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Bioartificial kidney under study at MCG

Whether a bioartificial kidney containing billions of donor kidney cells will help intensive care patients with kidney failure survive is under study at the Medical College of Georgia.

MCG Medical Center has joined a study taking place in intensive care units across the country to evaluate the efficacy of the renal assist device, says Dr. Harold M. Szerlip, MCG nephrologist specializing in acute renal failure and a principal investigator on the study.

"If you have renal failure in the ICU, your mortality is extremely high," Dr. Szerlip says. "Anywhere from 50 to 70 percent of those patients die and over the past 20 years, despite dialysis, that has not changed much."

He hopes the new device, developed by Dr. H. David Humes at the University of Michigan, can help turn the tide for some patients by more closely mimicking the many important functions of the kidney.

In ICUs today, doctors may opt for newer continuous dialysis therapies in which patients with renal failure receive dialysis around the clock. With more standard intermittent therapy, patients get several hours of dialysis three to four times a week.

Since kidneys are constantly working, it may seem logical that longer dialysis is a better option, but, in fact, the issue has not been scientifically analyzed. This month, Dr. Szerlip and MCG Medical Center will join a Department of Veterans Affairs and National Institutes of Health study to do just that.

But no matter how long dialysis is given, it only replicates a fraction of the work of the kidneys, which are involved in diverse functions ranging from regulating vitamin D to modulating the immune response. "Existing forms of dialysis have only replaced the ability of the kidneys to rid the body of waste products and correct abnormalities in blood chemistry; they don't replace kidney function, " says Dr. Szerlip.

The kidneys also secrete hormones, help determine how the body metabolizes calcium and phosp horus, stimulate red blood cell production, play a role in blood pressure regulation and clear and metabolize cytokines that help direct the immune system.

The new device for kidney failure adds billions of kidney cells that can perform many of these important kidney functions. Human proximal tubule cells are collected from kidneys obtained by the National Disease Research Interchange, a nonprofit organization that provides researchers with tissues and organs anatomically unsuitable for transplant.

The cells are grown into the walls of thousands of hollow fibers contained in a cartridge similar to those used for traditional dialysis.

With dialysis, a patient's blood runs through the fibers and a solution with the normal composition of electrolytes runs on the outside. Through osmosis, waste products in the blood migrate across the fibers into the solution. The now-dirty solution is discarded and the cleaner blood is given back to the patient. In the study, all patients receive this standard approach to cleaning the blood.

But two-thirds of the study participants take the additional step of having the liquid portion of their filtered blood, called an ultrafiltrate ?which would contain remaining toxins, electrolytes, mediators of inflammation and such ?removed. The liquid is run through the cell-lined fibers of a second cartridge, while the blood is run on the outside of the fibers.

"(These cells) reabsorb substances from the ultrafiltrate ?and put them back into the blood on the outside of the fiber, which is pumped back into the body. The stuff that isn't pumped out is just like urine: it goes in the toilet," Dr. Szerlip says.

Preliminary findings on 10 patients at the University of Michigan Medical Center and Cleveland Clinic Foundation showed the device was safe and produced desired results such as reducing circulating inflammatory mediators. Study results were published in the October 2004 issue of Kidney Internatio nal.

The trial now underway is looking at the efficacy of the device over 72 hours, although researchers say that if the device is eventually approved by the Food and Drug Administration, it likely would be used as long as the patient is in failure.

Kidneys require a lot of oxygen and energy to perform their endless task, which makes them easy targets in the ICU, Dr. Szerlip explains. As examples, kidneys can become ischemic and begin to fail if blood pressure drops because of a long surgery with significant blood loss. Infection can further reduce blood flow to the kidneys. Ironically, some antibiotics patients need for these infections also can harm the kidneys. Even the contrast medium needed to study kidney function can be toxic. "I have seen healthy people on antibiotics for urinary tract infections develop renal failure; that's not uncommon, but it's most dreaded in the critically ill patient," Dr. Szerlip says.


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Source:Medical College of Georgia


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