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

Laurie Barclay, MD

November 04, 2004

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 earlyefficacy 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

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