Methods to repair kidney cells, assess kidney function on the horizon

April 16, 2013, Medical College of Georgia
Methods to repair kidney cells, assess kidney function on the horizon
Drs. Michael P. Madaio (from left), Nino Kvirkvelia and Tracy L. McGaha may have found a way to block kidney-destroying inflammation and help damaged kidney cells recover. Credit: Phil Jones, Georgia Regents University

Researchers may have found a way to block kidney-destroying inflammation and help damaged kidney cells recover.

In a related study, they report progress on a non- to assess how much function has survived a serious bout of inflammation or a chronic problem like .

The could help physicians make hard choices about whether a patient has enough kidney function left to benefit from treatment or whether dialysis or a transplant is in their future, said Dr. Michael P. Madaio, and Chairman of the Department of Medicine at the Medical College of Georgia at Georgia Regents University.

If the kidneys can be saved, this approach could also aid optimal delivery of drugs directly to ailing kidney filters.

Significant infections, an oxygen-depriving or injury, diabetes and uncontrolled hypertension all can take a serious or deadly toll on the kidneys.

In an effort to better protect them, researchers induced acute kidney inflammation, or nephritis, in mice then gave them prostaglandin E2 . The kidneys' filtering units promptly recovered. "The cells got better, the kidneys got better," said Madaio, corresponding author of the study in the American Journal of Physiology-Renal Physiology.

While prostaglandins are better known as natural pro-inflammatory lipid compounds, prostaglandin E2 has an anti-inflammatory effect. The researchers suspected – and found – it also had the bonus regenerative properties.

"We've already got numerous ways to block inflammation, but what we hope is the magic here is the ability to also help injured recover," Madaio said.

In the related study, they found what appears to be a good indicator of kidney function that could help physicians and patients optimize treatment. "It's hard to determine the extent of disease from the current ways we measure ," Madaio said. If it seems like treatment should be tried regardless, current regimes such as immunosuppressive drugs that block inflammation, for example, have serious side effects, including leaving patients vulnerable for additional infections.

In the search for a better way, researchers put a fluorescent tag on a human monoclonal antibody for a collagen found only in the kidney, lungs, and ears; injected it in mice with active kidney disease; then looked for antibody-binding in the kidney, said Dr. Tracy L. McGaha, MCG immunologist and co-corresponding author of the study in Kidney International.

This collagen is part of the base structure of kidney filters and its triple-helix configuration means the collagen molecules must hook together to work. The antibody the researchers used recognizes the stalks where collagen molecules connect, so it only binds when that bond is broken, an early indicator of kidney damage and lost function.

"When you have inflammation in the kidneys, the ends break apart, expose that little domain and the antibody can recognize it," McGaha said. The tagging system worked in the mice as well as tissue taken from patients with various kidney diseases.

This affinity for kidney filters means the antibody also could be used to directly deliver therapy to the filters, enhancing efficacy while reducing side effects. Similar approaches already are being used in cancer, McGaha said. may one day be one of those targeted therapies, he and Madaio noted.

Unfortunately, there are typically no early signs of kidney injury. When physicians suspect it, they look in the blood for levels of substances such as creatinine, a byproduct of metabolism which kidneys normally eliminate, and/or look to see if the normally fist-sized organs have shrunk, a sign of scarring. By the time either occurs, serious kidney damage has been done, Madaio said. Kidney biopsies, which provide a limited sample size and have their own set of complications, provide limited information as well.

At least in this early stage, the tagged antibody seems to have the current methods beat. "Before you see increases in protein excretion in the urine, before you see changes in the blood chemistry, you see this exposure," McGaha said.

To translate to humans, the labeled antibodies likely would need to be paired with powerful imaging technology such as the PET scanner to enable a full assessment of both kidneys, McGaha said. Antibodies, which are part of the normal immune response, also will have to be engineered so they only bind to their target, and don't also drive more inflammation, which is their usual role.

Every day, the kidneys filter about a quarter of the blood in the body, deciding what to keep, such as nutrients, and what to flush, such as excess sodium or a toxin. This aggressive job makes the kidneys particularly vulnerable to changes in blood pressure, increased inflammation and or toxins circulating in the body.

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not rated yet Apr 16, 2013
In 2003 I was hospitalized with complete kidney failure. Zero! Three weeks later I was discharged and put on dialysis 3Xw and put on the transplant list.

I did not want a transplant and live the rest of my life on immune suppressants. I spent all my waking hours online looking for solutions to my problem. I had no results until I redefined my problem as an overall inflammatory problem. Then I discovered many natural anti-inflammatory nutrients.

I began taking them with the advice of a nutritionist and within two months I was told that my kidney function had returned to the point where I would no longer need dialysis. One of the nurses who worked there (large dialysis center) said she had worked there 7 1/2 years and I was only the third person she had seen walk out of there without a transplant or died.

To this day I watch my diet very carefully and know that the medical profession is still mired in the dark ages. My doctor was amazed when I told him I was off dialysis. I never...
not rated yet Apr 16, 2013
...went back to him again. He taught at a university hospital and always came around in the morning with a gaggle of little ducks wagging their tails behind them, hanging on every word he said.

I never began to get better till I decided to take control of my own health. It was the doctor's medications that were killing me slowly.

In a book about the cancer industry, the author pointed out that a researcher had the best chance of getting funded if they made sure the only thing their research would show was the need for more research. If you find a cure, it's game over and hundreds of thousands of people will have to find new jobs.

In my meanderings through the net I found something interesting. Smallpox is not contagious. It was spread by the bite of an infected bedbug. This finding was duly reported to the appropriate health officials where it was quietly allowed to die. It seems there's too much money in vaccinations to let a little thing like facts get in the way of profits.
not rated yet Apr 20, 2013
This sounds a little self important. There are many reasons that kidneys go bad. We're all very glad that you stumbled upon a way to improve, but to cast such a wide net over a caring profession trying to help you is dangerous. And I'm sure all patients would respond exactly as you have, notwithstanding their own complex health issues. I'm sure all teachers, firefighters, and police (not to mention those involved in other public services) are all out to scam you, too.

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