Predicting Drugs' Harm To Kidneys

A consortium of drug developers, manufacturers, and regulators has shown that seven proteins can better predict drug toxicity in kidneys, a series of papers in Nature Biotechnology explain (2010, 28, 431–494).

The group has been examining markers in animal urine to identify better signals of drugs that are potentially harmful to the kidney.

Scientists hope to identify toxicity to humans before drugs enter clinical trials. The goal is to avoid wasting time, money, and resources on drug candidates that are later tossed because of harmful side effects. Researchers believe they can do this by qualifying biomarkers, such as proteins from certain organs that indicate injury from a drug.

The consortium’s inspection of 23 potential biomarkers of kidney injury identified seven proteins that can be tracked in urine in early-stage drug testing to monitor safety.

Critical Path Initiative, the consortium of drugmakers and regulators, was launched in 2006 by FDA and the European Medicines Agency (EMA) with the hope of collaborating and streamlining the process of identifying potentially toxic drugs before testing them in humans. The task was deemed too large for any one entity, so drug companies are working with FDA and EMA to make it possible.

Consortium members shared their preclinical biomarkers for examination by other members. The proteins found are more sensitive and precise indicators than the current ones, blood-urea nitrogen and serum creatinine. The new biomarkers can eliminate the blind spots left from conventional tests, Merck & Co. safety assessor Frank D. Sistare tells C&EN. The next step, he says, is to perform a clinical study of the identified proteins.

“These findings will impact drug development and likely have an important impact on surveillance for drug toxicity in humans,” says Joseph V. Bonventre, a professor of medicine and health sciences technology at Harvard Medical School who studies the mechanism of kidney injury and repair.

The consortium is also working to find biomarkers for injury to the liver and other organs.