A new study at the University of Colorado Anschutz Medical Campus takes aim at a formidable twin threat to health: chronic kidney disease and high blood pressure. For patients facing these diseases, the idea, simply put, is to take a deep breath — repeatedly.
The approach, called inspiratory muscle strength training, or IMST, is a low-tech therapy often used to help people who have difficulty breathing. An individual inhales through a hand-held device at regular intervals with maximum effort against pressure. The exercise can improve breathing by strengthening the mainstays of our respiratory system, namely the diaphragm and muscles in the ribcage.
The supposition of the current study is that high-intensity IMST could help to lower blood pressure in some people with chronic kidney disease (CKD) by dilating their arteries and improving blood flow.
Why take on both CKD and high blood pressure? They are frequent companions, said Dr. Kristen Nowak, associate professor of medicine in the Division of Renal Diseases and Hypertension at the University of Colorado School of Medicine and co-principal investigator for the study with her colleague, Dr. Michel Chonchol.
“There are more than 30 million people in the United States with CKD, and about 80% of them also have high blood pressure,” Nowak said. “In a majority of those patients, their high blood pressure is not adequately controlled.”
Breathing to combat the double threat of high blood pressure and kidney disease
Over time, high blood pressure not only increases the risk of cardiovascular disease, it can also damage kidneys, leading to or worsening CKD, Nowak added. In turn, CKD impairs the body’s ability to manage blood pressure. It’s an unhappy cycle that contributed to the more than $87 billion that Medicare paid to treat patients with CKD in 2019.
Of course, many people manage their high blood pressure with medications, Nowak said. But they often require multiple medications that produce various side effects. Aerobic exercise helps to lower blood pressure and the need for pills, but many CKD patients face barriers to getting active, including comorbidities, frailty and poor mobility, she added.
In fact, Nowak said, IMST appears to improve breathing in much the same way as aerobic exercise, while overcoming some of its limitations. She pointed to a study by study collaborators at the University of Colorado Boulder showing that IMST helped lower blood pressure in midlife and older adults who had higher than normal readings. The study also concluded that IMST boosted the function of the endothelial cells that line blood vessels and the heart, another key to regulating blood pressure.
“This intervention has actually had a pretty profound lowering of blood pressure in other populations,” Nowak said. “I thought it was an interesting [approach] that could be translated to a CKD population. We want to dilate the artery and increase blood flow with activity.”
Finding practical ways to protect the kidneys
Nowak’s overarching goal is to improve patient health in ways that burden them the least. For example, a recently published study she co-authored examined the feasibility of using calorie restriction to slow the progression of cysts in overweight and obese patients with autosomal dominant polycystic kidney disease (ADPKD), a genetic condition that frequently leads to kidney failure. Another Nowak-led trial is studying time-restricted feeding – eating only during defined windows during the day – as another possible way to manage ADPKD in people who are overweight or obese.
“I’ve always been very interested in lifestyle modifications and whether such interventions can complement or decrease the need for more medical care,” Nowak said. If evidence from the current IMST study proves effective in lowering blood pressure in CKD patients, “it’s a strategy that is cost-effective and could be easy to implement with a minimal amount of time in a patient’s home,” she added.
Blowback against high blood pressure
The five-year study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases and is recruiting men and women age 50 or older with moderate to severe CKD (stages 3 or 4) and blood pressure above 130/80. Patients who qualify get an ultrasound-aided test called flow-mediated dilation. A cuff inflates tightly to block blood flow to the brachial artery, which lies near the elbow joint. When the cuff is released, blood flows through and dilates the artery. The way the artery responds is an indication of the health of its endothelial cells. The researchers also take blood samples and biopsied endothelial cells scraped from the walls of a vein in the arm with a small wire advanced through a catheter. They will use these cells to conduct additional study research.
To set up the breathing training, Nowak and her research team measure the baseline strength of the inspiratory muscles. Participants make their maximum breathing effort against the resistance offered by the hand-held device. The study group gets “high-resistance” IMST – 75% of maximum pressure – while a control group gets “low-resistance” IMST, or 15% of maximum pressure. Both groups take 30 inhalations per day, at preset intervals, six days a week for three months.
As the study progresses, participants check in regularly for retests and to recalibrate the device based on changes in their breathing. The device stores results of the exercises, and the researchers can monitor the participants’ adherence to the regimen, Nowak said.
Putting inspiratory muscle strength training to the test
Steve Bello, a retired project manager with the City of Denver, was the first patient to enroll in the inspiratory muscle strength training study and completed it in late July. The 72-year-old Arvada resident was well into retirement in 2015 when he learned his kidney function had begun to decline. He thought dehydration and age might be to blame, but one day in late 2019, he noticed traces of blood in his urine. A nursing hot line provider, suspecting an infection, advised him to come in for a urine test, which he did.
Later that night, he saw his urine was full of blood. A CT scan showed a mass in his right kidney that turned out to be cancerous. Dr. Paul Maroni, a urologist at UCHealth University of Colorado Hospital on the Anschutz Medical Campus, removed about one-third of the kidney in January 2020. Thus far, Bello said, he is cancer-free.
“We caught the cancer in its early stages,” Bello said.
However, with the smaller kidney also came more severe CKD. Bello managed to improve his kidney function with attention to diet and exercise, but in early 2022, he noticed that his blood pressure began to creep up above 130/80, the upper end of normal. His nephrologist at UCHealth, Dr. Amber Podoll, prescribed a low-dose blood pressure medication to protect his kidneys, but Bello decided to also enroll in Nowak’s IMST trial.
“If I can stay away from meds, I like to,” he said.
Bello completed the baseline testing and went home with his hand-held device to begin IMST. The regimen called for him to inhale six consecutive times into the device, followed by a one-minute rest. He did this five times, for a total of 30 breaths, six nights a week, while watching the news. He also had regular phone visits with Nowak’s team and went into the clinic every other week to get the device recalibrated.
“I could tell the breathing was working by my sore stomach muscles,” Bello said. “But it got easier over time.”
Learning more about blood pressure control and CKD
At the conclusion of the trial, Bello repeated all the tests he’d done at baseline. He found that his blood pressure had decreased significantly and was in the healthy range. Of course, it remains to be seen why it declined. For one thing, he doesn’t know if he was in the high- or low-resistance IMST group. He’s also improved his kidney function by paying attention to his diet and walking nine holes when he golfs to get more exercise. These steps to manage his CKD may also have dropped his blood pressure.
It will be several years before Nowak can draw any conclusions from her study. But if high-resistance IMST proves effective in lowering blood pressure in people with CKD, she also wants to know why. Her trial includes “innovative translational assessments” aimed at understanding the changes that occur “mechanistically” with IMST.
For example, the research team will take the biopsied endothelial cells from participants and analyze them to see if they have changed after IMST – and if so, how those changes might have contributed to improvements in blood pressure levels. They will also study changes in nitric oxide production – which also plays a key role in dilating arteries – as well as blood flow to the kidneys and to the substances that control the body’s metabolism.
As for Steve Bello, he said he welcomes the opportunity to contribute to the research of Nowak and others. Volunteering for studies, he said, allows him to get regular testing that he wouldn’t otherwise have access to and helps him “stay on track” with his health. Beyond that, he hopes his medical information can assist in advancing patient care.
“I feel good about trying to help the industry,” Bello said. “If I can be in something that will help me and other people, I’m all for it.”
For more information about the study contact Mallory Britz, 303-724-7795, or [email protected].