- PKD or polycystic kidney disease causes fluid-filled sacs called cysts to grow on the kidneys, creating scarring.
- Most PKD can be traced to specific gene mutations called PKD1 or PKD2.
- About half of people with PDK will eventually progress to end-stage kidney disease and require either dialysis or a kidney transplant.
- At Yale Medicine, patients can take part in clinical trials of new PKD treatments.
- Genetic understanding of PKD and fertility advances can eliminate the disease entirely for future generations.
In May 2014, Annamarie Williams, a social worker in East Haven, celebrated her wedding with 250 guests. But all through the joyous event, her mother, Sally Proto, kept a terrible secret. She'd had polycystic kidney disease (PKD) for two decades and now her kidneys were failing. Her doctor wanted her to start dialysis immediately. “I didn’t tell anyone, because I didn’t want to put a damper on the wedding,” Proto says.
Proto broke the news to her children a few weeks later. “That was one of the hardest things I had to do,” she says. Her two daughters and son, all in their 20s, knew their mother had a problem with her kidneys, but didn’t realize how serious it had become. PKD causes fluid-filled sacs called cysts to grow on the kidneys. These create scars that harm the organs’ function and eventually cause them to shut down.
Distraught, Proto’s children insisted on accompanying her to her next appointment with her nephrologist, Neera Dahl, MD, an associate professor of nephrology at Yale School of Medicine. “She was very good, she answered all of their questions,” Proto says. But Dr. Dahl also shared some information that shocked Williams and her siblings: Because their mother’s condition was caused by a genetic mutation, each of them had a one in two chance of inheriting it.
“I was taken aback,” says Williams, who was 26 at the time. “At such a young age, you never think you’re going to have a disease. I thought, of course we don’t have it.”
But she did.
Inherited kidney disease
Most polycystic kidney disease can be traced to a specific gene mutation. About 85 percent of the time, it is in a gene called PKD1; otherwise, it is usually in the PKD2 gene.
In healthy people, those PKD genes work together. But dysfunction in either gene—which can happen if it mutates—leads to polycystic kidney disease.
The disease is often discovered after an ultrasound or other imaging test shows multiple cysts in the kidneys. “A normal young kidney has no cysts,” Dr. Dahl says. “As we get older, we all have one or two.”
For people with the disease, the cysts can grow to the size of grapefruits, enlarging the organs. The cysts can also lead to high blood pressure at early ages. Over time, the kidneys lose function.
About half of people with polycystic kidney disease will eventually progress to end-stage kidney disease and require either dialysis or a kidney transplant. The disease moves faster in patients with a PKD1 mutation, who often need one of those treatments by the time they reach their 50s. Patients with a PKD2 mutation may make it to their 70s before their kidneys fail
Many people with polycystic kidney disease are aware of their predisposition, because a parent or sibling is also affected. Proto's disease was diagnosed in her 30s after her doctor felt something unusual in her belly during a routine physical. A subsequent ultrasound revealed cysts that were already enlarging her kidneys.
Two daughters learn their fate
Proto’s oldest daughter, Dana Romano, wanted to be tested as soon as possible, and her kidneys were fine. Williams waited a few months, until her next physical, when she told her doctor about her mother’s condition and asked for an ultrasound. The test found cysts. "I cried," she says. "Then I made an appointment with Dr. Dahl."
The doctor reassured Williams. “She told me I needed to start watching my diet and my blood pressure. Then we talked about getting pregnant,” she says. Williams and her new husband had hoped for a family, but she did not want to pass on her PKD1 mutation. “It’s different from my mom, who didn’t know she had the disease before she had her kids,” she says. “It would bother me to know that I could have prevented it.” She met with her gynecologist, who suggested she consider in vitro fertilization (IVF).
For would-be parents with a known genetic mutation, fertility doctors can screen eggs or embryos. This is done via an extra step in the in vitro fertilization process called pre-implantation genetic diagnosis. The potential parents can choose to use only those eggs or embryos that do not carry the mutation. So Williams had a consultation at Yale Medicine Fertility Center. “My IVF doctor told me, ‘You can stop this disease,’” Williams says. “I decided IVF was my best choice.” She and her husband started saving money, because health insurance doesn't cover most of the costs of the procedure.
Immediately after Williams was diagnosed with PKD, her sister promised to donate one of her kidneys to her. Meanwhile, their brother, Dominic Proto, offered to donate a kidney to their mom. He started the screening process and was PKD-mutation free. However it turned out that his liver enzymes were elevated, so he was not a suitable donor for his mother.
Proto is now on the list to receive a kidney donation when one becomes available, and one of her siblings is being tested as a possible donor. In the meantime, Proto gets a type of dialysis called hemodialysis three days a week. “I feel a little fluid starting to build up on the days that I go, but otherwise, I feel pretty good,” she says.
As for Williams, Dr. Dahl suggested she start taking blood pressure medication. A recent study reported that keeping blood pressure at 110 over 70 is beneficial for younger PKD patients with normal kidney function. “It decreases the rate of cyst growth,” Dr. Dahl says.
Patients travel to Yale for PKD treatment
Yale Medicine’s team of experts—nephrology researchers, clinical nephrologists, geneticists, radiologists, and transplant surgeons—cares for more than 200 patients with polycystic kidney disease.
Patients can also take part in clinical trials of new PKD treatments at Yale Medicine, one of a handful of places across the country that offers such opportunities. For a current trial of a drug called Samsca (tolvaptan), “We have people traveling to Yale from as far away as South Carolina and Florida,” Dr. Dahl says. “We have engaged in trials with medications that may slow cyst growth, and we are actively exploring the role of kidney scarring in PKD.”
Other PKD patients come in from New York and other parts of New England for monitoring and treatment. Yale Medicine’s highly specialized team gives them the care they need.
“PKD doesn’t get better or go away,” Dr. Dahl says, “but it can be effectively managed.”
And for families such as Sally Proto’s, with the help of clinical research, genetic understanding and fertility advances, the disease can be eliminated entirely for future generations.
To learn more about clinical trials for treatment of PKD, visit.