One day in 2022, Karen Boyd read a magazine article that not only caught her attention but moved her to action. The steps she took during the next two years had a powerful effect on her own life, but they may also help to change the lives of millions of others.

The article she read in PKD Life, a quarterly publication from the non-profit PKD Foundation, concerned a study at UCHealth University of Colorado Hospital that pointed to the importance and possible effectiveness of weight loss in slowing the progression of autosomal dominant polycystic kidney disease (ADPKD). It’s a genetic condition that causes fluid-filled cysts to crowd and enlarge the kidneys and decrease their function, often dangerously. For now, there is only a single FDA-approved drug, tolvaptan, to slow the growth of kidney cysts and the decline of kidney function in ADPKD.

Boyd has plenty of experience with ADPKD. Like many others, she had experienced no symptoms when she was diagnosed with the disease nearly 20 years ago. She inherited it from her father. He had received a kidney transplant — thanks to his wife who served as his living donor – that gave him 14 additional years of life before he died. Boyd estimates that 20 other family members have ADPKD.

“The study really hit home for me,” said Boyd, a successful real estate agent from Downingtown, Pennsylvania, about 45 minutes northwest of Philadelphia. “I’ve seen many family members suffer through disease complications, dialysis, finding donor matches, getting through daunting transplant surgery and early death.”

A call to action to fight ADPKD with effective treatments

Boyd learned from the article that the weight loss research in Colorado that she had read about was a pilot that had been led by Dr. Kristen Nowak, associate professor of Medicine in the Division of Renal Diseases and Hypertension at the University of Colorado School of Medicine. Nowak had also collaborated with division colleague Dr. Katharina Hopp, an associate professor and PhD researcher, on a promising preclinical trial centered on ADPKD and weight loss in mice.

The article not only captured Boyd’s attention, it led her to action. She learned that Nowak was leading a new, larger study that again focuses on whether weight loss can slow kidney cyst progression in people with ADPKD. She made a quick decision.

“I stood up from my couch, walked to the desk, got my phone and called to get involved,” Boyd said. She reached Diana George, a study coordinator working with Nowak. Boyd enrolled in the new, two-year trial, completed it and has made lifestyle changes that she believes have set her on a path to better health. More on that later.

Examining the role of calorie restriction in slowing ADPKD

The current trial further probes the effectiveness of a particular weight loss strategy, calorie restriction, in slowing or even halting kidney growth in patients with ADPKD and secondarily reducing the volume of “abdominal adiposity,” or belly fat, which Nowak said may promote inflammation and drive the growth of kidney cysts.

The trial centers, as the pilot did, on providing behavioral and lifestyle education to obese and overweight individuals with ADPKD as a way to lose weight. Participants are divided into two groups. The control group gets only an initial consultation with a registered dietitian about healthy nutrition and recommendations for managing ADPKD. The other group, to which Boyd was assigned, enters a program designed to restrict their calorie intake by approximately 35% over two years. Participants from across the United States remotely attend group behavioral weight-loss classes, led by a registered dietitian who provides education and counseling. Participants also regularly relay information about their blood pressure, weight, and diet choices, which they record in food journals.

In addition, people in both groups get MRI tests to measure their total kidney volume and submit blood and abdominal tissue fat samples to measure biological changes at the beginning and end of the study. Nowak said providing the tissue fat samples is optional, but that about 90% of enrollees thus far have agreed to do so.

Improvements in the new ADPKD weight loss trial

The current NIH-funded trial builds on the promise of the pilot trial’s findings while also addressing its limitations. For example, the pilot compared calorie restriction and intermittent fasting as strategies for losing weight. Both were effective, but individuals lost more weight and did a better job of sticking with a calorie-restricting regimen. That finding provided the basis for focusing on calorie restriction in the current study, but Nowak pointed to a broader and important take-away.

“It seemed to matter less how people approach dietary weight loss [but rather] how much weight they lost,” she said. “That was the predictor of kidney growth. We saw a very strong association that the people who lost the most weight had the slowest growth, or even non-growth, of their kidneys.”

Still, the pilot lacked a control group of patients and therefore could not substantiate that it was weight loss that caused kidney growth to slow. A companion trial of mice led by Hopp, however, provided key support for the present trial. Her work compared mice with ADPKD who were placed on calorie restriction, intermittent fasting and time-restricted feeding regimens with a control group who ate as they desired. The conclusion: only those with restricted calorie intake lost “significant” weight and had slower kidney cyst growth.

In addition to establishing a control group, the current study is much larger and, at two years, twice the length of the pilot. It aims to enroll 126 participants, roughly quadruple the number of its predecessor, Nowak said. It will also analyze the fat samples taken from participants in search of clues, such as changes to immune cells, that may restrict or promote inflammation and possibly influence kidney cyst growth, Nowak said.

A necessary focus on overweight and obesity in kidney disease

Why the focus on overweight and obese individuals with ADPKD? Nowak noted that about two-thirds of people with the disease are overweight and obese. That is about the same as the general population in the United States, she said. However, being overweight and obese increases the risk of high blood pressure and Type 2 diabetes, which are major contributors to chronic kidney disease (CKD), an umbrella condition that includes ADPKD.

“As a society, as we become more sedentary and obese, it’s driving up rates of CKD, along with other diseases that go hand-in-hand with modifiable risk factors,” Nowak said.

One encouraging sign, she noted, is that the nonprofit organization KDIGO (Kidney Disease: Improving Global Outcomes) addresses weight loss in its 2025  guidelines for treating patients with ADPKD.

“Our work has somewhat had an impact globally in that these are worldwide guidelines for clinical practice and nephrology,” she said.

A personal lifestyle change to manage ADPKD

Whatever the outcome of Nowak’s study, Karen Boyd says her two years in it has changed the way she lives her life. She began the study at 248 pounds and left it at 192. Her body mass index (BMI) fell 9 points, while her cholesterol and triglyceride levels decreased. Most importantly, her kidneys did not grow.

She emphasized that the study program was not a diet, but rather a long-term lesson in how to change her lifestyle. She grew up with “clean-your plate people,” and admits to becoming sedentary over the years. The group classes, which were held weekly in the first four months of year one and monthly during year two, helped her change that. She learned about the importance of movement, mindful eating, motivation, staying hydrated, and grocery shopping for foods that maintain her kidney health, such as those lower in salt and phosphorus.

As time went on, Boyd shelved her ever-present favorites, such as cookies and baked goods, in favor of fruits, vegetables and fish. Her husband, John, joined her in cooking healthy dishes, like vegetarian soup, and in getting on the move with walks in parks around their home. They took on a notable hiking challenge with a trip to Jackson Hole, Wyoming, that included a trek along the Cascade Canyon Trail.

Boyd also has also bumped up her daily activity with yardwork and exercising while watching television. “I’m the crazy lady who parks her car on the other side of the lot and walks to the store,” she added. “I find that farthest parking spot. It’s just natural now.”

Getting healthier with a broader purpose

Now 55, Boyd is happy to improve her health and preserve her kidney function, but she has a much broader motivation. She has many family members who carry the same genetic risk for ADPKD that she does. Participating in Nowak’s study “could bring answers to my family, extended family and countless others,” she said. “Even before you know your child might have this hereditary condition, if you can set an example by keeping your blood pressure, fat levels and BMI normal, and help your kidneys, let’s do it. We need to take care of it for the next generation and slow down its progression.”

In her own way, Boyd carries forward the research undertaken by Nowak and her colleagues to address ADPKD, a frequently overlooked condition that nonetheless exacts a significant human and economic cost.

“It’s hard to have [ADPKD] because there is nothing sexy or fun about the kidneys,” Boyd said. “The CU team is interested and energetic about doing the needed work. I love them to pieces and am their biggest champion.”

As for Nowak, she is, of course, interested in finding what works to help patients like Karen Boyd, whether that be weight loss and other lifestyle changes, new drugs, or a combination of approaches. But she believes that any new therapies will require a deeper understanding of ADPKD and what drives it.

“Often what I tell patients [enrolled in trials] is we’re trying to figure out does this [ADPKD treatment] work, but we also want to know why,” Nowak said. “I think that’s the intellectual curiosity of doing research as well as trying to advance it to the next step.”

For more information about the study, contact Diana George at [email protected] or 303-724-1684.