease.”

That’s why it’s so important that the playing field be levelled. And, because not every patient with PKD is currently a candidate for treatment, it’s equally important that we continue to promote research into new therapies that might help the underserved or improve things even further.

The first step is awareness

For a disease that affects so many, too few know about the struggle—not only the struggle of living with PKD, but the struggle for fair and equal access. As part of the effort to raise visibility, the PKD Foundation of Canada has been organizing Walk to END PKD events all over the country, providing those with the disease and those who support them with a chance to come out, be seen, and ask this country as a whole to stand with them in the fight for innovation, care, and access.

In the end, the message about PKD should be one of hope. Options are set to expand in the coming years. People are mobilizing. But, as Canadians, it’s essential that we ensure not one person living with this disease is left behind.

If you’re looking for additional resources, the PKD Foundation of Canada is solely dedicated to fighting PKD through research, education, advocacy, support and awareness. Please visit www.endpkd.ca to learn more.

From MD Linx, JAMA — Meijer E, et al. | October 29, 2018
Effect of lanreotide on kidney function in patients with autosomal dominant polycystic kidney disease: The DIPAK 1 randomized clinical trial

In patients with later-stage autosomal dominant polycystic kidney disease (ADPKD), researchers assessed the renal impacts of the somatostatin analogue lanreotide. The follow-up was performed for 2.5 years, during which no slowing of decline in kidney function was observed in association with treatment with lanreotide vs standard care. Overall, the use of lanreotide for treatment of later-stage ADPKD was not supported.

Methods
In this open-label randomized clinical trial with blinded end point assessment, researchers examined 309 patients with ADPKD from July 2012 to March 2015 at four nephrology outpatient clinics in the Netherlands.

Patients with 18 to 60 years of age and having an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2 were considered eligible.

Participants were followed-up till August 2017, meaning this trial ran for 2.5-year.

Either lanreotide (120 mg subcutaneously once every 4 weeks) in addition to standard care (n=153) or standard care only (target blood pressure <140/90 mm Hg; n=152) was randomly administered to patients.

Annual change in eGFR, evaluated as slope through eGFR values during the 2.5-year treatment phase was the primary outcome.

Change in eGFR before vs after treatment, incidence of worsening kidney function (start of dialysis or 30% decrease in eGFR), change in total kidney volume and change in quality of life (range: 1 [not bothered] to 5 [extremely bothered]) were all assessed as secondary outcomes.

Results
Randomization involved 309 patients (mean [SD] age, 48.4 [7.3] years; 53.4% women), of whom, 261 (85.6%) completed the trial.

According to findings, −3.53 vs −3.46 mL/min/1.73 m2per year (difference, −0.08; [95% CI, −0.71 to 0.56]; P=.81) was the estimated annual rate of eGFR decline for the lanreotide vs the control group.

In terms of incidence of worsening kidney function (hazard ratio, 0.87 [95% CI, 0.49 to 1.52]; P=.87), change in eGFR (−3.58 vs −3.45; difference, −0.13 mL/min/1.73 m2 per year [95% CI, −1.76 to 1.50]; P=.88), and change in quality of life (0.05 vs 0.07; difference, −0.03 units per year [95% CI, −0.13 to 0.08]; P=.67), no significant differences were observed.

The lanreotide group vs the control group demonstrated lower rate of growth in total kidney volume (4.15% vs 5.56%; difference, −1.33% per year [95% CI, −2.41% to −0.24%]; P=.02).

Injection site discomfort (32% vs 0.7%), injection site papule (5.9% vs 0%), loose stools (91% vs 6.6%), abdominal discomfort (79% vs 20%), and hepatic cyst infections (5.2% vs 0%) were documented as adverse events seen in the lanreotide vs control group.

PKD Clinical Trials: Metformin, Venglustat, Plan to Accelerate XRx-008

PKD Research

From BMC Nephrology

Metformin in autosomal dominant polycystic kidney disease: experimental hypothesis or clinical fact?

Background

Autosomal dominant polycystic kidney disease (ADPKD) accounts for 8–10% of end-stage chronic kidney disease (CKD) patients worldwide. In the last decade, the advanced knowledge in genetics and molecular pathobiology of ADPKD focused some aberrant molecular pathways involved in the pathogenesis of the disease leading to controlled clinical trials aimed to delay its progression with the use of mTOR inhibitors, somatostatin or tolvaptan. Preclinical studies suggests an effective role of metformin in ADPKD treatment by activating AMPK sensor. Clinical trials are currently recruiting participants to test the metformin use in ADPKD patients.

Methods

We retrospectively examined the records of our ADPKD patients, selecting 7 diabetic ADPKD patients under metformin treatment and 7 matched non-diabetic ADPKD controls, to test the effect of metformin on renal progression during a 3 year follow-up.

Results

During the first year, the GFR decreased by 2.5% in Metformin Group and by 16% in Controls; thereafter, renal function remained stable in Metformin Group and further decreased in Controls, reaching a 50% difference after 3 years of observation. Accordingly, the overall crude loss of GFR, estimated by a linear mixed model, resulted slower in the Metformin than in Control Group (− 0.9; 95% C.I.: -2.7 to 0.9 vs - 5.0; 95% C.I.: -6.8 to − 3.2 mL/min/1.73 m2 per year, p = 0.002).

Conclusions

Our data are suggestive of a beneficial effect of metformin on progression of ADPKD. Large, randomized, prospective trials are needed to confirm this hypothesis.

From PharmiWeb, Press Release

Research in Polycystic Kidney Disease Takes an Important Step Forward

Research in Polycystic Kidney Disease Takes an Important Step Forward Sanofi begins pivotal clinical trial to evaluate therapy for patients at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD)


BRIDGEWATER, N.J., Oct. 26, 2018 /PRNewswire/ -- Autosomal dominant polycystic kidney disease (ADPKD) is a devastating rare genetic kidney condition that leads to the growth of numerous cysts in the kidneys. Affecting an estimated 120,000 people in the U.S. and 170,000 in the European Union, ADPKD becomes so severe for approximately half of those patients that they face either a lifetime of dialysis or a kidney transplant.

Sanofi is beginning a pivotal clinical trial to study the safety, efficacy, and tolerability of an investigational oral agent called venglustat for certain patients with ADPKD. The international trial is enrolling patients who are at risk of rapidly progressive ADPKD.

"The initiation of this clinical trial is another reflection of Sanofi's commitment to research, advanced scientific discovery, and true innovation," said Gianluca Pirozzi, Head of Development for Rare Diseases and Head of Translational Gene Therapy, Sanofi Genzyme, the specialty care global business unit of Sanofi. "Our understanding thus far of both the cause and progression of ADPKD and the mechanism of action of venglustat present us with a path forward in this research effort."

Genetic mutation leads to devastating condition

ADPKD is caused by a mutation in the PKD1 or PKD2 gene that leads to a build-up of complex substances called glycosphingolipids in the kidneys. Glycosphingolipid accumulation is thought to be an important driver of cyst growth1,2. Relentless cyst growth can cause chronic pain and lead to reduced kidney function and kidney failure in ADPKD patients. The symptoms of ADPKD usually start to appear between the ages of 30 and 40, but they can begin as early as childhood for some patients.3

"The PKD Foundation welcomes research efforts that have the potential to bring new therapies to patients living with this condition," said David Baron, Ph.D., Chief Scientific Officer of the PKD Foundation. "We appreciate that Sanofi has engaged with the ADPKD patient community throughout the early stages of clinical development for venglustat and look forward to continuing to work with Sanofi."

About Venglustat

Venglustat is an investigational oral therapy designed to inhibit the abnormal accumulation of a substance in the body called glucosylceramide (GL-1), which plays a role in production of glycosphingolipids. In genetic mouse models of ADPKD, inhibition of glycosphingolipid production has been shown to reduce kidney cyst growth.4 The clinical significance of this is under investigation.

"Venglustat represents a potential opportunity for Sanofi Genzyme to expand its core legacy of expertise in lysosomal storage disorders and make an impact on patients living with other rare and challenging diseases," said Sébastien Martel, Global Head of Rare Diseases, Sanofi Genzyme. "Our progress related to evaluating venglustat in ADPKD once again highlights our company-wide commitment to continually build on our experience and focus our research efforts on unmet needs for patients around the world."

Venglustat has received Orphan Drug designation in the U.S. for the treatment of ADPKD. The ADPKD clinical trial will be conducted at sites in the U.S., Canada, China and Japan as well as several EU countries.

For more information on this trial, please visit https://www.clinicaltrials.gov or https://www.clinicaltrialsregister.eu. U.S. patients interested in learning more, may also visit https://adpkdtrial.org.

From Global News Wire, Press Release

XORTX Announces Revision to Polycystic Kidney Disease Clinical Development Plan

● Shorter Path to XRx-008 Marketing Approval ●

XORTX Therapeutics Inc. ("XORTX" or the “Company”) (CSE:XRX; OTCQB:XRTXF), a biopharmaceutical company focused on developing innovative therapies to treat progressive kidney disease (“PKD”), is pleased to announce that the Company’s clinical development plan has been reviewed and accelerated. This major revision to the Company’s original clinical development plan was acceptable to the US Food and Drug Administration (“FDA”) subsequent to XORTX’s submission of its pre-Investigational new drug (“IND”) information package and the Company’s in-person meeting held September 20, 2018 to discuss the comprehensive development plan.

Discussions with the FDA ranged across developmental topics including manufacturing, formulation, non-clinical study plans and clinical development strategy for XRx-008, including:
Review of XORTX’s proposed chemistry, manufacturing and formulation was confirmed by the FDA as acceptable with no material changes;

The proposed non-clinical development proposal was reviewed and confirmed the importance of characterizing the scale of increased bioavailability of XRx-008 in advance of clinical study initiation;

The proposed clinical development program for XRx-008, as a therapy for patients with PKD was outlined by the XORTX team and was composed of separate phase 2 and phase 3 clinical trials, followed by marketing application (NDA). Discussion and exploration with the FDA suggested a substantially shorter path to marketing approval for XRx-008 for ADPKD; and

The outcome of the pre-IND meeting is an accelerated clinical development plan composed of a study to characterize bioavailability XRx-008 in man, then a single, pivotal phase 2/3 clinical trial which would be eligible for special protocol assessment (SPA – see further information below).

Dr. Allen Davidoff, XORTX’s CEO stated, “We are very pleased with the positive meeting we had with the FDA that clarified that XORTX can simplify and accelerate its clinical study plan. The Company has now defined four clear steps to develop XRx-008 for autosomal dominant polycystic kidney disease patients (“ADPKD”): (i) manufacture clinical study ready drug for our upcoming clinical trials; (ii) file the IND and characterize the bioavailability and pharmacokinetics of XRx-008 in humans; (iii) complete the orphan drug designation (“ODD”) process for this program (see further information below); and, (iv) complete a pivotal phase 2/3 clinical trial. XORTX will seek a special protocol assessment (SPA) for this pivotal study. This accelerated clinical development plan substantially decreases the time and cost to bring this therapy to patients with PKD.”

Special Protocol Assessment (“SPA”) is one optional type of agreement submission that is available to sponsors, such as XORTX, for pivotal phase 3 trials. Through the SPA process, the sponsor and the FDA negotiate the design of a clinical trial that will support an efficacy claim for marketing approval. One advantage of the SPA is that, if an agreement is reached, XORTX would then have clarity in writing of the endpoints that must be achieved to support marketing approval.

Orphan Drug programs in the United States are programs for the treatment of rare disease which were passed into law in 1983 to facilitate development of orphan drugs – drugs for rare diseases such as ADPKD, Huntington’s disease, ALS and muscular dystrophy. These rare diseases typically have fewer than 200,000 patients living in the US and due to small patient numbers would not be considered economically feasible without government programs to support their economic viability. ODD does not indicate that the therapeutic is either safe and effective or legal to manufacture and market in the United States. That process is handled through other offices in the FDA, however an ODD designation would qualify XORTX for a number of benefits from the US federal government, such as reduced taxes and grants to fund future clinical trial work – a potentially substantial non-dilutive funding benefit to shareholders. Similar programs for rare diseases exist in European Union, Japan and other countries. Orphan drugs generally follow the same regulatory development path as any other pharmaceutical product, in which testing focuses on pharmacokinetics and pharmacodynamics, dosing, stability, safety and efficacy, however, some statistical burdens are lessened in an effort to maintain development momentum. As a result of world wide support for the development of therapeutic solutions to disease, orphan programs are some of the most successful, time and cost effective programs to develop.