{"id":20406,"date":"2019-01-23T16:16:25","date_gmt":"2019-01-23T23:16:25","guid":{"rendered":"https:\/\/www.uchealth.org\/today\/?p=20406"},"modified":"2023-05-30T09:03:08","modified_gmt":"2023-05-30T15:03:08","slug":"study-looks-at-weight-loss-to-manage-dangerous-hereditary-kidney-disease","status":"publish","type":"post","link":"https:\/\/www.uchealth.org\/today\/study-looks-at-weight-loss-to-manage-dangerous-hereditary-kidney-disease\/","title":{"rendered":"Study looks at weight loss to manage dangerous hereditary kidney disease"},"content":{"rendered":"
<\/div>

Mary Johnston-Clark calmly received the news that her kidneys were dotted with cysts. She\u2019d seen it coming.<\/p>\n

\"A
The trial examines if calorie restriction and fasting can slow the progression of polycystic kidney disease in overweight and obese patients. Photo: Getty Images.<\/figcaption><\/figure>\n

Then 40, Johnston-Clark was at Northwestern University near Chicago for periodic tests she\u2019d completed for nearly two decades as part of the CARDIA trial, a long-term study of coronary artery risk.\u00a0 A torso scan revealed the kidney cysts.<\/p>\n

\u201cI said, \u2018That would make sense,\u2019\u201d Johnston-Clark recalled 18 years later as she sat in a tiny exam room in the CU Medicine building<\/a> on the\u00a0 Anschutz Medical Campus. \u201cIt wasn\u2019t a real shock, given my family history.\u201d<\/p>\n

The cysts remain, the product of a genetic disease called autosomal dominant polycystic kidney disease (ADPKD). The disease produces fluid-filled sacs that gradually crowd, enlarge and weaken the kidneys and can lead to renal failure. It had been passed on to Johnston-Clark by her father and to him by his father. She knew she had a 50-50 chance of having it herself.<\/p>\n

\u201cI was like, \u2018Damn it, I thought I might have missed that bullet,\u2019\u201d Johnston-Clark said.<\/p>\n

Silent progression<\/strong><\/p>\n

\"\"
Mary Johnston-Clark of Lander, Wyoming, hopes her participation in a trial on the UCHealth Anschutz Medical Campus will help her not only lose weight but also manage her hereditary polycystic kidney disease. Photo courtesy Mary Johnston-Clark.<\/figcaption><\/figure>\n

It\u2019s not surprising that she hadn\u2019t wasted much energy worrying about it. There is no cure for ADPKD and only one FDA-approved treatment that is reserved for those whose disease is progressing rapidly, said Dr. Kristen Nowak<\/a>, assistant professor of medicine with the University of Colorado School of Medicine. Johnston-Clark hadn\u2019t experienced any pain or other overt symptoms at the time of her diagnosis \u2013 also not unusual, Nowak said.<\/p>\n

\u201cPatients with ADPKD can be totally asymptomatic,\u201d she said. Many people with the disease don\u2019t have decreased kidney function until they are around age 50, she added.<\/p>\n

There are signs that may point to ADPKD, including hypertension, flank pain and blood in the urine \u2013 a signal of cysts rupturing \u2013 Nowak said. \u201cMonitoring blood pressure is especially important, especially if we\u2019re seeing it in kids with a family history of [the disease],\u201d she noted.<\/p>\n

Now Nowak is also focused on understanding the role that overweight and obesity could play in the progression of PKD.<\/p>\n

Weighing treatment options<\/strong><\/p>\n

She\u2019s leading a small trial<\/a> funded by the Colorado Clinical and Translational Sciences Institute<\/a> and the National Institutes of Health exploring the feasibility of using two dietary programs \u2013 daily caloric restriction and intermittent fasting \u2013 to potentially slow cyst growth in patients with ADPKD.\u00a0 The caloric restriction group cuts their calories by approximately 34 percent, based on their resting metabolic rate, Nowak said. Those in the intermittent fasting group restrict their calories to about 20 percent of their overall needs three days a week; on the other days, they have no restrictions and don\u2019t have to count calories.<\/p>\n

Both groups receive instruction from registered dietitians with the Anschutz Health and Wellness Center<\/a> and interact with one another through remote videoconferencing. Participants also keep track of their diet and weight through smartphone apps and wireless scales. They meet once a week for the first 13 weeks of the study, then will meet once a month for the remaining nine months.<\/p>\n

\"\"
Dr. Kristen Nowak leads the pilot of a study that examines the feasibility of using weight-loss programs to manage hereditary polycystic kidney disease in overweight and obese individuals. Photo by UCHealth.<\/figcaption><\/figure>\n

Nowak is collaborating with Dr. Vicki Catenacci<\/a>, a UCHealth endocrinologist who is leading a trial that uses a similar approach with otherwise healthy patients who are overweight or obese. Catenacci developed a curriculum that covers topics that include calorie counting, exercise, portion control and the like.<\/p>\n

It\u2019s only a first step: a proof-of-concept to demonstrate whether or not patients can adhere to the program, Nowak said. But patients will also get MRIs to measure their kidney volumes at baseline and at the conclusion of the study to gauge the rate of cyst growth.<\/p>\n

\u201cHopefully we will see a trend to improvement,\u201d the key to taking the study to the next phase, Nowak said.<\/p>\n

Intersecting questions<\/strong><\/p>\n

Why investigate weight loss as a possible technique for managing ADPKD? Nowak\u2019s background is in physiology, which sparked an interest in how diet and exercise changes could affect aging in healthy adults. She went on to post-doctoral work in nephrology<\/a>, developing an interest in how the kidneys interact with the blood vessels of the body.<\/p>\n

That introduced her for the first time to ADPKD, a condition she thought was ripe for study because it involves genetics \u2013 opening the potential population of subjects to both children and adults \u2013 and lifestyle factors that might be modified to reduce risks like high blood pressure and cardiovascular disease that are common in all kidney disease.<\/p>\n

As part of a Career Development Award from the NIH, Nowak led a study<\/a>\u00a0 that began in 2015 and is expected to run to 2020 that examines the effectiveness of curcumin \u2013 a natural substance found in the spice turmeric, a staple of curry powder \u2013 in improving the health of blood vessels and putting the brakes on kidney growth in both children and adults with ADPKD.<\/p>\n

\u201cI wanted to try to tease out the effects of genetic contributors to the disease versus lifestyle,\u201d Nowak said.<\/p>\n

Nowak also co-authored a February 2018 article<\/a> published <\/u>in the Journal of the American Society of Nephrology <\/em>that reviewed more than 400 patients with ADPKD enrolled in the Halt Progression of Polycystic Kidney Disease Study, which looked at methods of controlling blood pressure. After categorizing the patients\u2019 body mass index and evaluating their kidney growth over a five-year period, Nowak and her colleagues concluded that overweight and obesity were strong predictors of more rapid progression of ADPKD.<\/p>\n

The impetus for the current trial came after Nowak read of studies conducted on rodents that found that restricting the animals\u2019 calorie intake slowed their ADPKD: they developed fewer cysts and the kidneys grew at a slower rate than subjects without calorie restrictions. The studies found overlap in cell-signaling pathways in overweight and obese rats and pathways that promote the growth of kidney cysts, Nowak said.<\/p>\n

\u201cI thought that maybe periods of fasting in humans could have a benefit in the progression of the disease,\u201d she said.<\/p>\n

Experience tips the scales<\/strong><\/p>\n

Johnston-Clark admits that she\u2019s \u201cnever really done the diet thing,\u201d thinking that she could take the weight off by herself. But she had a scare in the spring of 2017 after a urinary tract infection spread to one of the cysts in her kidneys. Providers at the hospital in Lander, Wyoming, where she lives with her husband, couldn\u2019t get the infection under control and Johnston-Clark began getting septic, prompting calls to air-lift her to a critical-care facility.<\/p>\n

She woozily told them to first call her nephrologist at UCHealth University of Colorado Hospital, Dr. Michel Chonchol<\/a>, who calmly advised administering ciprofloxacin, an antibiotic proven effective in knocking out renal cyst infections. Johnston-Clark recovered and left the hospital 10 pounds lighter and with her blood pressure lower.<\/p>\n

The experience sent a powerful message. Johnston-Clark enrolled in a multisite study Chonchol leads at CU<\/a> of the lung cancer drug tesevatinib, which has shown promise in controlling kidney growth in patients with ADPKD. He also \u201cquietly and firmly\u201d suggested that she try to get her weight under control to reduce the strain on her kidneys.<\/p>\n

\u201cClearly I was not able to do it on my own,\u201d Johnston-Clark said. \u201cKnowing what I\u2019m supposed to do with my diet wasn\u2019t enough. I needed the structure.\u201d<\/p>\n

Taking control <\/strong><\/p>\n

She enrolled in Nowak\u2019s study two months ago, joining the caloric restriction group. Her resting metabolic rate established her calorie limit. She makes her own food choices based on that number and recommendations made during the weekly videoconference meetings led by registered dietitian Marsha Miller<\/a> at the Anschutz Health and Wellness Center that cover topics in Catenacci\u2019s curriculum.<\/p>\n

\u201cThat\u2019s very important to me,\u201d Johnston-Clark said, \u201cbecause after the study is done you\u2019re supposed to continue [with the program], and it\u2019s something I want to continue. I\u2019m developing habits that are important to my future health, not just a study.\u201d<\/p>\n

She uses the MyFitnessPal app on her phone to track what she eats and balance her meals \u2013 splurging a bit for one meal is okay as long as she makes up for it the other times she eats.<\/p>\n

\u201cYou can eat anything you want,\u201d Johnston-Clark said. You just need to be aware of how that fits into your balanced diet. That\u2019s the key.\u201d<\/p>\n

Nowak\u2019s goal, of course, is to figure out if people with ADPKD will adhere to this type of program. Johnston-Clark offers encouraging words on that score.<\/p>\n

\u201cIt seems like a feasible approach,\u201d she said. \u201cAdding awareness of what I eat makes me feel more in control, not less.\u201d Since starting the study, she\u2019s dropped from 265 pounds to just under 259, and her resting heart rate has decreased. Her creatinine levels, a key measure of kidney function, have continued a decline that she said began about a year ago.<\/p>\n

Long-term benefits<\/strong><\/p>\n

If Nowak\u2019s hypothesis plays out, helping patients with ADPKD manage their weight and blood pressure could have a profound effect on their lives and help to manage soaring health care costs.<\/p>\n

\u201cThat\u2019s particularly important for a disease like ADPKD because it is lifelong,\u201d Nowak said. \u201cAny drug that is developed would likely have to be taken long-term, which is difficult for people. Whether as a stand-alone therapy or in conjunction with new treatments, lifestyle-related changes can have a major impact on people\u2019s lives \u2013 beyond cutting health care costs.\u201d<\/p>\n

The potential benefits are even greater if providers diagnose ADPKD early and encourage healthy lifestyle changes in kids, Nowak concluded.<\/p>\n

\u201cIf we could take the pediatric population, keep them at an ideal weight and prevent weight gain as they start to get older, maybe that improves the trajectory of the disease as well \u2013 if you can educate them that this is important.\u201d<\/p>\n

For more information on the study, contact Dr. Kristen Nowak at <\/em>kristen.nowak@ucdenver.edu<\/em><\/a> or Beverly Farmer at <\/em>Beverly.farmer@ucdenver.edu<\/em><\/a> (303-724-7790<\/span>).<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Mary Johnston-Clark calmly received the news that her kidneys were dotted with cysts. She\u2019d seen it coming. Then 40, Johnston-Clark was at Northwestern University near Chicago for periodic tests she\u2019d completed for nearly two decades as part of the CARDIA trial, a long-term study of coronary artery risk.\u00a0 A torso scan revealed the kidney cysts. 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