Kidney disease treatment may be on the way
By Penny Stern, MD
NEW YORK, Jan 17 (Reuters Health) -- A new drug may be a promising treatment for one type of polycystic kidney disease (PKD), a relatively common genetic disorder that causes multiple cysts to form on the kidney, leading to life-threatening complications and kidney failure.
In a study in mice with a similar disease, a drug known as EKI-785 reduced the number of cysts, improved kidney function, and at least doubled the animals' lifespan, according to a report in the January issue of Kidney International.
"These findings are exciting because they represent a completely new approach to specifically treat a disease which is common and often debilitating," said principal investigator Dr. Ellis Avner of Rainbow Babies and Children's Hospital in Cleveland, Ohio, in an interview with Reuters Health.
EKI-785 blocks a cell receptor for epidermal growth factor (EGFR), a naturally occurring growth factor. It is thought that the kidney disease occurs due to overstimulation of the receptor, causing cysts to form. The cysts can be tiny or grow to the size of a football, ultimately causing kidney failure.
"We have identified a critical role for the abnormal expression of a... growth factor receptor (called) EGFR in this process," Avner said. "This abnormality drives the abnormal proliferation of kidney cells in PKD," he continued.
Avner and colleagues injected the EGFR-inhibitor into the mice with a form of the disease known as autosomal recessive PKD. This form of the disease is less common and often fatal in the first month of life, according to the Polycystic Kidney Research Foundation, which funded the study in conjunction with Wyeth-Ayerst, the drug's manufacturer.
When this inhibitor was injected into the study mice, the investigators found that "treated animals had decreased mortality, decreased kidney cystic abnormalities, and markedly increased kidney function when compared to untreated animals," Avner told Reuters Health. Furthermore, there was "minimal toxicity," he said.
Clinical trials of the drug will soon begin in human patients, Avner said.
"The exact timing will depend on the completion of exhaustive toxicology studies, which are a prerequisite to clinical trials. I would hope that we will be ready to initiate such trials within the next 12 to 16 months," he said.
At present, there are no specific treatments to slow or halt the growth of the cysts in people with PKD, Avner said.
Dr. Jared Grantham, of the University of Kansas Medical Center in Kansas City and co-founder of the Polycystic Kidney Research Foundation, points out in an accompanying commentary that "the economic and emotional costs of polycystic kidney disease are enormous."
The study is "a giant leap forward" and the findings "have great potential for the treatment of children with the rapidly progressive form of polycystic kidney disease, and perhaps those with (other types) of (PKD) as well," he writes.
SOURCE: Kidney International 2000;57:33-40, 339-340. |
