Protein may provide a powerful new therapeutic tool for fighting kidney failure

Feb 16 2005

Columbia University Medical Center researchers have identified a protein that may provide a powerful new therapeutic tool for fighting kidney failure.

The research, which is published in the March issue of the Journal of Clinical Investigation, shows that injection of a protein, known as Ngal, can protect mice from renal failure, suggesting its great potential as a therapeutic tool for humans.

Kidney failure is a significant risk for patients undergoing cardiopulmonary bypass surgery, radiologic testing, antibiotic therapy or in patients suffering from severe infections. More than 80 percent of patients with postoperative acute renal failure die.

The study also shows that the protein is highly accumulated in blood, urine and kidney tissue at the onset of acute renal failure, making it an effective marker for diagnosing kidney failure in its initial stages.

"We found that although Ngal exists in high amounts early in failing kidneys, it is still produced too late to prevent the damage," said Jonathan Barasch, M.D., Ph.D., assistant professor of Medicine at Columbia University College of Physicians and Surgeons and the principal investigator on the study. "But if we inject the protein earlier in the process, such as when a patient is starting bypass surgery or using some antibiotics, our study suggests that Ngal can prevent damage from occurring."

Ngal was initially discovered by Dr. Barasch and his colleagues to induce embryonic cells to form kidney tubules.

"When Dr. Devarajan of Cincinnati Children's Hospital identified Ngal in a screen for genes expressed in damaged kidneys, we decided to join forces, because there were theoretical reasons why creation of embryonic kidneys and repair of adult kidneys should be stimulated by the same molecule," said Kiyoshi Mori, M.D., PhD., a post-doctoral research fellow.

The two groups independently showed that Ngal is a sensitive marker of renal failure and after extensive studies with mice, the two independently found that Ngal was protective.

"Given the fact that Ngal expression is conserved in mice, rats, and human kidneys after damage, we are hopeful that the protein will be protective in humans," said Dr. Barasch.

Ngal will be ready for initial human trials after one further confirmation in mouse models.

The study is the result of a collaboration between Columbia University Medical Center's departments of Medicine (Kiyoshi Mori, Cheryl Kunis and Jonathan Barasch), Anesthesiology (H. Thomas Lee), and Pathology (Vivette D'Agati), as well as researchers at Cincinnati Children's Hospital (Jaya Mishra, Prasad Devarajan), and Kyoto University (Masashi Mukoyama).