PKD: Tolvaptan Study of Impact on Quality of Life

PKD Treatment

From healio.com

Tolvaptan showed no impact on QoL for patients with autosomal-dominant polycystic kidney disease

Treatment with tolvaptan did not appear to affect health-related quality of life for Swiss patients with autosomal-dominant polycystic kidney disease, according to study results.

“Recently, tolvaptan, an orally active, non-peptide selective arginine vasopressin V2R antagonist has been approved for the treatment of [autosomal-dominant polycystic kidney disease] ADPKD in many countries, including Switzerland,” Manuel A. Anderegg, MD, PhD, of Bern University Hospital in Switzerland, and colleagues wrote. “In two, randomized, double-blind, controlled phase 3 trials ... Tolvaptan lowered the increase in total kidney volume and kidney function decline compared to placebo.”

However, these benefits were coupled with a high frequency of aquaresis-related events including thirst, polydipsia, polyuria and nocturia, according to the researchers. Due to these adverse events, treatment guidelines have called for regular HRQoL assessment in patients treated with the drug. Researchers argued that despite these treatment recommendations, there remains knowledge gap on what impact, if any, tolvaptan has on HRQoL.

They initially included 121 patients from the Bern ADPKD registry, though the final analysis included 98 patients (treatment had to be discontinued in some of the study population due to aquaretic side effects or elevated liver enzymes; 30 patients with treatment, 68 patients without). All participants were asked to fill out the standardized kidney disease quality of life-short form (KDQoL-SF) questionnaire at the start of the study and after 1 year. The questionnaire assessed HRQoL with general measures (including physical functioning, role limitations caused by physical or emotional health problems, social functioning, bodily pain and vitality) and kidney-specific items (including effects of kidney disease, burden of kidney disease, work status, cognitive function, quality of social interaction, sexual function, sleep and patient satisfaction).

After adjusting for baseline scores, sex and age, researchers observed no difference between groups regarding general or kidney-specific HRQoL, except in patient satisfaction for which patients treated with tolvaptan rated as higher.

“The reasons for increased satisfaction in tolvaptan-treated patients can only be speculated,” they wrote. “Positive selection of patients that tolerated this novel disease-modifying drug in the analysis and close patient-physician relationship due to monthly visits for liver function tests are likely causes.”– by Melissa J. Webb

Portable Artificial Kidney Breakthrough Trials, Comparison of Dialysis Methods for Patient Survival

Dialysis 

From South China Morning Post, by Minghe Hu in Beijing and Coco Feng

Singaporean start-up’s portable ‘kidney’ could shrink dialysis machines, giving patients their freedom back

AWAK chief executive Suresha Venkataraya showcases the wearable artificial kidney in Beijing in December 2019. Photo: SCMP/ Coco Feng

For the past seven years, 70-year-old Singaporean Julia Lee has rarely travelled overseas. Her most recent trip was one night away, in neighbouring Malaysia.

Since being diagnosed with kidney disease, Lee has spent 10 hours each day hooked up to a 20-kilogram machine, making it difficult to move around.

Chronic renal disease results in a loss of kidney function, meaning the patient’s body is unable to clear the blood of waste and excess fluids. Dialysis – the treatment Lee goes through which involves machines removing excess water and toxins from the patient’s blood – is the only option for those whose kidneys are no longer able to perform their function, save for a kidney transplant. Some like Lee, whose heart problems make her unsuitable for a transplant, have to rely on the treatment permanently.

“If there was a portable device that could be carried around and used at home, it would be more convenient for me,” Lee said. “Maybe I would be able to travel more.”

But a Singaporean company is offering new hope with its work on a portable artificial kidney weighing just 2 to 3 kilograms, as advances in technology begin to drive more human and machine interaction in health care.

Founded in 2007, AWAK Technologies is among a group of start-ups worldwide – including Sweden's Triomed, US firm Wearable Artificial Organs and Dutch start-up Nanodialys – that are looking into ways to make wearable dialysis machines.

AWAK is the only one from Asia, and it has made some headway in gaining recognition from both regulators and investors.

A year ago, its portable artificial kidney was granted “Breakthrough Device Designation” by the US Food and Drug Administration (FDA), a qualification that could expedite the development and review of certain medical products.

The start-up also recently raised US$40 million in a series A1 fundraising round co-led by Vickers Ventures Partners and an unnamed global medical product company. Other investors include medical technology manufacturer Advanced MedTech and the investment arm of government agency Enterprise Singapore, SEEDS Capital.

The artificial kidney, worn externally, consists of a permanent pump and a disposable cartridge that acts as an advanced filter to clear toxins from the body.

Like the machine Lee uses, AWAK’s device carries out peritoneal dialysis (PD), one of two main types of dialysis. PD involves a solution being injected into the abdominal cavity to absorb waste products and toxins before being removed. The other main type of dialysis, haemodialysis (HD), involves extracting the patient’s blood, cleaning it and returning it to the body.

Despite its smaller size compared to regular PD machines, AWAK's device can be used for seven to 10 hours a day. It only holds 250 millimetres of fluid but the cartridge can clean the toxin-laden fluid after it is extracted from the patient's body and push it back repeatedly, processing about two litres of the solution each hour.

Although the company said it has not studied the efficiency of this system compared to conventional PD devices yet, the one Lee uses processes half a litre of solution per hour and has to hold a larger amount of fluid as it cannot be reused.

There is a large potential market for AWAK’s product: about 2.6 million people worldwide underwent dialysis in 2010, and the population is projected to double by 2030, according to a 2015 Lancet study.

To be sure, the new device still has some limitations. Although AWAK enables patients to work, attend school and go shopping more easily than before, possible contamination from the environment remains a concern.

As with conventional PD treatment, patients will need to find a clean place to reduce the risk of contamination, according to Sydney Tang, a professor of renal medicine at the University of Hong Kong.

However, as there are no more connections between the patient’s body to the device than conventional PD, “the risk of contamination should not be higher” theoretically, he said.

According to AWAK chief executive Suresha Venkataraya, the device tested safe in the most recent clinical trial in 2018, although this was conducted in a controlled environment in the Singapore General Hospital and patients were not allowed to leave the centre.

The company hopes to conduct further trials in about 12-18 months with the aim of getting government approval in Singapore, Venkataraya said, adding that one of its biggest challenges was recruiting patients for the trials.

If its upcoming trials are successful, AWAK could be the first to successfully launch a portable PD machine of this kind. But several of its competitors may also be close: a spokesman from Nanodialysis said that the company expects to launch its wearable PD device in 2022, first in Europe and then in Asian countries like Japan and China as well as the US, while Triomed completed a trial of wearable PD devices with five patients in 2018.

Lee said she would be excited about a portable dialysis device but price is a concern. The monthly cost of her current treatment, including machine rental and the dialysis fluid, is S$2,000 (US$1,480). This is mostly covered by national health care programmes as well as subsidies from the non-profit Kidney Dialysis Foundation, she said.

The price of the AWAK device has not been determined, although Venkataraya said the company wants to make sure that the cost can be covered by medical insurance in each market.

After launching in Singapore, AWAK hopes to introduce the device in Hong Kong, Australia, Europe and the US, Venkataraya said, adding that Singapore and the European regulators generally approve products faster than the US FDA. AWAK still does not have a clear timeline for the US market, where it can take an average of three to seven years for a medical device to clear regulatory scrutiny and launch.

On the company’s choice of its first market, Venkataraya said that while Singapore is not big, it does have high population density “where in one or two hospitals, you can find many patients and a lot of support”.

Government support was also a factor: “The National Medical Research Council gave us a grant for the trial and Enterprise Singapore also gave us early grants and funding which we really needed. So the whole ecosystem was very supportive,” he added.

From Eureka Press, UNIVERSITY OF LIMERICK

UL study reveals 'identical' survival for kidney dialysis patients using different treatments

Research carried out at University of Limerick has shown that life expectancy outcomes for two of the most common forms of kidney dialysis treatment are "virtually identical".

In the largest study of its kind, researchers from the Graduate Entry Medical School (GEMS) at UL compared the survival of patients with kidney failure that were treated with either peritoneal dialysis (PD) or haemodialysis (HD) at a dialysis centre, two of the most common forms of available treatments.

The researchers found that the survival of new patients with kidney failure was similar irrespective of treatment type - PD or in-centre HD - and have recommended that this new knowledge be incorporated into policy documents to enable patients and their providers make the best decisions on optimal treatments.

Prior to the study, questions had been raised by the scientific community as to whether one form of dialysis was superior to another in terms of survival benefit. This answer to this question is of "huge significance" according to Professor Austin Stack, Foundation Chair of Medicine and Lead Investigator for the Kidney Research Consortium at UL.

"There has been huge debate on this issue, as they are very different treatments for kidney failure," said Professor Stack.

"Defining whether one treatment confers a survival advantage over another for patients who develop kidney failure is of utmost importance. We have shown in this study that the life expectancy was virtually identical on either of these therapies. This is hugely important as it means that patients have a choice," he added.

The systematic review, a pooled meta-analysis of 17 cohort studies with over 113,000 dialysis patients between 1993 to 2014, was conducted by the research team at UL in association with the Departments of Nephrology and Internal Medicine at University Hospital Limerick, and the findings have just been published in the international journal Nephrology, Dialysis and Transplantation.

"Prior studies on this topic have yielded conflicting results," according to Dr Mohamed Elsayed, the primary author of the study, Research Fellow and Specialist Registrar in Nephrology.

"Indeed, when we looked at the available international literature, we found that the results tended to vary by country, and according to the year the study was carried out. One potential reason for this is that patients who are selected for PD differ from those who are selected for HD, and that practice patterns tend to vary across countries.

"The ideal method for comparing the survival of these two treatments would be a randomised controlled clinical trial but unfortunately due to logistical challenges and recruitment difficulties investigators have failed in the past to successfully complete such trials.

"The next best method is to use an approach that carefully considers the differences between PD and HD and conduct comparisons using what is called a propensity-score matched approach. Such a comparison allows us compare the treatments take into account baseline differences between the patient groups," he added.

The study pooled together the results from research that used a propensity-based approach and found that patients who began dialysis either with in-centre HD or PD experienced similar survival (Hazard Ratio 1.06, 95% Confidence interval 0.99 to 1.14). The findings were remarkably similar for patients with and without diabetes and were consistent across studies that included European, North American and Asian Cohorts.

Despite the overall similar survival between PD and HD, it did uncover important differences from country to country and across different time periods. Importantly, it also found that the survival of PD was better than that of HD in more recent time periods (after 2007).

These research findings have important implications, according to Professor Stack, on how we manage patients with imminent kidney failure approaching dialysis.

"All else being equal, both of these therapies are effective at extending patient survival, and thus the conversation with patients should revolve around which of these treatments is the most suitable treatment from a lifestyle and quality of life perspective," he explained.

"Globally, the rates of use of PD are substantially lower than those of HD, with less than 10% of dialysis patients receiving PD as a maintenance treatment. In the United States, around 10% of dialysis patients are receiving PD with the majority treated with HD. Similarly, in Ireland, the rates of PD use are remarkably low, with only 9.5% of patients utilising PD leaving room for improvement.

"Peritoneal dialysis is a form of dialysis that be provided in one's home, and lead to better quality of life and greater independence. Economically, PD is the cheaper form of therapy compared to in-centre HD with costs that are on average €20,000 lower.

"Given that PD has at least similar survival to HD, and the fact that PD is more cost effective, and leads to better preservation of lifestyle, we advocate that PD should be encouraged as a first-line therapy for many patients with approaching kidney failure," he added.

ADPKD Patients Needed for Study, New Kidney Donation Rules, Perfect Match, Medicare Drug Policy Creates Transplant Problem

Kidney Donation

From PKD Foundation, Blog, by Alexis Denny, Director of Government Affairs
Understanding new rules and regulations around kidney donation — Part One

In 2019, the U.S. Department of Health and Human Services (HHS) took major steps to increase the availability of organs for the 113,000 Americans on waitlists for lifesaving organ transplants — 20 of whom die each day. In the July Executive Order (EO) from President Trump, the Centers for Medicare & Medicaid Services (CMS) proposed changes in organ procurement and organizational accountability.

On December 18, 2019, Alex Azar, Secretary of Health and Human Services (HHS), announced new rules designed to alleviate some issues felt by the kidney community:
A Health Resources and Services Administration (HRSA) proposal to remove financial barriers to organ donation, specifically through adjustments to how the National Living Donor Assistance Center (NLDAC) administers reimbursements to living donors.
Changes to the way organ procurement organizations (OPOs) are held accountable for their performance by increasing regulation and oversight.

Proposed changes

Back in July, the EO promised change in three places: (1) prevention and dialysis; (2) transplant and living donation; (3) innovation and treatment. The new rules laid out in December will address number two from the EO — transplant and living donation.

These new rules are part of a larger effort by the kidney advocacy community to work with the Trump Administration to increase visibility, resources, and support for chronic kidney disease and kidney transplantation. The work over the past years to engage the President, Secretary Azar, and others and the receptivity we’ve received has been a long time coming. These new rules are concrete results of this effort.

From Calgary Sun, Canada

Man donates kidney to wife of 51 years after finding out he's a perfect match

Mike and Peggy Nipper. (St. David’s North Austin Medical Center photo)

If being married for half a decade isn’t enough to prove your love, maybe donating a kidney to your spouse will do it.

When Peggy Nipper’s diseased kidney began failing — she has polycystic kidney disease (PKD), a genetic condition that causes cysts to develop in the kidneys — and dropped to 14% functionality, requiring a transplant or dialysis, her husband of 51 years, Mike, was tested to see if there was a remote possibility he matched her, according to CNN.

Turns out, Mike Nipper was a perfect match for his 74-year-old wife, a shocking turn in a process that generally takes seven years to find a compatible donor.

The couple underwent the transplant in November at the Kidney Transplant Center at St. David’s North Austin Medical Center in Texas.

“It was quite a gift,” Peggy told CNN. “I don’t think he has to give me another gift for the rest of my life. This was the ultimate present.”

From Stat, By MATTHEW COOPER, M.D.

Medicare policy on antirejection drugs imperils kidney transplants

For people with failing kidneys — and there are thousands of them in the United States — a kidney transplant offers a new lease on life. But like every other type of transplant, its success depends on taking drugs for life to suppress the immune system. Otherwise, the body begins rejecting the transplanted organ.

That’s basic medical science. So it makes no sense that Medicare covers these drugs for just 36 months for the majority of people who receive new kidneys. Because of this, many patients find themselves back where they started in a risky and frightening place: on dialysis and in need of a new kidney that for many will never come.

Chronic kidney disease (CKD) is the ninth leading cause of death in the United States, claiming more lives than breast cancer or prostate cancer. More than 37 million Americans are living with CKD today. Individuals with irreversible kidney failure, known as end-stage renal disease, have only two choices to survive: undergo regular and frequent dialysis or be fortunate enough to receive a kidney transplant.

Since 1973, Medicare has covered the care for individuals with irreversible kidney failure, or end-stage renal disease. Dialysis does mechanically what the kidneys do naturally: removes waste products and excess fluid from the body. Most people undergo dialysis at a hospital or dialysis center, usually three times a week for about four hours each time. Medicare spends $86,300 a year per patient on dialysis, and there is no time limit on this coverage.

Kidney transplantation is a medical success story. It can dramatically improve the recipient’s quality and length of life. But not everyone who needs a donated organ receives one. There are currently more than 103,000 individuals on the kidney transplant waiting list, while just 23,000 kidney transplants were performed in 2019.

The upfront cost of a kidney transplant is about $110,000. Afterward, coverage of immunotherapy under Medicare Part B is approximately $2,300 per year. The savings to the government of providing immunosuppressive medications are clear.

As Medicare law currently stands, patients’ lives are at risk, donor kidneys are being neglected, and taxpayer money is being squandered. It’s time for change. That’s why I’m testifying before Congress Wednesday in support of lifetime Medicare coverage of immunosuppressive medications for kidney transplant recipients.

As a transplant surgeon for nearly 20 years, I have witnessed firsthand the impact of this shortsighted policy. Patients struggle to pay for the immunosuppressive drugs needed to maintain their transplants when their Medicare coverage ends, especially lower-income patients who lack group health insurance or who do not qualify for Medicaid or other assistance. These financial pressures force some patient into rationing their immunosuppressive drugs or forgoing them altogether, either of which generally results in the failure of the transplanted kidney.

I can recall several patients who had to choose between paying their mortgage or utility bills and paying for their transplant-saving medication. Many of my colleagues report that they encounter patients in similar situations. A 2012 New England Journal of Medicine article reported that nearly 70% of kidney transplant programs reported either a death or transplant loss due to patients’ inability to pay for their antirejection medications.

The 36-month limitation on coverage also has a detrimental effect on living kidney donations. Patients are reluctant to ask a friend or family member to be a living donor if they fear they will be unable to afford their antirejection medications long term. As an advocate for increasing kidney donation, I have trouble asking living donors or donor families to give the most amazing “gift of life” knowing that Medicare will cut off necessary immunosuppressive coverage after three years.

In May of 2019, the Department of Health and Human Services conducted an analysis that indicated potentially significant cost savings from extending immunosuppressive coverage for kidney transplant patients by averting future dialysis and re-transplantation. The Centers for Medicare and Medicare’s Office of the Actuary concluded that extending coverage could save Medicare up to $300 million over ten years.

In December 2019, Reps. Ron Kind (D-Wis.) and Michael Burgess (D-Texas) introduced the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act (H.R. 5534). This legislation would extend Medicare coverage of immunosuppressive medications for kidney transplant recipients for life.

By providing this coverage of last resort, Congress can help reduce the likelihood of the failure of transplanted kidneys, minimize the need for repeat transplants, enable more patients to pursue transplants, and save taxpayers money on the potential cost of re-transplantation. Most importantly, this measure also honors the gift of kidney donation for those who gave selflessly so others may have a second chance at life.

The current 36-month coverage policy for immunosuppressive drugs is not medically, economically, or ethically justified. Congress must fix it.

Matthew Cooper, M.D., is the director of kidney and pancreas transplantation at Medstar Georgetown Transplant Institute, professor of surgery at Georgetown University School of Medicine, and a board member of the National Kidney Foundation. He reports receiving consulting and research fees from several companies that manufacture immunosuppressive drugs. More information about H.R. 5534 is available at Honor the Gift, a patient-centered campaign for extending Medicare coverage of kidney transplant antirejection medications sponsored by CareDx, a precision medicine company focused on improving transplant outcomes.

PKD Research

From PKD Foundation

ADPKD Patients Needed for a New Research Study

We’re looking for patients who meet the following: 

• Males and females between the ages of 18 to 50
• Have been diagnosed with ADPKD
• Kidney function between 45 to 90 mL/min/1.73m2 eGFR
• Not currently taking Tolvaptan

Other eligibility criteria will apply.

Participation in STAGED-PKD is divided into two separate stages, each lasting up to 26 months and will include taking an oral study medication daily. The investigational drug, study-related procedures, and doctor visits will be provided at no cost.

Link to More Information about this study.

Clinical Studies webpage link at PKD Foundation.

Take part in clinical research!


Local doctors are currently conducting a Phase 3 trial of an investigational oral therapy for individuals at risk of rapidly progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD); the purpose of the trial is to determine if GZ/SAR402671, an investigational medication, is as safe and effective as a possible treatment for ADPKD.


ABOUT THIS STUDY The Phase 3 trial, known as the STAGED-PKD study, will be run in 2 parts and aims to enroll 640 people across approximately 80 international sites located in the Americas, Europe and Asia-Pacific. The company expects to complete the trial by 2023. The study is divided into 2 separate stages. Each stage will consist of a 30-day screening period, a 2-week period where placebo is taken, a 24-month study treatment period, and a 4-week post-study treatment follow up period. The total length of participation and treatment in the study will be the same in Stage 1 and Stage 2 (up to 26 months participation for each stage). Stage 1 of the study enrollment is currently ongoing. Participants are randomly assigned to 1 of 3 study groups and will take the oral study medication GZ/SAR402671 (8mg or 15mg), or matching placebo, once daily over the duration of approximately 24 months. After Stage 1 of the study finishes, Stage 2 will start. Patients in Stage 2 will receive either placebo or GZ/SAR402671at the highest dose determined in Part 1 to be safe and effective.