Nicholas Li, MD, PhD
2020 Recipient of the Gary S. Gilkeson Career Development Award
The Ohio State University
Title of Project: Characterization of urine complement proteins as biomarkers of lupus nephritis activity
Mentor: Brad H. Rovin, MD, FACP, FASN, Director of Nephrology, Professor of Medicine and Pathology, The Lee A. Hebert Professor of Nephrology, Director, the Ohio State University, Clinical Management Organization, Ohio State University Wexner Medical Center
Project Summary: The complement system is a mechanism through which the body protects itself from infection and injury, and is important in cleaning up molecules in the circulation or tissues that may cause harm. People who lack certain complement components can develop lupus and often lupus with kidney disease (lupus nephritis, LN), suggesting a role for complement in protection from autoimmunity. However, complement proteins are generally found in the kidney of patients with LN, and when these components are blocked in animal models of LN, the disease is made much better.
There are now complement inhibitors that have been developed for human use that are being tested in several kidney diseases, but have not been used in LN. One important reason for this is that we don’t have a good way to assess the level of complement activation in an individual patient’s kidneys at the time of LN diagnosis. Knowing this would help determine if a complement drug would be a good fit for that patient.
We have developed ways to measure the components of the complement system that can injure the kidney in the urine of patients with LN. We believe that these components reflect kidney complement activity and can be used as markers to choose patients for complement therapy.
This project will test this idea. If successful the results will provide a way to match lupus patients with a treatment that directly blocks the pathway to injury of the kidney. We expect this will result in improved responses to treatment with far fewer side effects than the usual treatments used for LN.