Dr. Mannon explores post-transplant drugs’ effect on kidneys

Kidney transplants save lives, but, all too often, the medications necessary to prevent organ rejection injure the transplanted kidney.

Roslyn “Roz” Mannon, MD, has received a four-year, $500,000 grant from the Veterans Administration to explore a new mouse model she discovered that mimics injury caused by immunosuppressant drugs cyclosporine A and tacrolimus.

Dr. Mannon has a basic science research lab at the Nebraska Western Iowa VA Medical Center in Omaha. On Feb. 1, she joined UNMC as vice chair of academic development and research mentoring and associate chief of research in the UNMC Department of Internal Medicine Division of Nephrology. Dr. Mannon also is a nephrology staff physician at the VA.

Her research goals include learning why kidneys fail after transplantation and ultimately finding a therapy that limits toxicity of a drug. Another goal is to find a way to detect kidney injury without doing biopsies, which are invasive.

In one of the studies, Dr. Mannon and her collaborators will try to replicate kidney injury in her mouse model. About 90 percent of those who receive kidney transplants take one of the agents she is studying in the lab.

“In my career these agents have been revolutionary in helping fight rejection, but they injure the kidney,” Dr. Mannon said. “Over a period of time they cause kidney damage — unintended consequences of agents — and so we’re trying to find new drugs. It would help our field if we could sort out how to detect injury as it’s happening or before and have a helpful intervention. Is it because of the drug or the patient’s makeup?”

Immunosuppressant drugs also are used to treat inflammatory bowel disease, other kidney diseases, and transplants of the heart, liver and lung. They are always cited as a problem, she said.

“We’ve worked around this issue by reducing the drug or replacing it but it’s not been particularly successful,” she said. “At five years after transplant, we start to see attrition — just from kidneys not working adequately. We want to know what’s going on,” she said.

She said acute rejection rates have been reduced to 7% to 10% in the first year after transplantation but that by five years, only 73% of deceased donor kidneys are functioning in their recipients and by 10 years, more than half are lost

She’s submitted scientific papers about the animal model, which are under review.

Currently, she works with Fred Hamel, PhD, professor of internal medicine in the UNMC Division of Diabetes, Endocrine & Metabolism, who also holds an appointment at the VA.

“The VA research program here is phenomenal,” Dr. Mannon said. “I’ve been associated with the VA for my entire career and enjoy caring for veterans.”