2 replies to this topic

[kevin]

Link: http://www.medscape....icle/493081?rss

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First Human Trial of Bioartificial Kidney: A Newsmaker Interview With H. David Humes, MD
Laurie Barclay, MD

Nov. 4, 2004 — Editor's Note: The first human trial of a bioartificial kidney, reported in the October issue of Kidney International, suggests that this device may be life-saving for patients with acute renal failure. As in traditional dialysis, the bioartificial kidney includes a cartridge that filters the blood. This cartridge is connected to a renal tubule assist device (RAD) made of hollow fibers lined with renal proximal tubule cells, which reclaim electrolytes, salt, glucose, and water lost in traditional dialysis. Equally important, these human adult progenitor/stem cells control production of immune modulators known as cytokines.

In a phase 1/2 study at the University of Michigan Health System (UMHS) in Ann Arbor and the Cleveland Clinic Foundation in Ohio, the 10 patients enrolled had a mean risk of death during hospitalization of 86%, but six of them survived more than 30 days after treatment with the bioartificial kidney. In addition to acute renal failure, these patients had other life-threatening conditions, such as sepsis, multiple organ failure, acute respiratory distress syndrome, and postoperative complications. Treatment lasted up to 24 hours, with some patients stopping treatment earlier because of hypoglycemia, low platelet counts, or other medical complications.

To learn more about potential clinical applications of the bioartificial kidney, Medscape's Laurie Barclay interviewed lead study author H. David Humes, MD, a professor of internal medicine at the University of Michigan Medical School. Dr. Humes developed the RAD that is central to the bioartificial kidney, and development for future commercial applications is under license to Nephros Therapeutics Inc. This company is sponsoring an ongoing randomized, controlled, phase 2 trial of the RAD in acute renal failure, and the UMHS is planning a phase 1/2 trial for late 2005 to investigate the safety of the RAD in patients with end-stage chronic renal failure.

Medscape: What is the rationale behind the design of the bioartificial kidney?

Dr. Humes: First of all, we were thinking about what accounts for the poor survivability of patients in acute renal failure. In our lab's early work, we had isolated cells in the adult renal tubule that can repopulate a tubule which has become damaged. We were working with tissue-engineered constructs using those cells in our preclinical studies. Those experiments surprisingly pointed at something in the tubule cells as being responsible for modulating the hyperinflamed state that acute renal failure patients experience. We then recognized that by using these renal proximal tubule cells in treating acute renal failure, we could forestall the bad consequences of acute renal failure that are due to excessive inflammation. We could buy time for the patient's own kidney to recover.

Medscape: What are the advantages and disadvantages of using human adult stem cells in the bioartificial kidney?

Dr. Humes: We don't have any of the ethical or political dilemmas faced by researchers who work with fetal stem cells. And we have a pretty secure supply.

Medscape: How large is this device, and how easy or difficult is it to maintain?

Dr. Humes: This device is extracorporeal. It is designed for use as an adjunct to current hemofiltration technology in an intensive care unit. So it's basically the size of two continuous venovenous hemofiltration set-ups.

Medscape: Please describe the main findings of the phase 1/2 study using the bioartificial kidney.

Dr. Humes: [The] phase 1 [study] showed that the device promotes no adverse effects and is safe for further study. But, unlike a drug study, there were no "normal" control subjects — you wouldn't put a healthy person on continuous venovenous hemofiltration — so we also garnered early efficacy data. The cells remained viable and functioning. We observed in these patients the same cytokine modulation that we observed in animal studies five years ago, as well as other metabolic activity. We saw beneficial hemodynamic changes in these patients and indications that the treatment influenced increased native renal function. Six patients out of ten, who were expected to die, recovered.

Medscape: How do you anticipate the bioartificial kidney will compare with traditional dialysis or with kidney transplantation in terms of safety, efficacy, cost, and convenience?

Dr. Humes: You're thinking of our ultimate vision for an implantable bioartificial organ. The impact of that could, of course, be enormous, but it's premature to dwell on it. In the near future, however, we hope to see this adjunct treatment for acute renal failure save lives. At the same time, we expect it to hasten recovery and move patients out of the intensive care unit faster, thereby reducing treatment costs.

Medscape: What additional studies are planned?

Dr. Humes: We are finalizing a study to look at the use of the current device as an adjunct to dialysis to see whether the cells can control hyperinflammation in patients on chronic dialysis.

Medscape: How widespread do you believe use of the bioartificial kidney will become?

Dr. Humes: Acute renal failure develops in as many as 5% of hospitalized patients, and the mortality rate is now above 50%, so that's a large population of patients that could benefit. And if it proves as effective as it appears at controlling inflammatory states, it could further be applied toward other disorders in which hyperinflammation is a factor — burns, for instance.

Looking to the future, with this device we are gaining valuable experience [in] creating and delivering tissue-engineered treatments, applying the evolved capabilities of differentiated cells to treat complex, dynamic medical problems. So we're making strides toward the vision of an implantable device. There are over 350,000 cases of end-stage renal disease in the U.S., rising at a rate of 5% to 7% yearly. With obesity, diabetes, and hypertension now epidemic, we will be seeing a rise in the need for solutions.

Disclosures: The National Institutes of Health, the Michigan Life Sciences Corridor Fund, and Nephros Therapeutics Inc. funded this study. The RAD technology is owned by the University of Michigan and is licensed to Nephros Therapeutics Inc., a biotechnology spin-off company of the University of Michigan. Dr. Humes and two other authors are shareholders in Nephros.

Kidney Int. 2004;66(4):1578-1588

Reviewed by Gary D. Vogin, MD

[kevin]

Link: http://www.mcg.edu/n...Rel/Kidney.html

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Bioartificial Kidney Under Study at MCG
Story by Toni Baker
Photo by Phil Jones
Jan. 31, 2005

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 phosphorus, 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 International.

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.

The multi-site study is funded by Boston-based Nephros Therapeutics Inc

[kevin]

Link: http://www.emaxhealth.com/39/3035.html


Why bother fixing something when you can replace it completely?

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Nanotechnology Presents Possibility of Implantable Artificial Kidney
By: Blackwell Publishing on Aug 30 2005 08:21:30

Artificial Kidney
Researchers have developed a human nephron filter (HNF) that would eventually make possible a continuously functioning, wearable or implantable artificial kidney. This study is published in the latest issue of Hemodialysis International.

The HNF is the first application in developing a renal replacement therapy (RRT) to potentially eliminate the need for dialysis or kidney transplantation in end-stage renal disease patients. The HNF utilizes a unique membrane system created through applied nanotechnology. In the ideal RRT device, this technology would be used to mimic the function of natural kidneys, continuously operating, and based on individual patient needs.

No dialysis solution would be used in the device. Operating 12 hours a day, seven days a week, the filtration rate of the HNF is double that of conventional hemodialysis administered three times a week.

"The HNF system, by eliminating dialysate and utilizing a novel membrane system, represents a breakthrough in renal replacement therapy based on the functioning of native kidneys," say researchers. "The enhanced solute removal and wearable design should substantially improve patient outcomes and quality of life."

According to the study, nearly 900,000 patients worldwide suffer from end-stage renal disease and require treatment through dialysis or transplantation. Animal studies using this technology are scheduled to begin in the next 1-2 years with clinical trials to follow subsequently.

This study is published in Hemodialysis International.

Hemodialysis International is published quarterly and contains original papers on clinical and experimental topics related to dialysis in addition to the Annual Dialysis Conference supplement. This journal is a must-have for Nephrologists, Nurses and Technicians worldwide. Quarterly issues of Hemodialysis International are included with your membership to the International Society for Hemodialysis. The journal contains original articles, review articles, commentary and latest news to keep readers completely updated in the field of hemodialysis. Edited by international and multidisciplinary experts, Hemodialysis International disseminates critical information in the field.

Blackwell Publishing is the world's leading society publisher, partnering with more than 600 academic and professional societies. Blackwell publishes over 750 journals annually and, to date has published close to 6,000 text and reference books, across a wide range of academic, medical, and professional subjects.