Kidney protection


Fuad Ziyadeh with model of kidneys

Photoby Candace diCarlo


Fuad Ziyadeh and kidneys were meant for each other.

“In my first year of medical school, the minute we started studying renal physiology, I was completely sold on nephrology as my specialty,” says the professor of medicine, his eyes flashing with excitement. “I knew I wanted to study it and I didn’t change my mind.”

This summer, Ziyadeh’s passion and years of research paid off when he made a key discovery about how diabetic kidney failure happens and how it might be prevented.

Type II (adult onset) diabetes is the number one cause of kidney failure in the world, accounting for 40 percent of all kidney failure in the United States. Efforts to control the major risk factors for diabetic kidney failure — high blood pressure and high blood sugar (glucose) levels — don’t prevent it. And despite treatment options like dialysis and organ transplantation, the condition is a killer, claiming the lives of 20 percent of its patients annually.

Over the past few years, Ziyadeh has zeroed in on a specific protein as the mechanism through which high glucose levels cause kidney failure. The protein, transforming growth factor-beta (TGF-beta), is instrumental in numerous cell functions, including the healing of tissues after injury. But when TGF-beta is overabundant in kidney cells, the cells produce too much scar tissue, or sclerosis, which clogs up the kidney’s filtering unit and causes failure.

Ziyadeh was the first researcher to pinpoint the link between high glucose and excess TGF-beta, and the first to isolate the growth factor as the culprit in diabetic kidney failure. Working first with kidney tissue culture and most recently with diabetic mice, Ziyadeh administered an antibody to block the action of TGF-beta. As predicted, the antibody prevented sclerosis formation. In the animal trials, the mice receiving the anti-TGF-beta antibody didn’t develop kidney failure even though their glucose levels remained high.

This latest finding, which was published in the July 5 issue of Proceedings of the National Academy of Sciences, points the way to new treatment strategies. According to Ziyadeh, pharmaceutical companies are beginning to seek methods of bringing high TGF-beta levels back down to normal — preventing fatal kidney failure for future generations of diabetics.

Asked why he feels so strongly about kidneys, Ziyadeh whips out a nephrology textbook he co-edited. Right there at the top of the preface is Ziyadeh’s favorite quote from the late renal physiologist Homer Smith:

“Superficially, it might be said that the function of the kidneys is to make urine. But in a more considered view, one can say that the kidneys make the stuff of philosophy itself.”

So we just have to ask: How are kidneys philosophic?

“Kidneys are very intelligent organs,” Ziyadeh says. “They have a way of reasoning what to do in the face of any change in the composition of the body fluids. You would think that they are working with some teleologic mindset.”

Originally published on August 31, 2000