Glycosphingolipids as Therapeutic Targets and Biomarkers of Lupus Nephritis
Abstract
This application directly addresses the Peer Reviewed Medical Research Program Topic Area of Lupus. Lupus is a chronic autoimmune disease. The most severe complication of lupus is kidney disease, which affects up to two-thirds of lupus patients and is associated with high morbidity and mortality. Lupus nephritis shares features with other chronic kidney diseases including elevation of lipids called glycosphingolipids (GSLs) in the urine and kidney. GSLs are highly enriched in the kidney and can play a role in the progression of kidney disease. We were the first to demonstrate that these lipids are elevated in the urine and kidney of lupus patients with nephritis. Additional preliminary data indicate that urine GSLs are significantly higher in the urine of lupus nephritis patients who fail therapy. We believe that reducing the levels of GSLs will slow the development of kidney disease. To test this, we propose to reduce GSL levels in mice that develop lupus and determine if disease improves. In addition, we believe that GSL levels in urine can be used to identify patients who will fail therapy as well as patients who may flare and/or develop worse kidney disease. To test this, GSL levels will be measured in the urine of lupus patients before they started therapy and at 3, 6, and 12 months after starting therapy. Three Food and Drug Administration-approved drugs are available that can alter the levels of GSLs. Therefore, the results obtained from our novel studies could be rapidly translated to the Veteran population. Additionally, we propose an innovative approach for analyzing urine GSL levels that can be easily used to identify patients that respond (or will fail to respond) to therapy earlier than currently used measures. There are more than 600,000 Veterans with chronic kidney diseases being treated in the Department of Veterans Affairs (VA) system. The proposed studies will lead to the identification of additional targets for treatment and markers of lupus nephritis (and potentially other kidney diseases) and earlier intervention, thus reducing health disparities and relieving the burden of increased healthcare costs for Veterans with chronic kidney disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610640
Entities
People
- Tamara K Nowling
Organizations
- Medical University of South Carolina
- United States Army