Scientists find genetic pathway that could lead to drugs for kidney disease

January 31, 2006

Scientists at the University of California, Santa Barbara have reported a discovery at the cellular level that suggests possibilities for drug therapy for kidney disease.

Over 600,000 people in the U.S. are affected by the inherited kidney disease known as ADPKD, short for autosomal-dominant polycystic kidney disease. In the U.S. this is more than the number of individuals affected by cystic fibrosis, muscular dystrophy, hemophilia, Down's syndrome, and sickle cell anemia combined. The disease is characterized by the proliferation of cysts that eventually debilitate the kidney, causing kidney failure in half of all patients by the time they reach age 50.

Currently no treatment exists to prevent or slow cyst formation, and most ADPKD patients require kidney transplants or life-long dialysis for survival, explained Thomas Weimbs, assistant professor of biology at UCSB and director of the lab that made the discovery, which was reported in the January issue of the journal Developmental Cell.

Kidney cells are lined with small hair-like cilia. The cilia sense fluid flow as urine is passed through the kidney and they send signals to the kidney cells that line the small canals -- called tubules. It is the loss of cilia function that leads to polycystic kidneys.

"With polycystic kidneys, these tubular cells think they have to repair an injury, and they 'repair' by forming lots of cysts," said Weimbs.

The disease is triggered by polycystin-1, a large protein. If it mutates, then the mutation leads to polycystic kidney disease. Even though polycystin-1 was discovered more than a decade ago, its function has remained unknown.

In this study, Weimbs and his colleagues discovered that, under normal conditions, the polycystin-1 keeps certain parts of the cell localized in the cilia and away from the nucleus. These parts of the cell are known as transcription factors. If there is an injury the flow of urine stops, and the transcription factors migrate to the nucleus of the cell, signaling the cell to divide to replace those cells that have been lost. In patients with this disease the repair mechanism is always turned on because the polycystin-1 is defective, or mutated. The discovery of this pathway thus opens the door to possible drug therapy for the disease. This is because the inhibition of any step along this pathway should have beneficial effects. Weimbs and his team are currently capitalizing on these findings by testing drugs to specifically affect components of this novel pathway.
-end-
Note: Weimbs is available at (805) 893-4144, or by e-mail at weimbs@lifesci.ucsb.edu

University of California - Santa Barbara

Related Kidney Disease Articles from Brightsurf:

Waistline matters in kidney disease
Does fat matter in kidney disease? The investigators found that all measures of higher abdominal fat content (including visceral fat, liver fat, or subcutaneous fat) and slower walk times were associated with increased levels of cardiometabolic risk factors in adults with non-dialysis dependent kidney disease.

Reducing urinary protein for patients with rare kidney disease slows kidney decline
New findings show that reducing the amount of protein in the urine of patients with focal segmental glomerulosclerosis can significantly slow declines in kidney function and extend time before patients' kidneys fail.

Antioxidant agent may prevent chronic kidney disease and Parkinson's disease
Researchers from Osaka University developed a novel dietary silicon-based antioxidant agent with renoprotective and neuroprotective effects.

Acute kidney injury and end stage kidney disease in severe COVID-19
Many COVID-19 patients experience hematuria, proteinuria and elevated serum creatinine concentration early in the course of the disease.

Genes tell a story about diabetic kidney disease
Studying Finnish genes leads to unique revelations about the development of a serious complication of diabetes, and informs an ongoing genomic study of a Singaporean cohort as part of Singapore's Diabetes Study in Nephropathy and other Microvascular Complications (DYNAMO).

New study provides insight into chronic kidney disease
Researchers have further analyzed a known signaling pathway they believe brings them one step closer to understanding the complex physiology of patients with chronic kidney disease (CKD), which might provide a path to new treatment options.

Predicting risk of chronic kidney disease
Data from about 5 million people (with and without diabetes) in 28 countries were used to develop equations to help identify people at increased five-year risk of chronic kidney disease, defined as reduced estimated glomerular filtration rate (eGFR).

A healthy diet may help prevent kidney disease
In an analysis of published studies, a healthy dietary pattern was associated with a 30% lower incidence of chronic kidney disease.

Is kidney failure a man's disease?
A new analysis of the ERA-EDTA Registry [1] reveals a striking gender difference in the incidence and prevalence of end-stage renal disease.

Chronic kidney disease: Everyone's concern
850 million people worldwide are affected by kidney disease. This worrying figure was published last June.

Read More: Kidney Disease News and Kidney Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.