Methods To Repair Kidney Cells, Assess Kidney Function On The Horizon

[Pendragon]

Methods To Repair Kidney Cells, Assess Kidney Function On The Horizon
18 Apr 2013

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-invasive method to
assess how much kidney function has survived a serious bout of
inflammation or a chronic problem like high blood pressure.

The diagnostic tool 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, nephrologist 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 critical illness 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 kidney
cells 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 kidney function," 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. Prostaglandin E2 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.

The research was funded by the National Institutes of Health. Madaio
also is co-corresponding author on the antibody study in Kidney
International and Dr. Kapil Chaudhary, a GRU graduate student, is
first author. Dr. Nino Kvirkvelia, research scientist in the MCG
Department of Medicine, is first author on the prostaglandin study.
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References:
Source: Georgia Regents University


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MLA
Georgia Regents University. "Methods To Repair Kidney Cells, Assess
Kidney Function On The Horizon." Medical News Today. MediLexicon,
Intl., 18 Apr. 2013. Web.
24 Apr. 2013. <http://www.medicalnewstoday.com/releases/259251.php>
APA
Georgia Regents University. (2013, April 18). "Methods To Repair
Kidney Cells, Assess Kidney Function On The Horizon." Medical News
Today. Retrieved from
http://www.medicalnewstoday.com/releases/259251.php.
Please note: If no author information is provided, the source is cited
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