Tag: kidney

Novel drug therapy from University Hospitals of Cleveland shows promise for improving kidney transplants

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Researchers from Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center (UH), Cleveland Clinic and Lifebanc (a Northeast Ohio organ-procurement organization) have developed a new way to preserve donated kidneys–a method that could extend the number and quality of kidneys available for transplant, saving more people with end-stage renal disease, more commonly known as “kidney failure.”

The team identified a drug–ethyl nitrite–that could be added to the preservation fluid to generate tiny molecules called S-nitrosothiols (SNOs), which regulate tissue-oxygen delivery. This, in turn, restored flow-through and reduced resistance within the kidney. Higher flow-rates and lower resistance are associated with better kidney function after transplantation.

Their research was funded by a grant from the Roche Organ Transplant Research Foundation and recently published in Annals of Surgery.

The United States has one of the world’s highest incidences of end-stage renal disease, and the number of afflicted individuals continues to increase. The prevalence of end-stage renal disease has more than doubled between 1990 and 2016, according to the Centers for Disease Control.

The optimal treatment is a kidney transplant, but demand far exceeds supply. Additionally, donation rates for deceased donors have been static for several years, despite various public-education campaigns, resulting in fewer kidneys available for transplant. And while the proportion and number of living donors has increased, this latter group still only makes up a small percentage of recovered kidneys for transplant.

Increasing the number of kidneys available for transplant benefits patients by extending lifespans and/or enhancing quality of life as well as the potential for reducing medical costs (a transplant is cheaper than ongoing dialysis). To help improve outcomes for kidney transplant patients, the team explored ways to extend the viability of donated kidneys.

Improvements in surgical techniques and immunosuppression therapies have made kidney transplants a relatively common procedure. However, less attention has been paid to maintaining/improving kidney function during the kidney-transport phase.

“We addressed this latter point through developing enhanced preservation methods,” said senior author James Reynolds, professor of Anesthesiology and Perioperative Medicine at Case Western Reserve School of Medicine and a member of the Harrington Discovery Institute at UH.

For decades, procured kidneys were simply flushed with preservation solution and then transported in ice-filled coolers to the recipient’s hospital. But advances in pumping technology slowly changed the field toward active storage, the preferred method for conveying the organ from donor to recipient.

“However, while 85% of kidneys are now pumped, up to 20% of kidneys are determined to be unsuitable for transplant during the storage phase,” said Kenneth Chavin, professor of surgery at the School of Medicine, chief of hepatobiliary and transplant surgery and director of the UH Transplant Institute.

“For several years, our team has directed research efforts toward understanding and improving the body’s response to medical manipulation,” Reynolds said. “Organ-donor physiology and ‘transport status’ fit well within this metric. We identified a therapy that might improve kidney perfusion, a significant factor in predicting how the organ will perform post-transplant.”

Previous work by Reynolds and long-time collaborator Jonathan Stamler, the Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation and president of the Harrington Discovery Institute, determined that brain death significantly reduces SNOs, which impairs blood-flow and tissue-oxygenation to the kidneys and other commonly transplanted organs. The loss of SNOs is not corrected by current preservation fluids, so impaired flow through the kidneys continues during storage and transport.

http://7thspace.com/headlines/1099047/novel_drug_therapy_shows_promise_for_quality__quantity_of_kidneys_available_for_transplant.html

They matched on a dating site and got married. He needed a kidney, and they matched again.

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By Lauren M. Johnson

It was a match made in heaven, or at least eharmony told them so. But Lisa and Dan Summers didn’t know how compatible they really were.

Before the Summers met and fell in love after meeting online, Dan, who is in his 30’s, had a kidney condition that was discovered in his 20s.

“I knew about 10 years ago that there was going to be some trouble sometime in the future,” Dan told CNN affiliate KTXL. “And they thought it was going to be when I was in my 50s or 60s, and it ended up hitting last year.”

He needed a transplant, and come to find out Lisa was a match. The odds? One in 100,000, doctors said.

“It’s like being next to a stranger on a train, matching them and then also falling in love on top of it, you know,” Lisa said. “There was like this sense that it was going to work.”

On August 22 at UCSF Medical Center near their home in Auburn, California, the transplant was successfully performed, and Lisa’s kidney was accepted by Dan’s body.

A new outlook

Though the Summers are back to normal with their son Jasper, they have a new appreciation for life.

“Being able to see him in front of me just holding my son’s hand or when he lifts him or those fun moments,” Lisa said. “It’s like there’s an extra appreciation to it, that my son gets to have his father growing up, you know.”

The Summers are now also advocating for kidney donation and are firm believers that the sacrifice can go a long way.

“There’s a shortage of donors that are out there right now and there’s a number of people that are in kidney failure. And dialysis is not a fun thing,” Dan said. “On a live donor they can get 10 to 20, sometimes 30 years if the match is really good.”

https://www.cnn.com/2019/12/05/us/wife-is-husbands-kidney-donor-trnd/index.html

Re-programming the body’s energy pathway boosts kidney self-repair

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A team of researchers led by Jonathan Stamler, MD, of Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, has discovered a pathway for enhancing the self-repair efforts of injured kidneys. The finding may pave the way for new drugs to stop or even reverse the progression of serious kidney disease in humans — and other potentially lethal conditions of the heart, liver, and brain as well.

Kidneys filter waste and excess fluid from the blood, excreting the unsafe molecules in urine. As kidneys are injured or fail, waste builds up, potentially resulting in death.

The newly-discovered pathway involves reprogramming the body’s own metabolism in order to save damaged kidneys. Normally, a process called glycolysis converts glucose from food into energy, which is necessary for life to continue. But the new discovery shows that when tissue is injured, the body can switch the process in to one of repair to damaged cells.

Until now, the mechanisms by which the body switches between energy generation (for maximal performance) and repair (in injury) were poorly understood. Moreover, the body rarely maximizes the potential for repair, usually favoring energy production.

In the new findings, published online today and in the November 29th issue of Nature, the science team discovered how to intensify the switching process, resulting in a cascade of tissue-repair molecules that successfully stopped progression of kidney disease in mice.

“When injured, the body slows down use of sugar for energy, using it for repair instead,” said Stamler. “We show that we can control and amplify this process by shunting glucose away from energy generation into pathways that protect and repair cells. By giving a ‘lift and push’ to the body’s own self-healing we improve lifespan of injured animals. We can think of it as a blueprint for new lines of future therapy against injured and damaged tissue.”

Normally, when cells break down fat, sugars, and proteins into glucose, the three substances are converted into intermediate products that move into the mitochondria, the powerhouse of cells, providing fuel for life. Stamler’s team reports that things work very differently in injured tissues: in the kidneys for example, the body triggers a “Plan B,” converting the glucose into new molecules that carry out cell repair instead.

Stamler and colleagues found that a protein called PKM2 controls whether fuel (glucose) is used to power the cell or shift into repair mode. Disabling PKM2 resulted in a significant increase in cell-repair and a concomitant decrease in energy-generation. “After injury or disease, the body tries to disable the PKM2 protein in order to divert glucose into recovery mode. In our research, we amplified its inhibition. This resulted in significant protection against kidney injury in mice.”

A key molecule in the process is nitric oxide (NO). It was already known that NO protects kidneys and other tissue. NO is the active ingredient in nitroglycerine used for addressing heart disease so it was assumed that NO worked by dilating blood vessels. But the research team found that NO attached to a critical molecule called Co-enzyme A — known as a metabolite — linked to the glycolysis and energy production. Co-enzyme A binds to and transports NO into many different proteins, including PKM2, “turning them off.” This determines whether the kidney cells are using their pathways for energy or repair.

In addition to finding that adding NO to PKM2 activates repair, Stamler’s team found that a protein called AKR1A1 subsequently removes the NO from PKM2, re-activating a robust energy-generating process. This reversal, after healing is complete, allows glucose to be converted efficiently into fuel. “This helps explain why people regain the capacity to do strenuous activity after they recover from an injury or illness,” said Stamler. When the research team disabled AKR1A1, the kidneys remained in repair mode and were highly protected from disease.

Thirty million people — 15 percent of the adult population — are estimated to have kidney disease in the United States. Causes include medical conditions such as high blood pressure and diabetes, as well as chemotherapy and dyes used in cardiac catherization.

Therefore, the goal is to develop drugs to inhibit PKM2 or AKR1A1. This could open up new healing possibilities for millions of people worldwide suffering from numerous conditions, injuries, and diseases, including heart disease, stroke, brain trauma and kidney disease.

https://www.sciencedaily.com/releases/2018/11/181128141657.htm

An explanation of blood sugar

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By Alina Bradford

Blood sugar, or glucose, is the main sugar found in blood. The body gets glucose from the food we eat. This sugar is an important source of energy and provides nutrients to the body’s organs, muscles and nervous system. The absorption, storage and production of glucose is regulated constantly by complex processes involving the small intestine, liver and pancreas.

Glucose enters the bloodstream after a person has eaten carbohydrates. The endocrine system helps keep the bloodstream’s glucose levels in check using the pancreas. This organ produces the hormone insulin, releasing it after a person consumes protein or carbohydrates. The insulin sends excess glucose in the liver as glycogen.

The pancreas also produces a hormone called glucagon, which does the opposite of insulin, raising blood sugar levels when needed. The two hormones work together to keep glucose balanced.

When the body needs more sugar in the blood, the glucagon signals the liver to turn the glycogen back into glucose and release it into the bloodstream. This process is called glycogenolysis.

When there isn’t enough sugar to go around, the liver hoards the resource for the parts of the body that need it, including the brain, red blood cells and parts of the kidney. For the rest of the body, the liver makes ketones , which breaks down fat to use as fuel. The process of turning fat into ketones is called ketogenesis. The liver can also make sugar out of other things in the body, like amino acids, waste products and fat byproducts.

Glucose vs. dextrose
Dextrose is also a sugar. It’s chemically identical to glucose but is made from corn and rice, according to Healthline. It is often used as a sweetener in baking products and in processed foods. Dextrose also has medicinal purposes. It is dissolved in solutions that are given intravenously to increase a person’s blood sugar levels.

Normal blood sugar
For most people, 80 to 99 milligrams of sugar per deciliter before a meal and 80 to 140 mg/dl after a meal is normal. The American Diabetes Association says that most nonpregnant adults with diabetes should have 80 to 130 mg/dl before a meal and less than 180 mg/dl at 1 to 2 hours after beginning the meal.

These variations in blood-sugar levels, both before and after meals, reflect the way that the body absorbs and stores glucose. After you eat, your body breaks down the carbohydrates in food into smaller parts, including glucose, which the small intestine can absorb.

Problems
Diabetes happens when the body lacks insulin or because the body is not working effectively, according to Dr. Jennifer Loh, chief of the department of endocrinology for Kaiser Permanente in Hawaii. The disorder can be linked to many causes, including obesity, diet and family history, said Dr. Alyson Myers of Northwell Health in New York.

“To diagnose diabetes, we do an oral glucose-tolerance test with fasting,” Myers said.

Cells may develop a tolerance to insulin, making it necessary for the pancreas to produce and release more insulin to lower your blood sugar levels by the required amount. Eventually, the body can fail to produce enough insulin to keep up with the sugar coming into the body.

It can take decades to diagnose high blood-sugar levels, though. This may happen because the pancreas is so good at its job that a doctor can continue to get normal blood-glucose readings while insulin tolerance continues to increase, said Joy Stephenson-Laws, founder of Proactive Health Labs (pH Labs), a nonprofit that provides health care education and tools. She also wrote “Minerals – The Forgotten Nutrient: Your Secret Weapon for Getting and Staying Healthy” (Proactive Health Labs, 2016).

Health professionals can check blood sugar levels with an A1C test, which is a blood test for type 2 diabetes and prediabetes, according to the U.S. National Library of Medicine. This test measures your average blood glucose, or blood sugar, level over the previous three months.

Doctors may use the A1C alone or in combination with other diabetes tests to make a diagnosis. They also use the A1C to see how well you are managing your diabetes. This test is different from the blood sugar checks that people with diabetes do for themselves every day.

In the condition called hypoglycemia, the body fails to produce enough sugar. People with this disorder need treatment when blood sugar drops to 70 mg/dL or below. According to the Mayo Clinic, symptoms of hypoglycemia can be:

Tingling sensation around the mouth
Shakiness
Sweating
An irregular heart rhythm
Fatigue
Pale skin
Crying out during sleep
Anxiety
Hunger
Irritability


Keeping blood sugar in control

Stephenson-Laws said healthy individuals can keep their blood sugar at the appropriate levels using the following methods:

Maintaining a healthy weight

Talk with a competent health care professional about what an ideal weight for you should be before starting any kind of weight loss program.

Improving diet

Look for and select whole, unprocessed foods, like fruits and vegetables, instead of highly processed or prepared foods. Foods that have a lot of simple carbohydrates, like cookies and crackers, that your body can digest quickly tend to spike insulin levels and put additional stress on the pancreas. Also, avoid saturated fats and instead opt for unsaturated fats and high-fiber foods. Consider adding nuts, vegetables, herbs and spices to your diet.

Getting physical

A brisk walk for 30 minutes a day can greatly reduce blood sugar levels and increase insulin sensitivity.

Getting mineral levels checked

Research also shows that magnesium plays a vital role in helping insulin do its job. So, in addition to the other health benefits it provides, an adequate magnesium level can also reduce the chances of becoming insulin-tolerant.

Get insulin levels checked

Many doctors simply test for blood sugar and perform an A1C test, which primarily detects prediabetes or type 2 diabetes. Make sure you also get insulin checks.

https://www.livescience.com/62673-what-is-blood-sugar.html#?utm_source=ls-newsletter&utm_medium=email&utm_campaign=05272018-ls

New research shows that high salt diet suppresses weight gain in mice on a high fat diet

On By A.P.In cardiovascular disease, diet, Iowa, Iowa City, MedicineLeave a comment


Dr. Justin Grobe, PhD


Dr. Michael Lutter, MD PhD

In a study that seems to defy conventional dietary wisdom, University of Iowa scientists have found that adding high salt to a high-fat diet actually prevents weight gain in mice.

As exciting as this may sound to fast food lovers, the researchers caution that very high levels of dietary salt are associated with increased risk for cardiovascular disease in humans. Rather than suggest that a high salt diet is suddenly a good thing, the researchers say these findings really point to the profound effect non-caloric dietary nutrients can have on energy balance and weight gain.

“People focus on how much fat or sugar is in the food they eat, but [in our experiments] something that has nothing to do with caloric content – sodium – has an even bigger effect on weight gain,” say Justin Grobe, PhD, assistant professor of pharmacology at the UI Carver College of Medicine and co-senior author of the study, which was published in the journal Scientific Reports on June 11.

The UI team started the study with the hypothesis that fat and salt, both being tasty to humans, would act together to increase food consumption and promote weight gain. They tested the idea by feeding groups of mice different diets: normal chow or high-fat chow with varying levels of salt (0.25 to 4 percent). To their surprise, the mice on the high-fat diet with the lowest salt gained the most weight, about 15 grams over 16 weeks, while animals on the high-fat, highest salt diet had low weight gain that was similar to the chow-fed mice, about 5 grams.

“We found out that our ‘french fry’ hypothesis was perfectly wrong,” says Grobe, who also is a member of the Fraternal Order of Eagles Diabetes Research Center at the UI and a Fellow of the American Heart Association. “The findings also suggest that public health efforts to continue lowering sodium intake may have unexpected and unintended consequences.”

To investigate why the high salt prevented weight gain, the researchers examined four key factors that influence energy balance in animals. On the energy input side, they ruled out changes in feeding behavior – all the mice ate the same amount of calories regardless of the salt content in their diet. On the energy output side, there was no difference in resting metabolism or physical activity between the mice on different diets. In contrast, varying levels of salt had a significant effect on digestive efficiency – the amount of fat from the diet that is absorbed by the body.

“Our study shows that not all calories are created equal,” says Michael Lutter, MD, PhD, co-senior study author and UI assistant professor of psychiatry. “Our findings, in conjunction with other studies, are showing that there is a wide range of dietary efficiency, or absorption of calories, in the populations, and that may contribute to resistance or sensitivity to weight gain.”

“This suppression of weight gain with increased sodium was due entirely to a reduced efficiency of the digestive tract to extract calories from the food that was consumed,” explains Grobe.

It’s possible that this finding explains the well-known digestive ill effects of certain fast foods that are high in both fat and salt, he adds.

Through his research on hypertension, Grobe knew that salt levels affect the activity of an enzyme called renin, which is a component in the renin- angiotensin system, a hormone system commonly targeted clinically to treat various cardiovascular diseases. The new study shows that angiotensin mediates the control of digestive efficiency by dietary sodium.

The clinical usefulness of reducing digestive efficiency for treating obesity has been proven by the drug orlistat, which is sold over-the-counter as Alli. The discovery that modulating the renin-angiotensin system also reduces digestive efficiency may lead to the developments of new anti-obesity treatments.

Lutter, who also is an eating disorders specialist with UI Health Care, notes that another big implication of the findings is that we are just starting to understand complex interactions between nutrients and how they affect calorie absorption, and it is important for scientists investigating the health effects of diet to analyze diets that are more complex than those currently used in animal experiments and more accurately reflect normal eating behavior.

“Most importantly, these findings support continued and nuanced discussions of public policies regarding dietary nutrient recommendations,” Grobe adds.

http://www.eurekalert.org/pub_releases/2015-06/uoih-hsp061115.php