Growth Factor May Protect Against Kidney Failure

Newswise — A natural molecule called hepatic growth factor (HGF) offers a promising new target for gene therapies to prevent and treat acute renal failure, reports a study in the January Journal of the American Society of Nephrology.

Acute renal failure occurs commonly in intensive care units following major surgery and other events and currently has a mortality of about 50%. It is a major cause of death in seriously ill patients.

A research team led by Dr. Nathalie M. Fiaschi-Taesch of University of Pittsburgh School of Medicine developed genetically engineered mice to express higher-than-normal levels of HGF or another natural factor called parathyroid hormone-related protein (PTHrP). Both groups of mice developed normal kidneys. This allowed the researchers to see how the high levels of HGF or PTHrP would affect recovery after blood flow to the kidney was temporarily interrupted.

In normal, "wild-type" mice, the injury caused by lack of blood supply resulted in sharply reduced kidney function, which worsened over time. In contrast, in animals genetically engineered to express high levels of HGF, the injury caused a much lower level of kidney damage. Two days later, kidney function had almost completely returned to normal in the high-HGF mice. Mice overexpressing HGF were also more likely to survive after kidney injury.

Acute renal failure occurs because of renal tubule cell death. Examination under the microscope showed the reason why kidney function was preserved in high-HGF mice. The high HGF levels seemed to have a protective effect on renal tubule cells, which play a key role in kidney's ability to produce urine. Compared with wild-type mice, the rate of renal tubule cell development was four times faster in high-HGF mice, while the rate of renal tubule cell death was three times slower.

The researchers performed similar experiments in genetically engineered high-PTHrP mice. Surprisingly, however, the high levels of PTHrP had no protective effect on kidney function or on renal tubule cells.

New treatments are needed to reduce the rate of acute renal failure and enhance recovery in patients who suffer injury to the kidneys. Previous laboratory studies had suggested that HGF or PTHrP might have such protective effects. The fact that the kidneys developed normally in high-HGF and high-PTHrP mice is an important step forward in assessing the protective effects of these factors against kidney cell damage.

High levels of HGF have the potential to protect against the development of renal failure after kidney injury, these initial experiments suggest. Hepatic growth factor may be a key part of future attempts to develop gene therapy approaches to acute renal failure. The next challenge will be finding some way of targeting high HGF levels directly to the renal tubule cells.

Journal of the American Society of NephrologyVolume 14, Issue 12January 2004