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Kidney Patients: Protecting Your Heart!


Many of us may not be aware of this, but research shows a link between kidney disease and cardiovascular problems. In fact, of the 20 million Americans diagnosed with kidney disease, more than half will die from heart disease. Now, researchers are testing a new therapy that would help protect a kidney patient's heart.

Sixty-six year-old David MacKenzie gets a workout most days, even if it's just a quick, brisk walk. He's tried to maintain a healthy lifestyle for most of his adult life.

MacKenzie told Ivanhoe, "Early on, probably in my mid to late 30s, I began to have elevated blood pressure."

David didn't know it growing up, but he and one of his sisters would also develop polycystic kidney disease, an inherited condition that affects kidney function.

Jeanie Park, MD, MS, Assistant Professor at Emory University School of Medicine in Atlanta explained, "Even though it's adaptive to have this fight or flight response in the situation when you need it, if it's revved up all the time, then it's not good for your body."

Dr. Park found that a drug already FDA-approved for a metabolic disorder, dials down the adrenaline levels in kidney patients. It's called tetrahydrobiopterin.

Dr. Park studied 32 men with moderate kidney disease, and found a decrease in sympathetic nerve activity in those who took the drug for 12 weeks.

Dr. Park said, "It could be a novel way of reducing cardiovascular risk and potentially reducing blood pressure in patients with hypertension or chronic kidney disease."

For patients like David MacKenzie, that would mean managing just one chronic condition, kidney disease, instead of two.

Right now doctors use beta blockers and another drug, clonidine, to treat high blood pressure and the over-activation in the sympathetic nervous system. Dr. Park says those drugs are often hard for patients to tolerate.

Contributors to this news report include: Cyndy McGrath, Supervising Producer/Field Producer; Cortni Spearman, Assistant Producer and Jamison Koczan, Editor.

 

Background: The main purpose of the kidneys is to filter waste and excess fluids from your blood. When a disease or condition impairs kidney function, damage to the kidneys can occur, causing chronic kidney disease. Chronic kidney disease or chronic kidney failure describes the gradual loss of kidney function. Polycystic kidney disease ,or PKD, which is what David MacKenzie has, is an inherited disorder where clusters of cysts develop within the kidneys. These cysts can grow to be very large and also can develop in your liver and elsewhere in your body and can cause an array of serious complications. Some include high blood pressure, headaches, back pain and even kidney failure.

 

CAUSES OF CHRONIC KIDNEY DISEASE: Diseases and conditions that commonly cause chronic kidney disease include:

·     Type 1 or type 2 diabetes

·     High blood pressure

·     Polycystic kidney disease

·     Glomerulonephritis (an inflammation of the kidney's filtering units)

·     Interstitial nephritis (an inflammation of the kidney's tubules and surrounding structures)

·     Prolonged obstruction of the urinary tract

·     Vesicoureteral reflux (a condition that causes urine to back up into your kidneys

·     Recurrent kidney infection

HEART PROBLEMS AND KIDNEY DISEASE: Jeanie Park, MD, MS, Assistant Professor at Emory University School of Medicine in Atlanta, Georgia says that people with kidney disease have high adrenaline levels, high sympathetic nerve levels, increased heart rate and increased blood pressure. She also says that this leads to "An increased cardiovascular risk in these patients." Dr. Park is conducting a clinical trial of the drug tetrahydrobiopterin to see if it could help with this problem.

 

FOR MORE INFORMATION ON THIS REPORT, PLEASE CONTACT:

Quinn Eastman

Emory Health Sciences Communications

404-727-7829

qeastma@emory.edu

 

If this story or any other Ivanhoe story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Marjorie Bekaert Thomas at mthomas@ivanhoe.com

 

Jeanie Park, M.D., M.S., Assistant Professor of Medicine at Emory University School of Medicine discusses a new drug that could help slow the progression of chronic kidney disease.  

 

Interview conducted by Ivanhoe Broadcast News in March 2015.

Tell me about the impact on kidneys when you're taking drugs. 

Dr. Park: Chronic kidney disease is actually very common in the United States. There are more than 20 million people with kidney disease who don't even know they have chronic kidney disease. The two most common causes of chronic kidney disease are diabetes and hypertension. There are some other causes of kidney disease that can be linked to medications.  Some prescription and non-prescription medications can have negative effects on the kidney.  For example, some very common medications that people take for aches and pains, like nonsteroidal anti-inflammatory drugs, or NSAIDS, can sometimes lead to chronic kidney disease.  If you already have kidney disease, it is very important to avoid medications that can further worsen kidney function and not take any medications without a physician's approval.

What's the danger if you don't even know you have chronic kidney disease?  

Dr. Park: The earlier we can catch chronic kidney disease, the more likely it is that we can treat it and prevent the progression of kidney disease.  Chronic kidney disease usually does not present with symptoms.  It's kind of like hypertension in that way. High blood pressure is also not symptomatic. Oftentimes you don't know you have high blood pressure unless you go to the doctor and get your blood pressure checked, or that you have kidney disease unless you get blood work and urine studies checked by your doctor.  It is important to have regular check-ups by your physician since early diagnosis and treatment improves outcomes.    

Can you tell me about the drug that you're studying?

Dr. Park: The drug itself is called sapropterin dihydrochloride, which is 6RBH4. That's the synthetic form of tetrahydrobiopterin. Tetrahydrobiopterin is actually an endogenous factor that's in our bodies. It acts as an essential co-factor for an enzyme which acts to increase levels of nitric oxide in the body. 

What does the nitric oxide do?  

Dr. Park: Nitric oxide is thought to have a lot of beneficial effects in the body. It's a vasodilator, meaning it makes your blood vessels relax. It has a positive effect on blood pressure. It turns out that it has other effects as well in the central nervous system. In this study in particular, we looked at how tetrahydrobiopterin, or the synthetic form 6RBH4, affects sympathetic nerve activity or adrenaline levels in patients with kidney disease. 

Why would that be important when you are looking at adrenaline levels?

Dr. Park: It's important to recognize if you have chronic kidney disease because you're at a much higher risk of developing cardiovascular disease. This is independent of all other risk factors. There are a lot of different reasons that are thought to cause this increased risk of cardiovascular disease in patients with kidney disease. One of them is a chronic elevation in sympathetic nervous system activity, more commonly thought of as the fight or flight system, the end result of which increases adrenaline levels in your body. We and other groups have shown that people with kidney disease have high adrenaline levels, or high sympathetic activity at baseline. That's one of the factors that leads to increased cardiovascular risk in these patients. 

Could you describe what it would be like for your system?

Dr. Park: Patients aren't going to necessarily feel like they're in a fight or flight situation. What adrenaline does is increase your heart rate and increase your blood pressure. Norepinephrine works on the blood vessels and causes constriction, which then causes an increase in blood pressure. It has also been shown to increase the rate at which your kidney disease progresses. It also has adverse effects on the heart and the blood vessels that are independent of blood pressure. Even though it's adaptive to have this fight or flight response in the situation when you need it, if it's revved up all the time, then it's not good for your body and it ends up causing increased risk to the heart. 

In addition to the increased risk to the heart, did you say it can also hurt the kidneys and progress?   

Dr. Park: Yes. There's a lot of newer literature that shows this high sympathetic tone to the kidneys is associated with faster progression of kidney fibrosis and deterioration of kidney function. 

Is there no treatment for kidney disease?

Dr. Park: The specific treatment for kidney disease depends on the cause.  If the disease is due to diabetes or high blood pressure, we control blood sugar and control the blood pressure.  We stop medications that can hurt the kidneys such as NSAIDs.  If there is protein in the urine, we use Ace inhibitors, or angiotensin receptor blockers to try to decrease protein in the urine. If the kidney disease is due to other causes such as infections, or autoimmune disease, we treat the underlying disease, and will sometimes use immunosuppressive medications. In every case of kidney disease, it is important to treat high blood pressure, blood sugars, and proteinuria.  

If the kidney disease progresses to a certain point, can this be life-threatening and you look at transplant?

Dr. Park: Yes. In general, although not always, chronic kidney disease is a progressive disease. When you reach stage 5, some kidney disease patients start to feel symptomatic or have a decline in health and need to go on some type of renal replacement therapy, such as kidney transplant or dialysis. 

What is your hope with looking at this drug? 

Dr. Park: Our goal is to try to come up with novel treatments with fewer side effects that can impact this increased risk of cardiovascular disease that our patients with chronic kidney disease have. There are 20 million people with chronic kidney disease, but much fewer with end-stage renal disease. That's because many of them die from cardiovascular disease before they even reach end-stage renal disease. Our goal is to try to catch them before that happens and try to modify their risk prior to any cardiovascular event happening. 

If there was one take away you would want viewers to know about the research you're doing, what would it be?

Dr. Park: We've made a lot of advances in terms of our ability to treat blood pressure and kidney disease.  However, there is still a lot we don't know about the pathogenesis of kidney disease and the associated cardiovascular risk, and the best way to intervene on these conditions.  Research, both at the basic level in the laboratory as well as clinical trials, is vital for improving outcomes in our patients. In doing so, we can impact this huge public health problem of chronic kidney disease and the associated cardiovascular outcomes. 

Is this drug something that is in clinical trials right now?

Dr. Park: This drug is FDA approved for a completely different indication. It turns out that this drug is a co-factor for phenylalanine hydroxylase, which is another enzyme that can affect certain forms of phenylketonuria. It turns out that for our purposes, it acts as a co-factor for another enzyme, which is nitric oxide synthase. We're the first to look at this in patients with kidney disease. My colleague has looked at this in patients with hypertension as well, but there haven't been any larger randomized control trials yet. This drug could essentially be a novel way of reducing cardiovascular risk and potentially reducing blood pressure in patients with hypertension or chronic kidney disease. 

What are some symptoms that somebody might have that would make them want to go and get checked for kidney problems?  

Dr. Park: Usually, you're pretty far along before you have any symptoms. Early to moderate kidney disease is usually without symptoms.  Some patients might present with swelling in the legs or higher blood pressure, and with more advanced disease can have nausea, decreased appetite, weight loss, confusion.  It's really important to be screened for risk factors like diabetes and high blood pressure. You need to see your primary care physician regularly and have blood pressure and laboratory screenings. If you're a diabetic, we routinely screen the urine to make sure you don't have protein in the urine. Catching kidney disease early is very important to give adequate treatment.  

Is there a length of time that you're looking to study this drug and what would be the next step? 

Dr. Park: This was actually a small randomized control trial and we are finished. We're going to look at other interventions that can affect sympathetic tone that are relatively safe without side effects. One of them is exercise therapy with a combination of tetrahydrobiopterin. We'll study blood pressure and sympathetic activity as well as exercise capacity in these patients.