Researchers in the US have managed to combine live kidney cells and a modified dialysis machine to produce a "bio-artificial kidney" that works much more like the real thing. This new form of "tissue engineering" has the potential to help save thousands of lives by keeping patients struck by acute kidney failure alive long enough for their own kidneys to heal.
The work at the Department of Internal Medicine at the University of Michigan is headed by Dr H David Humes. He found that the artificial kidney provided half the functional capacity of a natural kidney in dogs with impaired kidneys.
The bio-artificial kidney replaces many of the missing functions of the natural organ including the ability to produce "metabolites", for example substances important to the immune system, explained the research team's spokesman, Mr Dan Cutler of the University of Michigan.
"The patient in acute renal failure succumbs to infections due to the fact that with the failure of the kidney comes the failure to produce these metabolites," Mr Cutler explained.
Almost a million people fall victim to acute renal failure each year in the US and many thousands here. These cases typically require a 10-day stay in an hospital intensive care unit and half of these patients don't survive.
Kidneys fail in two ways, Mr Cutler said: chronic failure in which the kidney is lost and the patient can only survive on kidney hemodialysis, and acute failure, brought on by infection, surgery and other "insults" to the organ. You can survive acute failure provided the doctors can keep you alive long enough for kidney function to return.
Dr Humes is a nephrologist and had a particular interest in the development of acute kidney failure, Mr Cutler said. "He realised that there was a way that these kidneys were healing themselves," he said, and Dr Humes decided to locate which cells were important to this process.
His search led to cells in the "renal proximal tubule", the tubelike structures found in the kidney which are lined with these cells and through which the organ passes fluids for filtration. He isolated "progenitor" cells which develop to become renal tubule cells and grew them for study in the laboratory. This work also provided information about what these cells did and what part they played in normal kidney function.
The kidney is usually described as a filter, removing urea and excess water for disposal via the bladder. However, it provides many more services. It reabsorbs valuable molecules that are recycled back into the bloodstream, preventing their loss. It produces metabolites important to the immune system and others that control nutritional status, for example for the activation of vitamin D.
Dialysis can provide the filtration but not the other aspects. The new bio-artificial kidney first does the heavy filtration and then the live kidney cells in the device both reabsorb useful substances and contribute their usual metabolites. All of the cell integration and development work was done in the university's laboratory. Dr Humes's team adopted the physiology of the kidney, structures which are also seen in dialysis machines. Very thin hollow but porous tubes that look much like fishing line to the unaided eye are first coated inside with an "adhesion molecule". Renal tubule cells are then introduced and these stick to the surface to form a layer a single cell thick.
The ultra-filtered fluid coming from dialysis is then passed along these cell-lined tubes and the cells begin to function as they do in the natural organ, taking up and saving nutrients and releasing their normal substances.
The research team could monitor how well the bio-artificial organ was doing by measuring various metabolites. They were also able to show that the cells survived quite well and there was very little cell release from the tube surface.
The research group is now seeking FDA approval for human trials to begin this autumn. "The ultimate goal is to take this and develop an implantable form," Mr Cutler said.
This is obviously something for the future. Even as it is, the new bio-artificial kidney holds much promise for the treatment of acute kidney failure and the potential to save many lives if clinical trials prove successful.
