PKD, Understanding Types of Kidney Cysts, Gift of Life from: Navy Seal; Runner to Coach

Kidney Cysts

From Times Life Style, by Paul Becker

What Are Kidney Cysts? Kidney Cysts Symptoms, Causes, and Treatments

Kidney cysts are one of the many factors that affect the kidney health. A cyst is a small fluid-filled sac which forms inside the kidneys. Kidneys are responsible for filtering out the wastes from the bloodstream and dispose it out from the body in the form of urine. An individual can suffer from both single cyst and multiple cysts.

The human kidneys are affected by two types of cysts – simple cysts and polycystic kidney disease. A simple cyst is formed of thin walls and is usually an individual cyst filled with a water-like fluid. A simple cyst doesn’t harm the kidney health nor does it affect its functioning.

Polycystic Kidney Disease (PKD), on the other hand, is an inherited condition in which the patient suffers from multiple cysts inside his/her kidneys. PKD can harm the kidneys in a bad way. The more it grows the more harm it does.

However, the cysts don’t cause any symptoms and are usually harmless. An individual may not even realize that he/she has cysts in his/her kidneys until he/she has undergone a test for some reason.

The size of a kidney cyst and what does it mean

In normal cases, the cysts are too small to be seen with the naked eye. The doctors use microscope to examine such cysts. However, in case of PKD, the cysts can sometimes grow as large as a tennis ball. Larger cysts pose as a threat to other organs as they can press against the nearby organs causing severe pain.

Kidney Cyst Symptoms

Simple cysts are known for not causing any symptoms but in case of PKD, when the cysts grow larger and become infectious; it can cause the following symptoms.

For Simple Cyst 
Dark urine
Blood in the urine
Uncontrollable bladder
Swelling of the abdomen
Upper abdomen pain
Back pain, upper body pain, pain in the side between the pelvis and ribs. Happens when the cyst tends to pop or burst.
Fever

For Polycystic Kidney Disease (PKD) 
Blood in the urine
Upper body pain, pain in the sides and back
High blood pressure

Kidney cysts causes and risk factors

The mystery behind how simple cysts are formed is still a mystery. The doctors don’t know the exact reason why simple cysts are formed, but they do have few possible explanations.

A human kidney is composed of millions of tiny tubules that collect the urine. The theory says that when these tubules get blocked due to some reason or swell up or fill with liquid, cysts may start to grow.

Another theory suggests that when small pouches known as diverticula filled with liquid starts forming in the weakened areas of the tubules, it may trigger the cyst formation.

Cysts are likely to affect an individual when he/she gets older. 40 years is the cyst triggering age. By the age 40, 25% of the people are likely to get affected by the simple cyst. However, men are more prone to developing cysts in their kidneys as compared to women.

Polycystic Kidney Disease (PKD), on the other hand, is caused mostly because of the inheritance. Those with a family history of cysts are more likely to get affected.

Cyst Complications

Cysts are not that complicated but sometimes it can lead to;
High blood pressure
Burst cyst
Infection in the cyst
Blockage of urine
PKD, on the other hand, can easily damage the kidney health with time.

Cyst Treatment

Urologists are the one who deals with patients suffering from kidney complications. The urologist will take the urine and blood sample of the patient to see how his/her kidneys are functioning.

For diagnosing cysts, the urologist will perform the following tests:
Computer Tomography (CT) Scan
Magnetic Resonance Imaging (MRI) Scan
Ultrasound

Simple cysts can be easily cured by consuming probiotic kidney health supplement and other healthy foods. Also, there are several medications for cysts prescribed by the doctors.

In case of PKD, the treatment includes:

Surgery – cysts are removed laparoscopically by making small multiple incisions.

Sclerotherapy – in sclerotherapy, the doctor drains out the cyst. The doctor uses an ultrasound for navigation and the patient is given simple anesthesia as it can be a painful affair.

Gift of Life

From People

Stranger Provides Transplant For a Desperate Mother of 3: 'I Love Her Just Like She Was Family'

Though he didn’t know her, a former Navy SEAL came to a mother’s rescue just as pressure was mounting to find her a life-saving organ donor.

As 35-year-old Melinda Ray’s health deteriorated due to a polycystic kidney disease that spread to her liver, she and her husband, James Ray, were desperate to find a transplant. The condition caused continually spreading cysts to develop on Melinda’s liver, which led to it growing larger in size and placing stress on the rest of the organs in the increasingly cramped space.

The couple, who have three children and live in Colorado, came up empty-handed in their search for donor candidates, and as Melinda’s strength weakened, she turned to Facebook in September that detailed her emotional ordeal and offered a last-ditch call for help.

That Facebook message reached Robin Ihnfeldt, a best friend of Melinda’s sister, who texted the story to her husband, Jeff Bramstedt. The former 13-year Navy SEAL veteran instantly felt compelled to help the woman he had never met.

“When my wife told me about it, it just wasn’t okay with me that somebody was going to die,” Bramstedt, 47, of San Diego, California, tells PEOPLE. “It took me literally two seconds to make a decision and I just said, ‘I’ll do it, let’s go.’ ”

With Bramstedt on board, he and his wife both signed up to go through the screening process to find out if they were matches. Though his wife didn’t qualify because doctors discovered her blood clotted too quickly to undergo the surgery, Bramstedt continued on with the screening process, answering questions about his social history and taking blood samples, until doctors flew him out for more intensive tests. Then, around Thanksgiving, he returned to UCHealth University of Colorado Hospital for the pre-op, where he met Melinda and James for the first time.

“As soon as I saw her, I was just instantly connected to her. They’re just such amazing people,” Bramstedt recalls. “We just talked for about an hour, and just got to learn about each other’s families, and we knew right away we were going to be connected for life.”

After doctors solidified Bramstedt as a match, he agreed to undergo a 10-hour-long surgery to give Melinda 30 percent of his liver that would eventually regenerate. Doctors explained he would be placing himself at great risk by undergoing the operation, but not one to let danger get in the way of things, Bramstedt—a movie stuntman and a skydiving instructor at Skydive San Diego—was set on going through with it.

On Dec. 4, the pair underwent successful surgeries, led by Dr. Elizabeth Pomfret. Bramstedt then spent two days recovering in the ICU, and once he was released, he and his wife stayed with a friend in Denver as he recuperated.

“My wife monitored my meds, and took care of me,” he says. “I don’t listen to doctor’s orders very well, so she was definitely the doctor’s lieutenant on that—very strict!”

Going on three weeks after the operation, Bramstedt says he is running on about a “three-hour battery” and is sleeping much of the day. But things are getting better, and he keeps in contact with Melinda and James often.

“I never had a little sister before, and now I do,” Bramstedt says. “I love her just like she was family, like she was a blood relative. In essence, she kind of is, we share DNA at this point. She’s stoked on life, and I’m excited for her.”

He says the experience changed the way he views the world, and he hopes other healthy people are inspired to become organ donors and support services such as those provided by UCHealth.

“If you have health and are strong, and if you are young and have all this energy and love to be active, maybe you are a prime candidate for somebody and can affect their lives in a positive way,” he says. “An average guy can step up and be a hero to somebody whose life is going to end. Hopefully, we can make my and Melinda’s story not so extraordinary.”

From Chicago Tribune, by Donna Vickroy

'An amazing sacrifice': Runner to donate kidney to Homewood coach

It's hard to top the gift Rich Matula soon will be receiving from his friend, Mike Blake.

"It's humbling," Matula said. "It's an amazing sacrifice."

On Jan. 9, Blake, an accountant from New Lenox, will donate a kidney to Matula, a marketing manager from Homewood.

The donation will not only enable Matula, who was born with polycystic kidney disease, to avoid having to go on dialysis, it should enable him to continue his lifelong pursuit of running.


Maybe, Matula joked, he might even be able to "beat Mike in a race."

Matula, who is married and has a 5-year-old son and 20-year-old stepdaughter, has been coach for the Tinley Track and Trail running club for 15 years.

The group is made up of 50 men and women from the south suburbs and Northwest Indiana, committed to improving their times. They practice in Tinley Park, Orland Park and Palos Heights, and compete in events, from 5Ks to the Boston and New York City marathons.

Blake is a longtime member. He is known for his speed, and he acted fast last year when he learned the severity of Matula's condition.


"I had called him for some running advice," Blake said.

During the conversation, Blake asked Matula about his kidney function. When he learned it had dropped to 16 percent and that his beloved coach was on the waiting list for a transplant, he offered to get tested.

That initial testing took place exactly one year before the transplant surgery is set to occur.

As extraordinary as his gift is, Blake said any member of the club would have offered to donate a kidney to Matula if he hadn't beaten them to it.

"Rich is so loved by this group," Blake said. "Anyone would do this for him. I just happened to be the one who got tested first."

Dr. Yolanda Becker, surgeon and director of the kidney and pancreas program at the University of Chicago, where the transplant surgery is scheduled to take place, said, "This is the ultimate Christmas gift; it is truly the gift of life."

The transplant, she said, "is going to change Rich's life, in terms of how he feels."

She said Matula, who is system director for customer relationship management at Presence Health, helped himself as much as he could by staying healthy and staying fit, even as his kidney function declined, and his energy level waned.

"He has done all the right things to keep himself as healthy as possible for as long as possible," Becker said.

But, she added, he also is lucky to have a donor who is not only a close friend, but one who is also in great shape.

According to the United Network for Organ Sharing (unos.org/), there are 103,000 patients on the kidney transplant waiting list.

"In a typical year, only about 16,000 transplants will take place, and of those, just over 5,000 are from living donors," Becker said. "So there's a huge inequity, and people die on the waiting list."

The surgery will leave both men with one healthy, efficient kidney and that, Becker said, is all a healthy human needs to live a "normal lifespan and a normal lifestyle."

The recipient's insurance pays for the donor's workup, she said, and should something befall the donor's kidney function in the future, he would be moved to the top of the donor waiting list.

Becker said as "wonderful" as it is for the recipient, organ donation is also an opportunity for the donor to change someone's life.

That sentiment was something close to Blake's heart. He said in addition to wanting to help his friend, he embraced the chance to impact another human being.

"My wife did in-home day care for years. She affected a lot of people's lives. These (grown) kids still come and visit her. I've always been a little envious of her ability to impact others," Blake said.

"I'm an accountant. In my job I don't affect anyone's life in a positive way. I know I affect my children's lives and my wife's life, but it feels good to affect someone else's life," he said.

Blake and Matula are 53, in the same age group for competing.

"When I was healthier," Matula said, "we'd compete against each other. Mike probably beat me 80 percent of the time."

He's hoping the new kidney will bring some new bragging rights, as well.

"That's the real reason I'm giving it to him," Blake joked. "I got tired of his kidney excuse. So now when I beat him, it'll be even more awesome because he'll have three kidneys to my one."

On a serious note, Blake said he doesn't expect the surgery to affect his running ability, but if it does, "it still will have been well worth it.

"If I was in my prime," he said, "it might matter. But I'd still do this for him."

Club member Donnie Smith, who lives in St. John, Ind., said the whole team is pulling for the man who has been a support and an inspiration to each of them over the years.

"Rich cares. He sees everything. He pushes us to be our best," said Smith, a 44-year-old commodities broker.

There's a deep admiration, Smith said, "for people who inspire you to do your best work.

"Rich is a natural coach," he said.

For the team to be able to turn the tables and encourage him through the surgery is only fitting, he said.

When Rudy Cvetkovich, of Homer Glen, joined the group eight years ago, "I was kind of slow."

Matula and the other runners, he said, "pushed me to reach my potential."

This past year, Cvetkovich, 51, qualified for the Boston Marathon.

"These guys are my best friends," Matula said. "We race together, we train together. Through the blood, sweat and tears, you form a brotherhood."

On the day of transplant, Blake's surgery is expected to start two hours before Matula's.

"As soon as my kidney comes out, he'll be ready to receive it," Blake said.

"We've been told we could end up in rooms next to each other," he added.

If so, the two will be able to rib each other during recovery.

"Mike has the worst sense of direction," Matula said. "So, we're kind of worried that might pass over with his kidney."

dvickroy@tribpub.com

PKD Foundation Washington Summery

PKD Politics

From PKD Foundation

Washington Summary December 2017

Tax Reform and Health Care

The details of the final tax bill (HR 1) were released on Dec. 15. Here are the provisions impacting health-related issues.

Deduction of medical expenses: The final bill states that for two years (2017 and 2018 tax years), taxpayers will be able to deduct medical expenses above 7.5 percent of their income. In 2019, the bill returns to the current status – permitted medical deduction to expenses above 10 percent of income.

Orphan Drug Tax Credit: The final bill cuts the tax credit in half; in the future it will be 25 percent of eligible expenses. The PKD Foundation and many other patient advocacy groups supported retaining this vital tax credit. Although we are pleased that the credit was not eliminated, we are disappointed that it is being reduced.

ACA individual mandate: The final version contains the Senate language that repeals the individual mandate.

Tuition for graduate students: The bill keeps the present tuition exemption for certain graduate students. This is particularly important for biomedical grad students who also are conducting research on rare diseases such as PKD.

Each household’s tax situation is unique. The impact of the new tax bill will depend on income, family situation, residence, and other factors. For more details on the final version of HR 1, visit the Ways and Means Committee website at house.gov and the Finance Committee website at senate.gov.

Congress continues to discuss ways to stabilize the ACA individual insurance market by providing cost-sharing reduction (CSR) funds. More than 200 groups have endorsed the proposal drafted by Sens. Lamar Alexander (R-TN) and Patty Murray (D-WA). Sens. Susan Collins (R-ME) and Bill Nelson (D-FL) have their own proposals to stabilize the individual insurance market through direct funding and a reinsurance program similar to previous state-based risk pools. Whether any of the efforts will be included in the next spending package (the continuing resolution or CR) remains to be seen.

Fiscal Year 2018 NIH Funding

In September, the House passed a bill that increases funds for NIH by $1.1 billion over the FY17 funding level. The Senate Appropriations Committee approved a proposal to increase NIH funding by $2 billion in FY18.

The current continuing resolution (CR), which is funding NIH at last year’s level, expires on Dec. 22. If Congress does not pass another CR, most government agencies (including NIH and FDA) will close operations temporarily.

There still is time for advocates to contact Congress with a simple message: accept the $2 billion Senate funding level increase for NIH for the rest of FY18.

Essential Health Benefits

In early November, CMS issued proposed rules that would make it easier for states to define “essential health benefits (EHB)” for health insurance coverage. Interested groups (such as insurers, hospitals, providers, and regulators) raised numerous questions about the changes. Some even stated that allowing states to change EHB would return the insurance market place to its pre-ACA situation when pre-existing conditions prevented people from purchasing affordable and comprehensive insurance to cover their medical needs.

CMS is reviewing the public comments on the proposal and will issue final regulations in the near future.

Medicare and Chronic Kidney Issue

The bipartisan Care Demonstration Program for Chronic Kidney Diseases bill (HR 3867) would establish a pilot program to encourage health practitioners to identify early systems of CKD. The goal is to lower overall health care costs by providing better treatment for CKD patients. Reps. Markwayne Mullin (R-OK), George Holding (R-NC), GK Butterfield (D-NC), and Linda Sanchez (D-CA) introduced the bill.

Veterans and Organ Transplants

In November, the House passed HR 1133, the Veterans Transplant Coverage Act. The bill would allow an eligible veteran to receive an organ transplant from a non-veteran at any convenient medical facility, whether a VA hospital or not.

Sen. Dean Heller (R-NV) introduced a similar bill in the Senate (S 115). Sen. John Cornyn (R-TX), the Majority Whip, is a cosponsor.

Bills of Importance to the PKD Community

Living Donor Protection Act (HR 1270/no Senate bill yet) would remove barriers to living organ donation. Rep. Jerrold Nadler (D-NY) and Rep. Jaime Herrera Beutler (R-WA) introduced the bill. PKD and several other patient groups have signed a letter urging House Members to cosponsor HR 1270.

The OPEN Act (HR 1223/ S 1509) would make it easier for companies to repurpose approved drugs for treating rare diseases. Reps. Gus Bilirakis (R-FL), GK Butterfield (D-NC), and Mike McCaul (R-TX) introduced HR 1223. Sens. Orrin Hatch (R-UT) and Robert Menendez (D-NJ) introduced S 1509.

Say Thanks to Supporters

Too often we forget to thank those elected officials who support proposals of importance to the PKD community. The following Senators and Members of Congress have cosponsored either the OPEN Act or the Living Donor Protection Act since the previous newsletter. If any of them represent you, please say “thank you” the next time that you contact them.

HR 1270, Living Donor Protection Act
Rep. Jim Costa (D-CA).

Last month we reported that Rep. Terri Sewell (D-AL) and Rep. Jim Clyburn (D-SC) were new sponsors – this is due in large part to the work of the PKD Foundation and our collaboration with former Congresswoman Karen Thurman (1993-2003) who worked on our behalf to secure these key supporters. Thank you Rep. Thurman for your tireless work on behalf of PKD patients everywhere!

Stay Alert

When the time comes, we will ask PKD advocates to immediately contact their elected officials to protect your interests. Your voice needs to be heard.

PKD Kidney Transplant: 2-Staged Procedure Offers Better Outcome, VICTOR Act for Transplants

Kidney Transplant

From Journal of American College of Surgeons 

Kidney Transplant With and Without Native Nephrectomy for Polycystic Kidney Disease: Results of the National Inpatient Sample and the Rationale for a 2-Staged Procedure

Abstract

Background

Polycystic kidney disease (PKD) is one of the most common causes of end-stage renal disease requiring hemodialysis or transplantation. In patients requiring transplant, there are several indications for native nephrectomy, including recurrent cyst infection, bleeding, or to provide room for the graft. There is disagreement about whether it is advisable to perform kidney transplant alone (KT), or to perform kidney transplant with simultaneous native nephrectomy (KTN). We compared postoperative outcomes of KTN and KT in a large national cohort.

Study Design

The Nationwide Inpatient Sample (NIS) between 2000 and 2014 was examined for a diagnosis of PKD with evidence for KT or KTN. Logistic regression, adjusting for age, sex, comorbidity, and hospital region, was used to compare groups for the need for blood transfusion, the need for critical care interventions, and the development of postoperative complications.

Results

A total of 4,003 hospitalizations were identified, which was representative of 19,302 weighted discharges nationally. In adjusted logistic regression models, KTN demonstrated significantly higher risk for blood transfusion (OR 2.06, 95%CI [1.44, 2.96], p<0.0001), postoperative complications (OR 1.44, 95%CI [1.05, 1.96], p=0.02) and critical care interventions (OR 1.44, 95%CI [1.07, 1.95], p=0.02). Other significant predictors for blood transfusion included female sex (OR 1.76, 95%CI [1.45, 2.13], p<0.0001), age over 61 years (OR 1.60, 95%CI [1.21, 2.10], p=0.001) and Charlson comorbidity score ≥2 (OR 1.52, 95%CI [1.10, 2.09], p=0.01).

Conclusions

Among patients with PKD, in comparison to KTN, KT-alone represents a decreased risk for negative postoperative outcomes. A 2-staged procedure should be considered, when feasible, to minimize adverse patient outcomes.

From Knox News, Knoxville, TN, by Terrence Jay O’Neil, Guest column

VICTOR Act would greatly improve lives of veterans with kidney failure

Imagine it’s 5:30 in the morning and you have to be at the clinic by 6:30. You had a pretty good day yesterday. Not too much achiness or shortness of breath, and you slept fairly well last night. You bolt down a light breakfast, get in your car and drive the 20 miles to the dialysis clinic you go to three times a week.

You check in, and after a few minutes you are sitting in a recliner surrounded by other people like yourself with kidney failure. You have two one-eighth-inch-wide needles stuck in your left arm. Those needles are pulling a soft-drink can full of blood out of your body every minute, cleaning it and returning it. You know that you will probably be going home with two bandages over the needle sites to prevent bleeding, feeling tired, nauseated, with muscle cramps and a headache, and you will have to lie down for a good part of the rest of the day to recuperate.

On treadmill for rest of life

Imagine doing that over and over. For the rest of your life. With no hope of getting off the treadmill. Worse, imagine you are an East Tennessee veteran of limited means who served his country faithfully and trusted what you thought were lifelong military health care promises and so you never got commercial health insurance or signed up for full Medicare.

You cannot get off dialysis because you lack means to travel over 300 miles to a VA transplant center in Nashville, Lexington, Ky, or Birmingham, Ala., for transplant evaluation and if you are lucky, the surgery. Because the VA is currently forbidden by law to use money under the CHOICE program for kidney transplants at non-VA facilities, you can’t afford a transplant at the excellent University of Tennessee Medical Center transplant program at Knoxville.


This effectively condemns you and many other East Tennessee veterans with only VA coverage who are potential kidney transplant recipients to dialysis forever.

Transplants a possibility

In May U.S. Rep. Neal Dunn, R-Fla., proposed the Veterans Increased Choice for Transplanted Organs and Recovery Act of 2017, otherwise known as HR 2601, or the "VICTOR Act of 2017”. If approved, this bill would allow many East Tennessee veterans to be evaluated and get on the list to receive kidney transplants at Knoxville. The quality of their and their families’ lives would be dramatically improved. Many could return to work at least half time to help support themselves and their families. Very few of those on dialysis can work to help support themselves because dialysis takes up so much time and dialysis patients just don’t feel well enough to work.

If the VICTOR Act is made law, the government would save money because transplant maintenance is cheaper than dialysis. Each year of hemodialysis costs $85,000. Peritoneal dialysis (another form of kidney failure treatment) costs $60,000. Transplants have a one-time cost of about $120,000 but every year after that maintaining the transplant drops to $30,000. So, after three years, money is saved. Using today’s advanced medications, half of kidney transplants continue to work for 10 years, and a quarter are still working at 20 years. So, the savings can go on for a long time.

If you put yourself in the place of that veteran, you can see why the VICTOR Act is the right thing to do. It improves the quality of the lives of those who have helped defend us. It saves money in the long run. I urge community support through our local legislators the VICTOR Act.

Terrence Jay O’Neil is a retired colonel of the U.S. Air Force Medical Corps

Irrational Kidney Transplant Policy, Tolvaptan Results, Breath Test the Kidney, PKD Blogger Valen Keefer Receives Award

Kidney Transplant

From Washington Post, Opinion: By Marcello Tonelli and John Gill

Our Medicare policy for kidney transplants is totally irrational

Marcello Tonelli is associate vice president of research at the University of Calgary. John Gill is a clinician scientist and professor of medicine at the University of British Columbia and a member of the board of directors for the American Society of Transplantation. They are both former presidents of the Canadian Society of Nephrology.


Kidney transplants are universally acknowledged as the best treatment for kidney failure. Compared with remaining on dialysis, transplant recipients live longer, have better quality of life, are more likely to raise a family, have fewer symptoms and incur far fewer health-care costs.

After a successful transplant, keeping the kidney functional requires lifelong use of immunosuppressive medications, which prevent the recipient’s body from rejecting the new organ. These medications provide excellent value for money since they allow the patient and society to reap the benefits of kidney transplantation.

As researchers from Canada, we’ve studied health care for those affected by kidney disease in the United States and other developed nations. Since 1972, Medicare has provided coverage to patients with kidney failure, regardless of age or disability status. However, while there is no time limit for dialysis patients, kidney transplant recipients who are not otherwise eligible for Medicare lose their coverage 36 months after they receive their transplant — leaving many unable to pay for immunosuppressive medications. Without access to these medications, patients eventually lose their transplants and require dialysis treatment instead.

This policy is irrational, since Medicare has already paid for the kidney transplant and will pay to treat the patient with dialysis — despite its markedly higher cost — when the transplanted kidney fails.

Our research has shown the United States stands alone in allowing this situation to exist. All other wealthy nations recognize the benefits of immunosuppressive medications and cover their costs for patients with functioning kidney transplants.

Funding these medications would save hundreds of millions of dollars annually in direct medical costs. Between 2008 and 2012, the most recent data available, the average annual Medicare cost for a transplant recipient was $22,000 compared with $47,000 for a dialysis patient. But those costs are much higher — at $84,000 — for patients who suffered transplant failure and had to return to dialysis. And if you look at only the patients who died after a transplant failure, average costs skyrocket — to $201,000.

Failing to provide lifelong coverage also dishonors the gift of life made by thousands of kidney donors each year, since denying such access means that some of these gifts will be in vain. We estimate that in the past five years, 7,700 patients have needlessly lost their kidney transplants, 900 patients have prematurely died and Medicare has squandered nearly $1 billion in health-care costs that could have been averted if only funding for immunosuppressive medications had been secured.

Even more frustrating, a legislative remedy — commonly known as “the immunosuppression bill” — is already available. Lawmakers first proposed the bill in 2011, but it has repeatedly stalled.

This bill would allow Medicare-eligible kidney transplant recipients to receive life-saving immunosuppressive medications for as long as their transplant continues to function. Ironically, failure to pass this bill into law during the Obama administration may in part be due to its bipartisan support, which gave little political advantage to passing it.

It is impossible to justify continued inaction: The problem and its solution are both straightforward. The machinery required to fund, prescribe and deliver immunosuppressive medications is in place. All that is needed is the political will to pass legislation and allow U.S. patients to benefit.

PKD Research

From MedScape, by Nisha Bansal, MD, MAS

The Latest on Tolvaptan and Kidney Function Decline in Later-Stage ADPKD Patients

Autosomal dominant polycystic kidney disease (ADPKD) now is the fourth leading cause of end-stage renal disease (ESRD). ADPKD develops when the genes encoding polycystin 1 and polycystin 2 are disrupted, which leads to cyst development and eventual destruction of renal parenchyma.

Vasopressin promotes kidney-cyst cell proliferation and fluid secretion; thus, suppression of vasopressin or blockade of a vasopressin receptor may reduce cyst burden and thus improve kidney outcomes. Tolvaptan is a competitive vasopressin receptor antagonist with potential therapeutic applications in ADPKD.
Review of Recent Trials on Tolvaptan and ADPKD

In 2012, the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) trial investigators randomly assigned 1445 ADPKD patients with creatinine clearance >60 mL/min and a total kidney volume of 750 mL or higher to receive tolvaptan versus placebo.[1] The trial found that over a 3-year period, total kidney volume increased less in the tolvaptan group (2.8% per year vs 5.5% per year in the placebo group).

Tolvaptan was also associated with slower decline in kidney function per year compared with placebo. However, the tolvaptan group also had greater rates of adverse events related to aquaresis and hepatic abnormalities, which led to a higher discontinuation rate.[1] In a follow-up study, the investigators found sustained beneficial effects with tolvaptan use on estimated glomerular filtration rate (eGFR) 2 years after the completion of TEMPO.[2]

In a recent issue of the New England Journal of Medicine, the authors of the REPRISE (Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD) trial studied the effects of tolvaptan on kidney function among ADPKD patients with more advanced kidney disease, defined as eGFR of 25-65 mL/min/1.73 m2 (mean eGFR, 41 mL/min/1.73 m2).[3]

The study had 1496 patients enter a single-blind tolvaptan period. The 1370 patients who were able to tolerate tolvaptan without adverse effects were randomly assigned to receive either tolvaptan (doses of 90-120 mg/day) versus placebo. Randomization was stratified according to baseline eGFR, age of the patient, and total kidney volume.

Overall, characteristics of patients at baseline were balanced between the two groups. Most patients assigned to the tolvaptan group, and who completed the trial, were taking 90 mg morning and 30 mg afternoon doses daily.

At 1 year, the mean change in eGFR (with adjustment for the trial duration for each patient) was -2.34 ± 0.24 mL/min/1.73 m2 in the tolvaptan group compared with -3.61 ± 0.24 mL/min/1.73 m2 for the placebo group, which was statistically significant. Overall, the difference in eGFR decline at 1 year between the groups was 1.27 mL/min/1.73 m2. Per the investigators, a change of this magnitude could potentially extend time to ESRD from 6.2 to 9 years in this population.

When examining subgroups, the beneficial effect of tolvaptan on eGFR change was not statistically significant among patients >55 years of age, those who were not white, or those with stage 2 chronic kidney disease (CKD).

It should be noted that the rates of serious adverse effects were higher in the tolvaptan group (12.5% vs 8.8%), and rates of liver-related events were particularly high (10.9% vs 5.3%). The discontinuation rate of the study drug was also higher in the tolvaptan group (9.5% vs 2.2%).
Findings From the REPRISE Trial—Where Do We Stand?

So what does this trial tell us? The findings from REPRISE suggest that among a younger population of ADPKD patients with moderate CKD, who could tolerate tolvaptan without an unacceptable level of side effects, there was a net difference in eGFR decline of 1.27 mL/min/1.73 m2 over 1 year compared with patients taking placebo.


A significant limitation in the study design was the use of a continuous eGFR outcome (which is "noisy" and can be less precise) rather than a "hard" outcome such as 50% decline in eGFR or ESRD. It remains to be seen whether the benefit is sustained after 1 year and whether tolvaptan affects total kidney volume. Finally, the overall risks (in terms of tolerability and adverse effects) versus benefits will need to be carefully considered before starting tolvaptan in patients with late-stage ADPKD.

From Journal of American Physiology Society, by Lisa M. Guay-Woodford

Murine models of polycystic kidney disease: molecular and therapeutic insights

Abstract

Numerous murine (mouse and rat) models of polycystic kidney disease (PKD) have been described in which the mutant phenotype results from a spontaneous mutation or engineering via chemical mutagenesis, transgenic technologies, or gene-specific targeting in mouse orthologs of human PKD genes. These murine phenotypes closely resemble human PKD, with common abnormalities observed in tubular epithelia, the interstitial compartment, and the extracellular matrix of cystic kidneys. In both human and murine PKD, genetic background appears to modulate the renal cystic phenotype. In murine models, these putative modifying effects have been dissected into discrete factors called quantitative trait loci and genetically mapped. Several lines of experimental evidence support the hypothesis that PKD genes and their modifiers may define pathways involved in cystogenesis and PKD progression. Among the various pathway abnormalities described in murine PKD, recent provocative data indicate that structural and/or functional defects in the primary apical cilia of tubular epithelia may play a key role in PKD pathogenesis. This review describes the most widely studied murine models; highlights the data regarding specific gene defects and genetic modifiers; summarizes the data from these models that have advanced our understanding of PKD pathogenesis; and examines the effect of various therapeutic interventions in murine PKD.

Kidney Failure Detection

From WINK-TV, Southwest Florida

Breath test could provide non-invasive detection of kidney failure

It is one of the top ten leading causes of death and affects five million people in the U.S. Now, doctors at the Cleveland Clinic are testing a new, non-invasive way to detect kidney failure.

Doctors can test your blood and urine for diseases, but now a new device is allowing them to test your breath.

Raed Dweik, MD, Director of Pulmonary Vascular Program at Cleveland Clinic explained, “If you can do it at the side of the road, you can do it anywhere.”

He believes that you can see the health of a patient through their breathprint.

“Anything that is potentially volatile in our blood comes up in the lung and can be measured in exhaled breath,” continued Dr. Dweik. Such as kidney failure.

A healthy kidney gets rid of wastes and toxins in a person’s blood. When the kidneys are not functioning properly, they can cause kidney stones and possibly death. Dr. Dweik and his team are trying to prevent this, by testing for kidney failure using a breathalyzer. In a study of patients with kidney failure and healthy volunteers, he was able to identify five volatile organic compounds in the breath of patients with kidney failure. The device is still being analyzed before it goes to clinical trials.

Researchers also plan to study the effects of dialysis on kidney failure patients’ breathprint. Dr. Dweik has worked on other breath test studies as well, developing breath tests for asthma, heart failure, liver disease, and obesity.

BACKGROUND

Ten percent of the population worldwide is affected by chronic kidney disease (CKD), and millions die each year because they do not have access to affordable treatment. Over 2 million people worldwide currently receive treatment with dialysis or a kidney transplant to stay alive. High blood pressure and diabetes are the main causes of CKD. Almost half of individuals with CKD also have diabetes and/or self-reported cardiovascular disease. More than 661,000 Americans have kidney failure and of those, 468,000 individuals are on dialysis and roughly 193,000 live with a functioning kidney transplant. Kidney disease often has no symptoms in its early stages and can go undetected until it is very advanced. This is the reason it is often referred to as a “silent disease.” Each year, kidney disease kills more people than breast or prostate cancer. In 2013, more than 47,000 Americans died from kidney disease.

CURRENT TREATMENTS

If your kidneys can’t keep up with waste and fluid excretion on their own and you develop complete or near-complete kidney failure, you have end-stage kidney disease. At this point, dialysis or a kidney transplant is recommended. Dialysis artificially removes waste products and extra fluid from your blood when your kidneys can no longer do this. A kidney transplant involves surgically placing a healthy kidney from a donor into your body. The patient will need to take medications for the rest of his/her life to keep the body from rejecting the new organ. For some who choose not to have dialysis or a kidney transplant, a third option is to treat kidney failure with conservative measures. There has been recent development of a disease-detecting breathalyzer that can potentially identify 17 different diseases. “One of the major challenges in the modern era of disease diagnosis is how we can detect the disease when we are still feeling healthy,” says Hossam Haick of the Technion-Israel Institute of Technology. This device is capable of catching a disease in the early stages and may even be able to predict people that are at high risk for certain conditions. Researchers identified more than 100 other chemical compounds exhaled in each breath, 13 of which were associated with certain diseases.

BREAKTHROUGH RESEARCH

Researchers at the University of Washington Health Sciences/Medicine are creating and manipulating mini-kidney organoids that contain a realistic micro-anatomy that tracks the early stages of polycystic kidney disease (PKD). The organoids are grown from human stem cells. By substituting certain physical components in the organoid environment, cyst formation can be increased or decreased. The team found that PKD mini-kidneys grown in free-floating conditions formed hollow cysts that were very large. These cysts could easily be seen. In contrast, PKD mini-kidneys attached to plastic dishes stayed small. According to Nelly Cruz, research scientist, other manipulations to the organoid affects the progression of the disease. “We’ve discovered that polycystin proteins, which are causing the disease, are sensitive to their micro-environment. Therefore, if we can change the way they interact or what they are experiencing on the outside of the cell, we might actually be able to change the course of the disease.”

PKD Life

From Auburn Journal

Auburn resident gets award for giving back

After receiving a kidney transplant 15 years ago, one Auburn resident was chosen for a national award. 

Valen Keefer was chosen for the Bounce Back Give Back award from the Chris Klug Foundation, an award for people who live exceptional lives post transplant. 

The awards recognize two transplant recipients who exhibit an exceptional post-transplant quality of life, whether it is a career accomplishment, participation in a sport or hobby, or simply leading a fulfilling life with family and loved ones. 

“There is something very touching and serendipitous to all of this,” Keefer said. “I was just diagnosed with a rare autoimmune disease — primary sclerosing cholangitis (PSC). This disease, in which there is no treatment or cure, is the same disease that Chris Klug has that led to him needing a liver transplant and will ultimately lead to me needing a liver transplant, too. I was diagnosed with PSC after being selected for this award. The opportunity to meet Chris could not have come at a better time in my life.”

More than 65 nominations representing individuals from 24 states were received for this year’s awards. A team of CKF reviewers selected the two award winners. The two honorees and one guest each will enjoy an all-expense-paid trip to Aspen for the award ceremony on Dec. 8. 

Keefer has demonstrated a commitment to spreading the word about polycystic kidney disease (PKD) and advocating for organ transplantation, while honoring her donor. 

After being diagnosed with PKD at age 10, Keefer battled serious health complications until receiving a lifesaving kidney transplant at age 19. Since that time, she has dedicated her life’s work to being an ambassador for the cause. 

As a blog writer for the PKD Foundation Keefer has published more than 210 articles. She is a founding committee member of the Sacramento chapter of the PKD Foundation, Corks for a Cure event and has spoken at more than 90 different gatherings, reaching thousands of people. Awarded the 2012 Outstanding Media Ambassador for Sierra Donor Services, Keefer’s efforts include an extensive list of volunteer and professional accomplishments including being the subject of an award-winning biography and selected as one of the 12 Most Inspiring Women of “20 Million in 2012” by Donate Life America. 

“I believe we can always find the good in life and I hope you’ll help me spread my message of positivity, this award announcement, and also the beauty of the gift of life with your readers,” Keefer said. “Despite all of the health challenges I face, I continue to bounce back and give back through it all. “

10 Month Old Girl with PKD Needs Kidney; PKD Research: Aquaporin-11, Social Media Reconnects Kidney Sisters

Gift of Life

From WNEM-TV, CBS Affiliate, as reported from CNN

10-month-old Michigan girl born with rare kidney disease waits for transplant

A Michigan couple is counting their blessings this holiday season as they prepare for their daughter's first Christmas, and they're hopeful their little girl will soon receive a life-saving kidney transplant.

The moment a mother meets her child is unforgettable.

"It's just indescribable how much love and how much pain you feel when she feels pain,” said mother Emily Payne.

Payne waited six days to hold her baby girl for the first time.

"They really pushed for us to be able to hold her that day because they knew she was going to surgery and they didn't know if she would make it through that,” Payne said.

Born with autosomal recessive polycystic kidney disease (ARPKD), Rilynn Rose had both of her kidneys removed when she was just a week old.

"So many people told us she wouldn't survive and she's just really overcome everything. She's just really known as a miracle child,” Payne said.

Now 10 months old, this miracle baby is hooked up to a dialysis machine 12 hours a day.

"And then this one is her catheter for dialysis right here,” Payne said.

With each dialysis treatment, Rilynn runs the risk of an infection.

"You think you're safe and then all of the sudden you're not,” Payne said.

Rilynn is about two months and two pounds shy of being eligible for a kidney transplant.

"She's got a whole life ahead of her and she's already going through a lot more than I ever have,” said Zach Payne, Rilynn’s dad.

The emotional and financial toll is a struggle, though.

To become her daughter's full-time nurse, Emily quit her job at the Secretary of State's Office, where people decide whether to be an organ donor.

"I just wish I could go back and share her story and share that we could give her such a better life if you could donate,” Payne said.

One checked box could save Rilynn's life.

The Payne family has partnered with the Children’s Organ Transplant Association to help raise money for the life-saving transplant. >>Click here to donate<<




From Stanford Medicine, Scope Blog

Former co-workers reconnect via social media and become ‘kidney sisters’

Robbie Turner was only 28 years old when she was diagnosed with polycystic kidney disease — a genetic disorder that causes clumps of cysts to form in the kidneys, reducing their function over time. She knew she’d need a kidney transplant one day, and for many years, Turner and her husband thought he would be her kidney donor as he’d been approved as a perfect candidate.

Then Turner’s husband was diagnosed with cancer, and suddenly the couple was grappling with a cancer diagnosis and the need to identify a new kidney donor. Turner had kept her health condition private for years, but now that she needed to find a kidney donor fast, she broke her silence and turned to social media. A recent Stanford Health Care blog explains:

[A co-worker] created a Facebook page, ‘A Kidney for Robbie Turner,’ and uploaded videos of Turner telling her story. By casting her net beyond the people in her immediate social circle, Turner had 12 individuals come forward to be donors. One was a former co-worker, Nona Reid, who still lived in the Dallas area. She and Turner had lost touch for more than 15 years, but had recently reconnected via Facebook.

“I was the number one match, but the only one who lived out of state,” Reid said. She flew to California for testing and evaluation and was approved as a kidney donor for Turner.

On March 22, Turner and Reid were taken into surgery. Marc Melcher, MD, a Stanford Health Care transplant surgeon, performed both of their kidney surgeries. By the end of the day, Turner had a new, healthy kidney.

“I am extremely blessed to have Nona as a friend and I’m grateful and awed by her gift of life for me,” Turner said after the surgery. “She is my ‘kidney sister.’ I will take the best care of this kidney as if I was taking care of her.”

PKD Research

From ScienceDirect
Proteomic analysis of AQP11-null kidney: Proximal tubular type polycystic kidney disease

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the mutation of polycystins (PC-1 or PC-2), in which cysts start from the collecting duct to extend to all nephron segments with eventual end stage renal failure. The cyst development is attenuated by a vasopressin V2 receptor antagonist tolvaptan which, however, will not affect proximal tubule cysts devoid of V2 receptor. Aquaporin-11 (AQP11) is expressed selectively in the proximal tubule of the kidney and AQP11-null kidneys have a disruptive PC-1 trafficking to the plasma membrane to develop polycystic kidneys. Here, we analyzed AQP11-null kidneys at the beginning of cyst formation by quantitative proteomic analysis using Tandem Mass Tag (TMT). Among ~ 1200 identified proteins, 124 proteins were differently expressed by > 1.5 or < 0.8 fold change. A pancreatic stone inhibitor or a growth factor, lithostathine-1 (Reg1) was most enhanced by 5 folds which was confirmed by western blot, while mitochondria-related proteins were downregulated. The identified proteins will be new target molecules for the treatment of proximal tubular cysts and helpful to explore the functional roles of AQP11 in the kidney.

1. Introduction

Human Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the mutation of polycystin-1 (PC-1) or polycystin-2 (PC-2) [1–3]. Cysts originate from the collecting duct in PC-1 null mice with defective cAMP signaling [1], which are marginally attenuated by a V2 receptor antagonist, tolvaptan [4]. Since V2 receptor is absent in the proximal tubule, tolvaptan will not affect the growth of proximal tubular cysts. Moreover, the mechanism for cyst development in the proximal tubule may not be same as in the collecting duct. The therapy against proximal tubular cysts will improve the suboptimal efficiency of tolvaptan therapy for ADPKD [4].

Aquaporin-11 (AQP11) is a new member of aquaporin family which is expressed at the membrane of intracellular organelles such as the endoplasmic reticulum (ER) [5–8]. Currently, the function of AQP11 is not clear even as a water channel due to its unusual location in the cell. However, AQP11-null mice revealed a striking phenotype of intracellular vacuole formation in the proximal tubule at one week old [5,9] indicating its critical role in the proximal tubule development. Surprisingly, these cells subsequently turn to cystic epithelia to develop polycystic kidney disease (PKD) at three week old and death at one month old [5]. The mechanism for the development of PKD in AQP11-null mice may not be related to its water channel function.

Our recent study on AQP11-null mice revealed a trafficking defect of PC-1 to the plasma membrane due to its abnormal glycosylation at the ER [10] possibly induced by abnormal environment of the ER with defective water and/or solutes transports. Irrespective of its mechanism, AQP11-null mice will be a good model for ADPKD affecting the proximal tubule selectively with intact collecting ducts, which will be useful to examine the proximal tubular cyst formation in ADPKD. As is the case with conditional knock-out mice of PC-1 [11], the effect of AQP11 deletion is also developmentally dependent as cysts were not observed with the disruption of AQP11 at ten days after birth [9]. Furthermore, these cysts may represent a very early stage of the cyst formation as they are in fact not cysts but dilated proximal tubules [9].

To expand our previous microarray studies [12], we employed a proteomic approach in this study to compare the differentially expressed proteins in AQP11-null kidney to identify key molecules for the development of proximal tubule specific cysts and functional role of AQP11 in the kidney. [Read more]

Kidney Donation by Tri-athlete, An 8 Person Gift of Life Chain

Kidney Donation

From The Bellingham Herald, via Bend, Oregon

Kidney donation doesn't stop Bend triathlete from competing

Greg Sabin isn't afraid to admit it. He's not exactly the most patient person. So when his doctor told him it'd be at least six weeks after he donated a kidney before he could crank up his workout routine to its usual intensity, he wasn't thrilled.

"I want to be good as gold straight out of the gate," said the 56-year-old Bend resident. "I never really had surgery before, so I didn't really know what to expect."

Sabin didn't swim for a while. He kept his runs short and not too fast. Then, exactly five months after the surgery, he completed a triathlon in Sunriver: a 1.2-mile swim, 58-mile bike ride and 13-mile run.

In January, Sabin donated one of his kidneys to his wife, Stacey, who has a genetic condition called polycystic kidney disease. It causes water-filled cysts to crowd the kidneys and liver, eventually impairing their function. Both of their recoveries have gone smoothly.

Now that Sabin is back in his normal routine — not to mention training for another triathlon — he hopes his experience can be a lesson for others who are hesitant about kidney donation, perhaps fearing it will hamper their athletic performance.

"There was never even a second that I thought that I would accept being less active than I was before," he said, "and I still won't."

Transplant specialists say there's no reason living kidney donors can't continue being competitive athletes, including running in marathons or even ultramarathons.

Dr. Charles Modlin, a kidney transplant surgeon with the Cleveland Clinic, said that's an important message to get out, as living donors are crucial. Not only are there not enough kidneys to go around from deceased donors, transplants from living donors typically have the best outcomes.

"There are a lot of misconceptions that if you donate a kidney, you can't live out your life normally, and you're going to be infirm," Modlin said. "That's just not the case."

'Drink to thirst'

There are, however, important caveats to consider.

Dr. Kayvan Roayaie, an assistant professor of surgery in the division of abdominal organ transplantation at Oregon Health & Science University, said after someone donates a kidney, it's "critically important" to preserve their remaining kidney function.

That means if people plan to engage in intense exercise, they should make sure they're staying hydrated and allowing time for their incisions to heal. Roayaie, who removed Sabin's kidney, said he typically counsels people to wait at least six weeks before vigorous exercise to allow the scar over the abdominal wall — where the surgeon enters to remove the kidney — to develop adequate scar tissue.

Working those muscles too hard before the incision heals enough can lead to hernias, which is when an organ pushes through an opening in the muscle that holds it in place. Abdominal hernias are the most common type.

Sabin said he's noticed he's had to drink more water after the surgery compared with before to avoid cramping during exercise. He also drinks more water over the course of a normal day.

Doctors interviewed for this article said they don't necessarily recommend kidney donors increase their water intake beyond normal, unless they were dehydrated before the surgery. In follow-up exams, Roayaie said doctors will check the moisture of donors' mucous membranes and the turgor of their skin.

After someone donates a kidney, the remaining kidney actually enlarges to compensate and provides between 70 to 80 percent of the total function both kidneys previously contributed together, Modlin said.

"So they don't have to drink an excessive amount of fluid," he said. "Just drink to thirst."

'Extreme stress on the body'

One of the big differences Sabin said he noticed between the triathlon he performed in June and previous races was his energy level wasn't as high as it used to be. As a result, his time was slower than he would have liked.

Fatigue is almost a universal experience for kidney donors, Roayaie said. Typically, they're back to their usual energy levels about a month after the surgery.

"Surgery, even for a healthy person, is an extreme stress on the body," Roayaie said. "The body is pouring a lot of that energy into healing and creating new scar tissue, and that all of that contributes to the fatigue."

As far as completing a triathlon five months after the surgery, Roayaie said he's not surprised Sabin noticed the effects. There are still changes happening in the body within the first year after donation, he said.

It takes four to eight months for the remaining kidney to enlarge to compensate for the missing one, so it's possible that put a damper on Sabin's performance, Modlin said. It could also be he wasn't able to train as hard as he usually does, he said.

"It's remarkable that he was able to do it," Modlin said.

OHSU performs extensive testing on living donor candidates to ensure their bodies can handle the shock. Diabetes and hypertension are the most common conditions that disqualify people from donating, Roayaie said.

Before he was approved to donate, Sabin said doctors were alarmed by his scores on some of their tests. When his heart rate came up as 43, for example, they suspected a heart condition. He was able to convince them that's just his normal resting heart rate.

"They didn't know what to do with it," he said.

Risk low, but not zero

While extensive research has been done on how transplant recipients fare after getting a new kidney, less is known about living donors.

The United Network for Organ Sharing, a nonprofit organization that manages the nation's organ transplant system through a contract with the federal government, requires all transplant centers, like those at OHSU and Cleveland Clinic, for example — to follow up with living organ donors for at least two years. Hospitals are required to send UNOS data on donors' kidney function and whether they had any hospitalizations, organ failures or deaths. Providing the information is voluntary on the patient end.

The risk to donors is low, but it's not zero, said Dr. David Klassen, UNOS' chief medical officer. In the same way as getting one's appendix removed, there's always a small risk of death. For kidney donors, the risk of death is about three in 10,000 people, he said. Another roughly 30 in 10,000 people develop kidney failure after donating a kidney.

"That's fairly small," said Klassen, also a nephrologist. "But again, there have been lots of living donors over the years. To the extent we've been successful in collecting that information, we have a fairly solid understanding of what the risks are."

A partner organization to UNOS, the Scientific Registry of Transplant Recipients, is creating a living donor registry in hopes of tracking donors longterm.

'You can still participate'

For her part, Stacey Sabin said with a laugh that getting her husband's kidney hasn't motivated her to get out and do a triathlon. Her goal for 2018 is to exercise more.

"I live with an Ironman, so I hear it all the time," she said, referring to the Ironman competitions her husband has participated in.

Insomnia is one of the side effects of the medications she takes to prevent her body from rejecting the kidney, so gathering the energy to exercise has been a challenge. She relies on Facebook groups and other online networks to learn about other people's post-transplant experiences. She's been relieved to learn her side effects are normal.

As for her husband, he's in the throes of training for a half-Ironman competition in St. George, Utah, in May, the same one he did in 2014. His goal is to match his 2014 time. The paved course, which features steep hills carved into the red rock canyon, is the toughest he's ever done.

"I'd like to bring awareness to the fact that you can still participate — and hopefully somewhat competitively — in this stuff after such a thing," he said.

From U.S. News and World Report, By Michael Morella, Staff Writer

U.S. News Sits In as Surgeons Carry Out an 8-Person Kidney Exchange

Four people received new leases on life via the transplant 'chain' at Chicago's Northwestern Memorial Hospital.

Four Chicago-area residents needed kidney transplants but did not have matching donors. At Northwestern Memorial Hospital, they got the organs the required from willing strangers through a kidney transplant chain. (BRETT ZIEGLER FOR USN&WR)

Today, Kevin Condreva will receive a new kidney at Northwestern Memorial Hospital. All told, his transplant will involve surgery on eight people.

Condreva, 22, and his aunt, Donna Spans, 63, are two links in a transplant "chain" that by the end of the day tomorrow will give a new lease on life to four people from the Chicago area. Condreva is actually undergoing his second transplant; he was just 15 when he first noticed blood in his urine and was diagnosed with IgA nephropathy, a common kidney disease that damages the organ's ability to filter waste from the blood. When he was 17, his mom was his donor, but the disease came back. That kidney failed, too.

Spans, who is not a match for her nephew, undergoes surgery here as well – ready to trade one of her kidneys to a stranger so that Condreva can receive one from another stranger and be freed from nightly dialysis. She and the other members of the group won't know who donates to whom as they head into surgery, but Spans' kidney will go to Patricia Tripolitakis, 51, who has polycystic kidney disease. Her husband, Leo, 51, is donating to Lee Jenkins, 53, whose wife, Lorretta, 46, is giving a kidney to Steven Boone, 46. Condreva's donor, a good Samaritan who prefers to remain anonymous, turned up as a match for him just a few weeks earlier and set the chain in motion. Later, Maggie Swanson, a friend of Boone's who wanted to help him but wasn't a match, will donate a kidney to someone else in need – potentially starting a new chain.

Such "paired exchanges," first performed in the U.S. at Rhode Island Hospital in 2000, have taken off in the last seven years or so as a way to shorten what can otherwise be a long wait for a healthy kidney. Some 97,000 people are now on the waiting list maintained by the United Network for Organ Sharing, a nonprofit that manages the federal organ transplant system; the average wait time is generally about three to five years. That's too long for many people: About 12 die each day as they hope for a kidney to turn up. A swap like this one effectively fast-tracks the process. At Northwestern, the period between joining the exchange program and surgery typically varies from about two to six months depending on the difficulty of matching.

Today, 20 to 30 percent of living donor kidney transplants here are done through the paired exchange program, mostly in four- to eight-person swaps. Each week, clinicians run a computer program to explore potential matches from among the incompatible pairs in the system. "There are actually multiple potential solutions that we can look through," says John Friedewald, a transplant nephrologist and medical director of the kidney transplant program. Northwestern also participates in the UNOS kidney paired donation program, which includes roughly 250 paired donors and candidates across the country. The National Kidney Registry, another nonprofit organization, facilitates hundreds of exchanges a year nationwide. In 2015, the NKR organized the longest swap to date, a 70-person chain involving teams at 26 hospitals.

By about 7:30 a.m. on the morning of the surgery, Condreva's donor and Spans are in separate operating rooms. Surgeons use a minimally invasive approach, making a series of incisions about the size of a centimeter through which they insert instruments and a tiny camera to guide their work; the kidneys are extracted through a slightly larger cut. The minimally invasive technique has "made the idea of donating a less scary undertaking" because it's safer than open surgery and recovery is much more rapid, says Joseph Leventhal, who directs the kidney and pancreas transplant programs and is performing several of this week's procedures.

By late morning, Condreva and Patricia Tripolitakis are sedated and in the OR. Their surgeons make a long incision across their lower abdomens and patch each new kidney into its blood supply and the ureter, the tube that moves urine from the kidney to the bladder. Before long, the transplanted organs are working fine. Later that day, Condreva and Tripolitakis are up and moving gingerly around the hospital floor.

A match depends largely on blood type and the presence of antibodies, proteins in a recipient's immune system that guard against foreign viruses and bacteria and can cause the system to reject a kidney even from a donor whose blood type matches. Such was the case for Condreva and Spans, who both have Type A blood and initially were a match. They became incompatible because Condreva developed resistance to his aunt – likely a result of several blood transfusions and the transplant from his mom, Patricia, who is Spans' sister. [Read more]

PKD Impact Scale, Artificial Kidney Update, Tesevatinib Phase 2 Clinical Trial

Artificial Kidney

From Wonderful Engineering, by Ali Vaqar

This Artificial Kidney Eliminates The Need For Kidney Dialysis

It is estimated by The National Kidney Foundation that over 100,000 patients are on the waiting list for kidney donors. A further 3,000 names are added to the list every year. An average patient has to wait for 3.6 years for a viable transplant. The patients are treated with dialysis while they are waiting for a transplant and only one in three patients survive for more than five years without a transplant. All that could change as scientists have developed the world’s first artificial kidney.

This bio-hybrid uses living kidney cells along with a series of specialized microchips powered by the human heart to filter waste from the blood-stream. The artificial kidney can bypass the complication of matching donors and tissue rejection. To address this unmet need, William Fissell from Vanderbilt and Shuvo Roy from the University of California, San Francisco (UCSF) launched The Kidney Project.

“We can leverage Mother Nature’s 60 million years of research and development and use kidney cells that fortunately for us grow well in the lab dish, and grow them into a bioreactor of living cells,” explained Fissell in a recent article published by Research News Vanderbilt. Fissel claims that it can reliably distinguish between waste chemicals and the nutrients that need to be reabsorbed by the body.

The artificial kidney can be inserted into the body by a common surgery and has been proved to work efficiently. This kidney has several microchips which are controlled by the heart and removes the toxins from the blood the same way a normal kidney does.

The artificial kidney has 15 microchips built one atop the other and they act as filters. They will hold living renal cells which will eventually grow around the microchips and mimic a real kidney. Engineers are currently working and testing every single detail of the device to make sure the device can safely let the blood run through without the formation of clots or damaging the kidney in any way.

This solution has been working so far and the rejection rate has been zero. The human trials are yet to commence but the research shows promising results and everybody is hoping it might eliminate the need for dialysis.

From Medical Xpress

Small changes to organ procurement system could lead to more life-saving transplants

Slight changes to the system for allocating deceased-donor kidneys could result in higher rates of organ procurement and lead to more kidney transplants across the country, according to new research co-authored by an Indiana University Kelley School of Business professor.

"Any increase in supply will result in saved lives," said Rodney P. Parker, an associate professor of operations management at Kelley. "The lists of patients awaiting a kidney transplantation are lengthy and growing. Many of these patients undergo expensive and inconvenient dialysis treatment while waiting."

Parker and three other researchers studied three risk factors that explain the geographic differences in procuring deceased-donor kidneys across the United States: organ quality, the median wait time for donation and the degree of competition between transplantation centers in the area.

They found an expected annual increase in procured organs ranges from 58 (an increase of 0.5 percent of all procured kidneys) to 174 (an increase of 1.2 percent), depending on regional or national sharing.

In 2015, 87,538 patients with end-stage renal disease died while on dialysis (16.3 percent of all dialysis patients are awaiting kidney transplants), and 18,805 kidney transplantations were performed that same year. The majority, 13,132, came from cadaveric donors.

More than 100,000 people are waiting for a kidney transplant in the U.S, with more than 3,000 patients added to the list each month, according to the National Kidney Foundation.

This study, which appears in the journal Production and Operations Management, is among the first to consider how to increase the supply of procured kidneys, rather than changing demand or considering different ways of allocating a fixed supply.

The researchers analyzed the effects of a 2014 policy change that allows lower-quality kidneys—considered the bottom 15 percent of available organs—to be immediately offered more widely in a region without seeking patients only in the local area.

They found that expanding the geographic range also could save lives of many who currently are less likely to receive a kidney based on where they live.

"The increase in supply is induced by the disparity in patient waiting times across different geographies," Parker said. "Thus, patients in areas with longer waiting times will benefit from this increase without adversely affecting the waiting times in the source areas. Overall, the gap in median waiting times between areas will narrow."

Parker and his colleagues concluded that transplant candidates living in less-populated areas may be more selective about the organ quality because waiting times are relatively short.

"When some cadaveric kidneys of lower quality become available, these kidneys may not be procured since the local patients can simply wait a short period for a superior quality kidney," he said. "However, those lower-quality kidneys would be highly sought in other areas where the waiting times are much longer, such as in California and New York.

"Patients already at the top of the list in the more congested areas (which have longer median waiting times) will already likely have a short time for the next available kidney, so they will likely not accept a poorer quality kidney," he added. "However, someone who is further down the list in these areas may recognize that they face a lengthy wait and be willing to accept such a kidney rather than face the grim prospect of a four-hour dialysis treatment three times per week, not to mention the expense and diminished health."

Cadaveric kidneys are initially made available to those living in one of 58 donor service areas around the country, before being then offered to those in a broader region of several donor service areas and, finally, nationally. Competition among 272 transplant programs across the country also contributes to outcomes.

Fourteen of the 58 donor service areas offered 129 or fewer kidneys in 2009, so if some organs are shared more broadly, then the expected increase in transplants could represent the addition of a small- to medium-sized donor service area. [Read more]

Living with PKD

From American Journal of Kidney Diseases

Development of the Autosomal Dominant Polycystic Kidney Disease Impact Scale: A New Health-Related Quality-of-Life Instrument

Portions of full article.

Background
The impact of autosomal dominant polycystic kidney disease (ADPKD) on health-related quality of life (HRQoL) is not well understood due to a lack of instruments specific to the condition.

Study Design
Content for a new self-administered patient-reported outcome (PRO) questionnaire to assess ADPKD-related HRQoL was developed through clinical expert and patient focus group discussions. The new PRO instrument was administered to study patients with ADPKD to evaluate its reliability and validity.

Setting & Participants
1,674 adult patients with ADPKD participated in this research: 285 patients in focus groups to generate questionnaire content, 15 patients in debriefing interviews to refine the PRO questionnaire, and 1,374 patients to assess the performance and measurement properties of the PRO questionnaire.

Outcome
A new PRO questionnaire.

Results
The ADPKD Impact Scale (ADPKD-IS), consisting of 14 items representing 3 conceptual domains (physical, emotional, and fatigue) plus 4 additional questions, was developed. The instrument’s reliability (regarding internal consistency and test-retest consistency) and validity (content and construct) were supported.

Limitations
Need for more responsiveness testing when more data from clinical use become available over time. Complex concepts such as ADPKD-related pain and impact on a patient's HRQoL need further evaluation.

Conclusions
The ADPKD-IS is a new patient-centric tool that reliably and validly provides a standardized method for assessing HRQoL and overall disease burden in patients with ADPKD.

Discussion
At the outset of our research, we were faced with discrepant reports of disease burden in ADPKD and its onset based on literature and physician reports versus anecdotal reports through patient foundations and patients. This discrepancy was also observed in the feedback from clinical experts, who may not be aware of patients’ early concerns due to the very intermittent visit schedules in the earlier disease stages, and patients, who may not bring concerns to physicians because they have adjusted to the disease impact on their lives and experiences with trivialization of these concerns by physicians.9 Lack of patient-centric tools to assess ADPKD-related disease burden has led to a knowledge gap for disease stages, giving the impression that the burden of patients with ADPKD is no different from that of the general population (Fig 4).9, 12, 19 New initiatives for further understanding of priorities for different stakeholders, including patients, caregivers, physicians, and researchers (such as Standardized Outcomes in Nephrology [SONG]), have been initiated since we started our research, but to date, they focus on other areas in nephrology, and ADPKD-specific outcome measures have yet to emerge.

The ADPKD-IS is a new tool with support for its reliability (internal consistency and test-retest) and validity (content and construct). The ADPKD-IS is useful for assessing ADPKD-related disease burden across all CKD stages in a cross-sectional cohort, but also tracking disease burden long term.

The physical domain includes 5 items measuring impact on the ability to perform various activities and 2 items measuring impact of disease-associated pain on daily activities. Identification of 3 distinct types of pain led to retention of the existing pain questions as descriptive of the overall pain concept. However, we also proceeded to develop an additional questionnaire specific to ADPKD-related pain.36, 37 The fatigue domain assesses 3 specific features of ADPKD-associated fatigue: general fatigue, tiredness while driving, and fatigue after a good night’s sleep. Items within this domain exhibited higher intradomain correlations than interdomain correlations (Table S3). Therefore, fatigue among patients with ADPKD appears likely to encompass aspects of both emotional and physical burden. The emotional domain assesses the emotional impact of ADPKD via 3 concepts common to many instruments (acceptance, anxiety, and sadness) and a fourth disease-specific item (feeling full before appetite is satisfied).

The ADPKD-IS covers the entire range of health burdens associated with ADPKD across CKD stages in a single instrument, which is not the case for any other PRO instruments. All items were non-normally distributed, and most patients reported at the lower (less affected) end of the range, consistent with the natural history progression of the disease, for which hyperfiltration can compensate for the early loss of kidney tissue, leading to little change in kidney function until decades after birth.1, 2 Individual items also showed limited ceiling effects, indicating the ability of the ADPKD-IS to differentiate between health burdens as patients progress to later stages of the disease, in which HRQoL is more dramatically affected. Consistent with its predicted ability to assess HRQoL across the entire disease spectrum, the ADPKD-IS can show differentiation between disease stages with more sensitivity than general instruments.

Use of properly developed PRO instruments is a key element of drug development programs using patient-focused end points and for characterization of disease-specific burden with increasing importance given the 21st Century Cures Act requirements. We also see the ADPKD-IS as a tool for researchers and health care providers to better understand ADPKD-specific patient burden with potential use as a patient management tool in clinical practice. Access to the full US-English ADPKD-IS questionnaire, its user manual, and other language versions are available via Mapi Research Trust at https://eprovide.mapi-trust.org/.

PKD Research

From Business Wire

Kadmon Initiates Phase 2 Placebo-Controlled Clinical Trial of Tesevatinib in Autosomal Dominant Polycystic Kidney Disease

Kadmon Holdings, Inc. (NYSE:KDMN) today announced that the first patient has been dosed in a Phase 2 clinical trial of tesevatinib in autosomal dominant polycystic kidney disease (ADPKD), an inherited disorder that frequently leads to end-stage renal disease. Tesevatinib is the company’s tyrosine kinase inhibitor.

The randomized, double-blind, placebo-controlled trial builds on findings from Kadmon’s open-label, dose-finding Phase 2a study of tesevatinib in ADPKD, which demonstrated that the 50 mg once daily (QD) dose had an encouraging safety profile and was well tolerated in this population.

The new study is enrolling up to 100 patients, randomized 1:1 to receive tesevatinib 50 mg QD or placebo. The primary endpoint is the change from baseline in height-adjusted total kidney volume at 12 months.

In addition to the ADPKD trial, in September 2017, the first patient was dosed in Kadmon’s Phase 1 dose-finding clinical trial of tesevatinib in patients with autosomal recessive polycystic kidney disease (ARPKD), a rarer, more severe form of the disease affecting newborns and children. There are no FDA-approved therapies for ARPKD and there are no other candidates in clinical trials for ARPKD in the United States.

“Tesevatinib has been shown to inhibit molecular pathways central to the progression of PKD—mediated by its inhibition of the epidermal growth factor receptor (EGFR) and Src family kinases—and also accumulates in the kidneys, making it a promising therapeutic candidate for this disease,” said Harlan W. Waksal, M.D., President and CEO at Kadmon. “We are encouraged by the safety and tolerability findings from our open-label study, and the initiation of these trials signifies an important step in our effort to address this unmet medical need.”

PKD Research: Phase 3 Trial shows Tolvaptan slows decline in kidney function

PKD Research

From Eureka Alert

New findings on tolvaptan as autosomal dominant polycystic kidney disease treatment

Vicente Torres, M.D., Ph.D., discusses new findings on tolvaptan as autosomal dominant polycystic kidney disease treatment

ROCHESTER, Minn. - A phase 3 trial studying the effects of tolvaptan has found that the drug slowed the rate of decline in kidney function in patients with the most common form of polycystic kidney disease, a condition with no cure. The results are published today in the New England Journal of Medicine.

Autosomal dominant polycystic kidney disease is an inherited condition that affects 1 in every 500 to 1,000 individuals in the U.S. This disease is found in all races and sexes.

Autosomal dominant polycystic kidney disease, which is the fourth most common cause of end-stage kidney disease, requires dialysis or kidney transplant.

The disease causes a slow but relentless growth of cysts that damage the kidneys. In addition to negatively affecting quality of life, the condition also causes hypertension and painful complications. The cysts, which can damage kidneys with their size, can develop in other organs, especially the liver.

Approximately half of individuals with autosomal dominant polycystic kidney disease eventually will require dialysis or kidney transplant by age 60. The results of the trial demonstrated tolvaptan's ability to intervene in a way that slows kidney function decline in this population.

"This is the first treatment that targets a mechanism that directly contributes to the development and growth of the kidney cysts in autosomal dominant polycystic kidney disease," says Vicente Torres, M.D., Ph.D., director of Mayo Clinic's Translational Polycystic Kidney Disease Center. "This in effect means it may delay the need for a kidney transplant or dialysis in patients with this disease."

As lead investigator of the trial, Dr. Torres is available for media interviews to discuss these findings and their significance for those facing autosomal dominant polycystic kidney disease.

From Medical Research.com

Vasopressin-Inhibitor Tolvaptan Reduces Kidney Function Decline in Polycystic Kidney Disease

MedicalResearch.com Interview with:

Vicente E. Torres, M.D., Ph.D.
Director of the Mayo Clinic Translational Polycystic Kidney Disease (PKD) Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Experimental work pioneered by Dr. Jared Grantham showed that cyclic AMP, an intracellular signaling molecule, promotes the development and growth of cysts. Vasopressin, a hormone produced by the pituitary gland, stimulates the production of cyclic AMP in the collecting ducts, from which most cysts derive in autosomal dominant polycystic kidney disease (ADPKD). While this effect of vasopressin is necessary for the kidneys to concentrate and reduce the volume of urine, it promotes the development and growth of cysts in patients with ADPKD. Dr. Vincent Gattone realized that inhibiting the action of vasopressin could be protective in polycystic kidney disease. Work in our and other laboratories confirmed that suppression of vasopressin production, release or action reduces cyst burden, protects kidney function, and prolongs survival in rodent models of the disease.

This experimental work provided a strong rationale for clinical trials of tolvaptan, a vasopressin V2 receptor antagonist. Tolvaptan reduced the rate of kidney growth in the TEMPO 3:4 trial, in patients with early ADPKD. It also reduced the rate of decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), from 10.1 to 6.8 mL/min/1.73 m2 over three years. The eGFR benefit was maintained during two additional years when all the patients were treated with tolvaptan in an open label extension of the TEMPO 3:4 trial (TEMPO 4:4). Safety laboratory tests performed every four months showed elevations of liver transaminases in blood in 4.4% of tolvaptan and 1% of placebo-treated patients. Three of 1,271 tolvaptan-treated patients during TEMPO 3:4 and TEMPO 4:4 had evidence of potentially serious drug-induced liver injury. These abnormalities occurred all within the first 18 months of exposure to tolvaptan.

Based on the TEMPO 3:4 results, tolvaptan was approved for the treatment of rapidly progressive ADPKD in Japan, Canada, European Union, Switzerland and South Korea. In the United States, the Food and Drug Administration requested additional data to further evaluate the efficacy and safety of this drug. The REPRISE trial was performed to determine the efficacy and safety of tolvaptan in patients with later stage ADPKD.

What are the main findings?

Tolvaptan reduced the decline in eGFR from 3.61 to 2.34 mL/min/1.73 m2 over one year.
The effectiveness of tolvaptan in lowering the rate of decline in kidney function in REPRISE, in patients with later stage ADPKD (mean age 47 years, mean eGFR of 41 mL/min/1.73 m2), was similar to that previously observed in TEMPO 3:4 in patients with early stage ADPKD (mean age 39 years, mean eGFR 81 mL/min/1.73 m2).
The frequency of liver enzyme elevations was also similar, but there no cases of potentially serious drug inducer liver injury occurred in REPRISE, likely due to more frequent monitoring and earlier interruption or discontinuation of the drug.

MedicalResearch.com: What should readers take away from your report?

Response: The results of REPRISE in patients with later stage ADPKD, together with those of TEMPO 3:4 and TEMPO 4:4 over five years in early stage disease, show that tolvaptan is effective over a broad range of disease and may delay the need for dialysis or kidney transplantation.

Assuming that tolvaptan treatment would continue to slow the decrement in estimated eGFR by 1.27 mL/min/1.73 m2 per year, the time from an eGFR of 41 mL/min/1.73 m2 (average baseline eGFR in REPRISE) to CKD 5 (eGFR of mL/min/1.73 m2) would be extended from 6.2 years to 9.0 years. A larger benefit might be expected if treatment were started earlier.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Post-marketing registries in the countries where tolvaptan has been approved for the treatment of ADPKD to confirm its long-term safety and effectiveness.
Research to understand the mechanisms of the liver toxicity and to test or develop similar drugs without this problem.
New tolvaptan formulations or combinations with other drugs to enhance its efficacy.
New pharmacological strategies targeting cyclic AMP signaling.