Monthly Archives: May 2013

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Using the enzyme mix in Xiaflex to treat Dupuytren’s contracture, frozen shoulders and now cellulite

It’s a nuisance during the summer months, when the weather heats up and bathing suits and shorts come out. Never a distinguishing or welcome sign, it’s the dimpled skin condition known as cellulite.

Researchers at Stony Brook University, however, believe they have come up with a possible injection-based cure. Using the same enzymes they’ve applied with frozen shoulder and Dupuytren’s contracture, a deforming hand condition that limits finger mobility, Marie Badalamente and Alexander Dagum have had some success in treating 10 patients in a first-round study of their injections.

Later this year, they expect to enter the Food and Drug Administration’s so-called Phase 2A trials, where they will continue to test their drug, called Xiaflex. They plan to advertise for study subjects and will likely test their remedy against a placebo (using something harmless as an injection that isn’t known to have any effect on cellulite).

In their first trial, their results showed promise. On average, patients saw a 77 percent reduction in cellulite one day after the injection. After six months, those patients still saw a 76 percent reduction. Side effects included soreness, black-and-blue areas and mild edema.

“This is the first properly controlled clinical trial of an injectable treatment that has a good chance to be FDA-approved,” said Badalamente in an interview.

Cellulite affects about 90 percent of women and 10 percent of men. Women have “more of these thin-strand fibers” in their thighs and buttocks, so the fat “kind of pushes up and through, although like a honeycomb of fibers,” said Badalamente, who is a professor of orthopedics. The result is this classic dimpling appearance in those areas.

“Patients flock to cosmetic plastic surgeons’ offices in search of treatments that may help them,” she said. “It’s very troubling to a women’s sense of herself.”

In a press release, Dr. Dagum, who is the interim chairman of surgery at Stony Brook School of Medicine, added that the “methods to remove cellulite are many, but none yet have been supported in medical literature to be effective or potentially usable as a standard practice.”

Through her work with other problems, like Dupuytren’s contracture and frozen shoulder, Badalamente had used the enzyme mixture in Xiaflex. Badalamente and Edward Wang, an associate professor of Orthopedics, are collaborating on the frozen shoulder treatments.

“The common thread is the presence of a substance called collagen,” Badalamente said. “In Dupuytren’s contracture, there’s an abnormal deposition [of collagen] from the palm to the fingers. There’s a normal collagen capsule around the shoulder. In frozen shoulder, there’s an adhesion of collagen that builds up.”

The enzyme mixture lyses, or dissolves, the collagen in frozen shoulder, freeing the shoulder to return to its normal range of motion. For frozen shoulder, these Phase 2A trials have just been completed. The treatment reduces the need for extended physical therapy or arthroscopy (surgery). Phase 2B trials will begin this summer or fall.

“It was readily apparent to me that this injectable drug, which is a combination of two collagenase enzymes, clearly had other uses in a class of disorders,” she explained. “The light bulb on the top of the head moment was that I knew about the microanatomy of cellulite.”

Although the studies with Xiaflex on cellulite are still in the early stages, the use of the enzyme mixture to treat Dupuytren’s contracture has been effective over a longer period of time. If, for example, it recurs years later, patients can get another injection.

“That might be the same for cellulite,” Badalamente said.

The researchers cautioned that safety always comes first in any new treatment, even with a procedure that has won FDA approval for other uses.

For the Dupuytren’s contracture, the process took about 15 years.

“That one probably took too long,” Badalamente said. “Each indication, as it comes forward, should take much less time.”

Badalamente said she sees firsthand the problems that affect patients.

“In the case of the hand, if you can image this disease affecting both of your hands, [there’s] misery,” she said. “It’s not cancer and it’s not going to kill you, but it’s gong to interfere with your function. If you see that misery and you’re able to potentially think about a therapy that’s less invasive than surgery, there’s nothing better in the world than getting a ‘Thank you’ from the patients.”

The male ensemble of Wood, Evan Teich, Josh Rothberg, Ben Rosenbach, Matthew Michael Urinak, Dennis Setteducati and Paul Velutis along with the females Jamila Sabares-Klemm, Diana Rose Becker, Audra Rizzo, Erin Raquel Garcia and Kate Cherichello all meshed together like the breech of a 16-inch battleship’s gun — another tribute to DiPietropolo.

This season-topper was yet again another exhibition of what the Engeman can mount in its unquestionable adherence to the highest norms of professionalism.

“South Pacific” will run at the Engeman Theater, 250 Main St., Northport through July 14. Call 261-2900 or go to www.engemantheater.com for tickets.

 

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Finding an inexpensive catalyst to break water down to its components is the key

It often looks like an outline of Mickey Mouse’s head, with a large circle and two overlapping or attached smaller circles. Drawn in a chemistry class, the larger circle is oxygen, while the two smaller ears are hydrogen.

In plants that produce their own food through photosynthesis, taking apart the three circles helps them make food, such as sugars. Scientists like Wei-Fu Chen at Brookhaven National Laboratory are imitating nature by breaking apart, or electrolyzing, water, releasing hydrogen that could serve as an alternative to fossil fuels.

“This process mimics how plants convert sunlight and nutrients into sugars,” said Chen.

As the lightest element, hydrogen has the highest gravimetric energy density of any known fuel, which means it produces the highest energy of all the elements.

Scientists can reduce the effort it takes to split water by using a catalyst. While platinum and palladium have fulfilled that role, they are expensive, which makes them less viable long-term options.

Chen suggested twin high school students Shilpa and Shweta Iyer from Comsewogue High School, who were working in his lab, go home and search their kitchen for ingredients that, using much more cost-efficient substances like metal carbide and metal nitride, might become a catalyst alternative. In the presence of molybdenum, soybeans, which are rich in proteins, worked. The 17-year-old Iyer twins recently placed fourth in the chemistry category of the Intel International Science and Engineering Fair for their efforts (see related story in the Port Times Record and online).

So far, in tests with soybeans, the catalyst has continued to be effective for over 500 hours. The production process, Chen said, is mature for industrial applications, with a projected cost that is “fairly economical” compared to other options. For commercial use, however, tests may need to take at least a year. Chen is searching for collaborators and would like to transfer the technology to an interested commercial partner.

Now that his lab has developed a process that works, Chen said that the next steps involve understanding the chemical mechanism that enables soybeans to act as a catalyst in the electrolysis of water.

“We don’t know why it’s so active,” he explained. “My job is to figure out the mechanism in the solution.”

Chen is able to tap into the considerable resources at BNL, including the National Synchrotron Light Source. By shooting beams of light through the reaction, Chen has found information about the catalytic active center and how the applied voltage changes its electronic state. He plans to study how changes in some of the conditions, such as the temperature or the pH (whether the solution is more of an acid or a base) affect the process.

The NSLS beams can allow scientists to monitor changes that occur in an incredibly short time scale, which makes it possible to track small changes in the reaction.

“By knowing the reaction mechanisms, scientists will be able to predict new effective structures for the water electrolysis and may find new principles in the reaction,” Chen suggested.

Chen explained that developing a hydrogen fuel-based economy remains a challenging task. While he is working hard to develop ways to make hydrogen fuel more available through water electrolysis, other scientists are researching the problem of storing and transporting hydrogen.

“The coming hydrogen age will be based on the completion of production, delivery, storage and utilization,” Chen said.

Chen said some hydrogen-driven cars are already available for purchase.

“There are already some prototype products out there, but the problem is that the cost is too high,” he said. There are fuel cell cars that use hydrogen in California.

Chen lives in Ridge with his wife Chiu-Hui Wang (who uses the American name Chloe). Wang works as an electron microscope specialist in the chemistry department at BNL and at Graphene Laboratories in Calverton.

A native of Kaohsiung City, the second largest city in Taiwan, Chen said he enjoys the natural life and the fresh air on Long Island. He also loves skiing, hiking and photography. He has a blogspot site where he has posted pictures of a fawn foraging in the snow and a negative photo of rainwater on a window. Photography inspired him in 2006, when he viewed a series of photographs of Taipei City in 1957 taken by a member of the U.S. Army, Tom Jones.

As for his work, Chen hopes hydrogen fuel becomes a viable, and affordable, alternative to fossil fuels.

“Considerable work needs to be done before a hydrogen-fueled vehicle becomes an option for us,” he said.

 

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The ‘normal’ pulse range may help impact longevity

Everyone has a heart rate, so everyone needs to pay attention. But what does that heart rate, or pulse, tell us beyond the obvious fact that we are alive?

Our “normal” resting heart rate is between 60 to 100 beats per minute. We know that a RHR above 100 bpm is abnormal; it is referred to as tachycardia, or a racing heartbeat, and has potentially serious consequences. However, even “normal” RHRs can be stratified to identify risks for diseases. What I mean is that, even in the “normal” range, as your resting heart rate increases, so do your potential risks. Actually, RHR below approximately 70 bpm may be ideal.

The importance of the resting heart rate should not be underestimated. In fact, it may play a role in longevity, heart disease — including heart failure, arrhythmias, heart attacks and sudden cardiac death, and even chronic kidney disease.

The good news is that the RHR is modifiable. Methods that may reduce your rate include medications for high blood pressure, such as beta blockers and lifestyle modifications, including meditation, dietary changes and exercise.

 

Impact on lifespan

We all want to live longer and healthier lives. Reducing the RHR may be an important component in achieving this goal.

In the Copenhagen Male Study, a prospective (forward-looking) study that followed 2,798 participants for 16 years, results showed that those with higher resting heart rates had greater risk of death (Heart Journal 2013 Jun;99(12):882-7). There was a linear relationship between risk of death and increasing RHR. Those who had a resting heart rate above 90 bpm were at a threefold greater risk of death, compared to those who had a RHR at or below 50 bpm. RHR was inversely related to the amount of physical activity.

Thus, the authors concluded that a “healthy” person with higher RHR may still have a shorter lifespan, with all other factors being equal, such as physical activity and blood pressure.

In contrast with the previous study, the following one took a “glass is half-full approach” to longevity. The Jerusalem longitudinal cohort study showed that elderly women and men who had a lower RHR lived the longest (J Am Geriatr Soc. 2013;61(1):40-45). There were more than 2,000 participants, ranging from 70 to 90 years old.

 

Heart disease mortality

In the Nord-Trondelag health study, a prospective observational study, those with a higher RHR at the end of the study than they did 10 years prior, at the beginning of the study, were more likely to die from heart disease (JAMA 2011; 306:2579-2587). In other words as the RHR increased from less than 70 bpm to over 85 bpm, there was a 90 percent greater risk of heart disease, compared to those who maintained a RHR of less than 70 throughout the two measurements. This study involved 30,000 participants, but unlike some other studies, many of us can relate to the population: They were at least 20 years old and were healthy volunteers.

Heart attacks

It is more common for women to have heart attacks with atypical symptoms than men. Therefore, it is very important for women to reduce their risks. In the Women’s Health Initiative, results showed a 26 percent decrease in the risk of cardiovascular events in those postmenopausal who had a RHR below 62 bpm, compared to those who had a RHR above 76 bpm (BMJ. 2009 Feb 3;338:b219). Interestingly, these results were even more substantial in the subgroup of women who were newly postmenopausal, ranging in age from 50 to 64.

 

Effect on kidney function

Since I wrote about chronic kidney disease on May 9, I thought an interesting follow-up might be resting heart rate and its impact on kidney function. In the Atherosclerosis Risk in Communities Study, results showed that the most severe form of chronic kidney disease, end-stage renal disease, was 98 percent more likely to occur in those with the highest RHR, compared to those with the lowest (J Am Soc Nephrol. 2010 Sep;21(9):1560-70). There were approximately 13,000 participants in the study, with a 16-year follow-up.

The authors hypothesized that this negative affect on the kidney may be due to a loss of homeostasis in the autonomic (involuntary) nervous system, resulting blood vessel dysfunction, such as increased inflammation and vasoconstriction (narrowing).

 

Eating fish

What can be done to reduce the resting heart rate with minimal side effects? Fish consumption has recently been shown to have a positive effect. In a study, European men who ate greater amounts of fish — more than one serving per week — had lower resting heart rates than those who ate fish rarely (Circulation. 2003;108:820-825). There was also a direct relationship between the amount of fish consumed and the RHR: The more fish consumed per week, the greater the reduction in RHR. This was a prospective observational study involving about 5,000 men. Some beneficial side effects of eating fish included decreased triglycerides and diastolic (lower number) blood pressure, as well as increased HDL (“good cholesterol”). Even after controlling for these beneficial side effects, there still was a significant improvement in RHR with fish consumption.

Is there a resting heart rate that is too low? Well, it depends on the context. If you are a marathoner or an athlete, then a RHR in the 40s may not be abnormal. For a healthy, physically active individual, it is not uncommon to have a resting heart rate in the 50s. However, if you are on medications that reduce your RHR and/or have a chronic disease, such as heart failure, it is probably not advisable to go much below 60 bpm. Always ask your doctor about the appropriate resting heart rate for your particular situation.

Thus, resting heart rate is an easy and inexpensive biomarker to potentially determine risk stratification for disease manifestation and to increase longevity, even for those in the “normal” range. We can utilize RHR as tool for primary prevention of disease. The fact that it is modifiable means it is something that we need to monitor, so that we can achieve the ideal RHR, rather than just the “normal.”

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

New dog park will be off Boyle Road

Irene Rabinowitz with her dog, Sydney, at the site of the future dog park in Selden. Photo by Erika Karp

Soon Middle Country dogs and their owners won’t have to travel far for puppy play dates or a walk in the park, as plans for a local dog park are moving forward.

The park, which will be located on a property off Boyle Road, just north of Independence Plaza in Selden and across from Washington Heights Street, could be completed by the end of this year, according to Councilwoman Kathy Walsh (I-Centereach).

Irene Rabinowitz, a Selden resident and the former owner of Barks-n-Bubbles Boutique on Middle Country Road in Centereach, has been a driving force behind the project. In 2011, Rabinowitz created Central Suffolk Paws, a local affiliate of Long Island Dog Owners Group, a nonprofit organization dedicated to increasing access to parkland for dogs and their owners.

“You go into this wooded property right off of Boyle Road [and] it’s just so relaxing and peaceful,” Rabinowitz said in a phone interview about the planned site for the dog park.

Walsh said in a phone interview there is money available in this year’s town budget to create a small gravel parking lot and to install fencing for the park, but she was unsure of the project’s total cost. The park will take up about four acres on the northern side of the 10-acre wooded property. Paths that already exist throughout that section will remain for dogs and their owners to roam freely.

Rabinowitz, who owns four dogs including an 11-year-old Australian shepherd named Sydney who needs to stay active, said she has always wondered why there were no dog parks in the central Suffolk area. Last October, Rabinowitz and Sydney completed a 70-mile walk from Centereach to Montauk to raise money and awareness for Central Suffolk Paws and the Arthritis Foundation, Long Island Chapter.

“It is a matter of socialization,” Rabinowitz said about the need for dog parks. “[Sydney] wants to be out there with other dogs and people.”

Brookhaven Town has a few parks for dogs already, including the town’s Middle Island Dog Park, one in Mud Creek County Park in Patchogue and another at the county’s Robinson Duck Farm in Brookhaven hamlet. There are also other dog parks throughout Suffolk County, including the Blydenburgh Dog Park in Hauppauge and East Northport Dog Park in East Northport.

All of these are 20 to 30 minutes away from this community so that’s why we need one here,” said Kevin McCormack, the former executive director of the Middle Country Coalition for Smart Growth, a nonprofit organization working to develop and revitalize the Middle Country community.

McCormack said the idea to create a dog park in Middle Country goes back to when the group was putting together the Middle Country Sustainable Community Plan. In the 2008 community plan, which listed the community’s assets and needs, a dog park was listed as an item the community expressed “significant interest” in.

For the last three months, McCormack said residents involved with the initiative have really tried to move forward with it. A car-wash fundraiser was held recently, and Rabinowitz said she wants to continue to raise funds and hold monthly car washes over the summer. Another fundraiser will be held at the Middle Country Beer Garden in July. Rabinowitz said Central Suffolk Paws is also looking for sponsors for the dog park, with the hope of purchasing things like benches for the park and developing it further.

McCormack said residents could also volunteer to help out, especially on Saturday, May 18, when the Town of Brookhaven will hold its sixth annual Great Brookhaven Clean Up at various locations throughout the town, including the soon-to-be dog park’s location. The property sometimes attracts unwanted visitors, who leave behind alcohol bottles and other trash.

“Volunteers are more than welcome,” McCormack said. “The more we can get [the property] clean, the less we have to rely on the town.”

For updates on the park’s progress or to find out more information, residents can visit the Central Suffolk Paws Facebook group or email cspaws@gmail.com.

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Comparing bacteria’s genes and computer code brought about some scientific surprises

A computational systems biologist, Sergei Maslov recently showed what makes some pieces of computer code critically important to computer systems, the same way certain genes are common and important among bacteria.

“I was working with Linux, which has real similarities with bacteria,” said Maslov, who is a computational biology group leader at the Department of Biosciences at Brookhaven National Laboratory and an external faculty member at Stony Brook. Engineers can “reuse packages created by other engineers, who could be on another continent. It’s a complex interdependency.”

The most frequently used parts are also among the most functionally important ones. Scientists can measure their importance by looking at how many other components depend on them for their operation.

“I was rather shocked by how much is similar” when comparing bacterial genes and computer codes, he said. His results were recently published in the Proceedings of the National Academy of Sciences.

As a systems biologist, Maslov typically works with large amounts of data to make sense of patterns.

“The models I create explain the real world around us. I am very interested in complex networks,” he said. “The first challenge is to get data describing those networks.”

Fortunately, he said, the amount of publicly available data has grown enormously over the last two decades. Indeed, in his study, Maslov looked at over 2 million Linux computers and 500 bacterial species.

Maslov is one of four principal investigators in a large Department of Energy-sponsored project called KBase.

The project, which started a year and a half ago, includes researchers from a wide range of institutions. Maslov leads the group of scientists based at BNL, Cold Spring Harbor Laboratory and Yale.

One of the goals of KBase is to provide a “solid platform that supports predictive biology in a framework that does not require users to learn separate systems to formulate and answer questions spanning a variety of topics in systems biology research,” according to the KBase website.

The application of that predictive research includes handling biological problems in energy and the environment.

In addition to his work with KBase, Maslov has looked at stock price fluctuations, Internet connectivity data, World Wide Web pages, hyperlinks and many others.

He is currently analyzing food webs by using data in KBase that describes microbial communities and uses network analysis tools to make sense of microbe-microbe and plant-microbe interactions.

“I view food webs as a network of interacting objects,” he said. “You can study all the individual microbes in a food web very well, but still not understand how they interact.”

He looks at the pattern of connections among species, to determine which species might be more important. Long-term, he said he wants to understand how certain perturbations — or changes — will cascade down food webs.

“We want to understand which perturbations lead to minor changes and which will lead to large-scale systemwide changes,” he said.

Maslov said the biggest lesson he’s learned from studying the patterns in evolution is that “if you want to design software or any other complex system, make it evolvable. Make sure it doesn’t become too rigid.”

Maslov has lived in many towns since he came to Long Island two decades ago, including in Stony Brook, Sound Beach, and Dix Hills. Indeed, when he resided in Dix Hills, he lived in saxophone great John Coltrane’s house, which is now being turned into a museum.

Maslov’s wife Olga Maslova, a costume designer, is working on sets and costumes for an opera in Boston. Maslova left for the first meeting with producers on the day of the marathon, but was on the Long Island ferry during the attack.

The couple lives in Shoreham with their 10-year-old son Leo and their 6-year-old Alexander.

Maslov grew up in Moscow and appreciates the proximity of Long Island to the City.

As for his research, “We allow the people who do experiments on organisms to recommend particular genes they should pay attention to, maybe provide some guidance on how best to optimize a plant to survive in drought or good soil conditions. We organize the data and allow researchers to work with it.

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Testing a bar-coding approach as a cost-effective way to study how neurons interact

Using the three pounds of matter between his ears, Tony Zador came up with an idea. Instead of looking closely at all the individual neurons to understand the connections in the brain, he would take advantage of a cost-effective way to monitor those links.

A professor of biology and program chair of neuroscience at Cold Spring Harbor, Zador has created a bar-coding system in which he hopes to label each neuron. He also plans to monitor the connections among those neurons.

Scientists “know a lot about individual neurons, but far less about how they’re wired up,” Zador said. “Much of the scientific community believes that disorders like autism and schizophrenia arise from problems with wiring. My core interest is in understanding how we go from a wired-up brain to behavior.”

The way our brains work has become a new frontier in science, as President Obama announced a new brain initiative. The effort is designed to enhance our understanding of the mind, help combat diseases and disorders, and lead to new companies and jobs.

Zador’s bar-coding approach differs from that of many other researchers.

“Very smart people at great places — MIT, Harvard, Stanford — are all trying to develop the technology to put together a wiring diagram using electron microscope images. The problem is, even if they succeed, it’s incredibly expensive,” Zador said.

The cost of sequencing genes has gone down precipitously over the last decade. About 10 years ago, the cost for determining the order of base pairs for a person was about $1 billion. Today, that is now about $1,000 to $3,000, Zador estimated.

“If we could somehow convert the problem of figuring out the connectivity of the brain to a problem of sequencing DNA, then this problem, in principal, would be quick and cheap,” he said.

The way this works is by studying mice in which each neuron has a unique DNA label (created by his lab). He believes those labels will not affect the circuitry of the brain, although he plans to test that hypothesis. By looking at these circuits, he will be able to get an idea of how they connect.

The science is a “work in progress,” he said. He’s about to submit a proof of principle that shows how the process works.

If and when this system works and the researchers can determine the typical connections in the brain, they might start looking at the brains in a mouse model of autism.

“It’s quite plausible to believe we’ll get a much better understanding of what’s going on in the brain of someone with autism or schizophrenia if we can understand what happens in a mouse that has those genes disrupted in the way they are in humans,” he said.

Knowing what the normal circuit looks like is a starting point that opens up a wide range of questions.

At this point, one of the theories about autism is that some of the longer-range neuronal connections are impaired, while the local connections are more active.

If that turns out to be the case, scientists might be able to use different drugs to enhance one type of connection while quieting the effect of another.

While Zador came up with an idea he believes will work, his background in physiology and computational and theoretical science didn’t prepare him to develop the molecular biology techniques he’d need for his research. An avid runner who covers five or six miles each day — either outside the lab or on a treadmill — Zador used to run alone.

For the last five or six years, he’s run a few times a week with Josh Dubnau. A colleague at CSHL, Dubnau provides a “one hour tutorial” on molecular biology with each run — while discussing other scientific challenges and, on occasion, politics.

A resident of Laurel Hollow, which is within walking distance of the lab, Zador and his wife Kathy Shamoun, who practices Chinese medicine at Cold Spring Harbor and is also a childbirth educator, have two sons, 7-year-old Ronin and 3-year-old Bowie.

Zador recognizes his research is going in a different direction from other scientists.

“What are the chances it’s going to work?” he wonders. “I’m betting my career on it. I’m enthusiastic and optimistic.”

 

Correction:

In the article “BNL’s James Dickerson: facilitating nanotechnology” that ran last week, we incorrectly reported how long the Center for Functional Nanomaterials has been open. The building has been open for 5 years. We regret the error.

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Significant improvements were seen in one month with lifestyle modifications

Chronic kidney disease is on the rise in this country. In a study that looked at data from the National Health and Nutrition Examination Survey, prevalence of chronic kidney disease (CKD) increased more than 30 percent from 1988 to 2004 (JAMA. 2007;298:2038-2047). Early-stage (mild) CKD is no exception and may not be getting enough attention. In this article, we will look beyond the more obvious causes of mild chronic kidney disease, such as diabetes, smoking, aging, obesity and high blood pressure (JAMA. 2004;291:844-850).

Why is early-stage CKD so important? It is associated with a 40 percent increased risk of developing cardiovascular events, such as heart attacks (N Engl J Med. 2004;351:1296-1305). It also significantly increases the risk of peripheral artery disease (PAD). Those with decreased kidney function have a 24 percent prevalence of PAD, compared to 3.7 percent in those with normal kidney function (Circulation. 2004;109:320–323). Of course, it can lead ultimately to end-stage renal (kidney) disease, requiring dialysis and potentially a kidney transplant.

One of the problems with early-stage CKD is that it tends to be asymptomatic. However, there are simple tests, such as a basic metabolic panel and a urinalysis, that will indicate whether a patient may have mild chronic kidney disease. These indices for kidney function include an estimated glomerular filtration rate (eGFR), creatinine level and protein in the urine. While the other two indices have varying ranges depending on the laboratory used, a patient with an eGFR of 30 to 59 mL/minute/1.73 m2 is considered to have mild disease. The eGFR and the kidney function are inversely related, meaning as eGFR declines, the more severe the chronic kidney disease.

What can be done to stem early-stage CKD, before complications occur? There are several studies that have looked at medications and lifestyle modifications and their impacts on its prevention, treatment and reversal.

Let’s look at the evidence.

 

Medications

Allopurinol is usually thought of as a medication for the prevention of gout. However, in a randomized controlled trial, the gold standard of studies, the results show that allopurinol may help to slow the progression of CKD, defined in this study as an eGFR less than 60 mL/min/1.73 m2 (Clin J Am Soc Nephrol. 2010 Aug;5:1388-1393). The group using 100 mg of allopurinol showed significant improvement in eGFR levels (a 1.3 mL/minute per 1.73 m2 increase) compared to the control group (a 3.3 mL/minute per 1.73 m2 decrease) over a two-year period. There were 113 patients involved in this study. The researchers concluded that there was a slow progression of CKD with allopurinol. Allopurinol also decreased cardiovascular risk by 71 percent.

Fibrates are a class of drug usually used to boost HDL (“good”) cholesterol levels and reduce triglyceride levels, another cholesterol marker. Fibrates have gotten negative press recently for not showing improvement in cardiovascular outcomes. However, in patients with mild to moderate CKD, a meta-analysis (a group of 10 studies) recently showed a 30 percent reduction in major cardiovascular events and a 40 percent reduction in the risk of cardiovascular mortality with the use of fibrates (J Am Coll Cardiol. 2012 Nov. 13;60:2061-2071). This is important, since patients with CKD are mostly likely to die of cardiovascular disease.

The authors concluded that fibrates seem to have a much more powerful beneficial effect in CKD patients, as opposed to the general population. So, there may be a role for fibrates after all.

 

Lifestyle modifications

Fruits and vegetables may play a role in helping patients with CKD. In a recent study, the results showed that fruits and vegetables work as well as sodium bicarbonate in improving kidney function by reducing metabolic acidosis levels (Clin J Am Soc Nephrol. 2013;8:371-381).

What is the significance of metabolic acidosis? It means that body fluids become acidic and it is associated with chronic kidney disease. The authors concluded that both sodium bicarbonate and a diet including fruits and vegetables were renoprotective, helping to protect the kidneys from further damage in patients with CKD. Alkali diets are primarily plant-based, although not necessarily vegetarian or vegan-based diets. Animal products tend to cause an acidic environment. The study was one year in duration, however, though the results were impressive, the study was small, with 77 patients.

Sodium rears its ugly head yet again. Red meat is not thought of positively, and animal fat is not far behind. In the Nurses’ Health Study, the results show that animal fat, red meat and salt all negatively impact kidney function (Clin J Am Soc Nephrol. 2010; 5:836-843). The risk of protein in the urine, a potential indicator of CKD, increased by 72 percent in those participants who consumed the highest amounts of animal fat compared to the lowest, and by 51 percent in those who ate red meat at least twice a week. With higher amounts of sodium, there was a 52 percent increased risk of having lower levels of eGFR.

The most interesting part with sodium was that the difference between higher mean consumption and the lower mean consumption was not that large, 2.4 grams compared to 1.7 grams. In other words, the difference between approximately a teaspoon of sodium and three quarters of a teaspoon was responsible for the decrease in kidney function.

In my practice, when CKD patients follow a vegetable-rich, nutrient-dense diet, there are substantial improvements in kidney functioning. For instance, for a recent patient, his baseline eGFR was 54 mL/min/1.73 m2. After one month of lifestyle modifications, his eGFR improved by 9 points to 63 mL/min/1.73 m2, which is a return to “normal” functioning of the kidney. However, this is an anecdotal story and not a study.

Therefore, it is important to have your kidney function checked with mainstream tests. If the levels are low, we should address the issue through medications and/or lifestyle modifications to manage and reverse early-stage CKD. However, lifestyle modifications don’t have the negative side effects of medications. Don’t wait until symptoms and complications occur. In my experience, it is much easier to treat and reverse a disease in its earlier stages, and CKD is no exception.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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