Ellen Cody, MD
2020 Recipient of the Gary S. Gilkeson Career Development Award
Cincinnati Children's Hospital Medical Center
Title of Project: Assessing Performance of Urinary Biomarkers, Renal Activity Index for Lupus (RAIL)
Mentor: Hermine I. Brunner, M.D. M.Sc. M.B.A, Professor of Pediatrics, Director, Division of Rheumatology, Scientific Director Pediatric Rheumatology Collaborative Study Group
Project Summary: Systemic Lupus Erythematosus (SLE), particularly when involving the kidney (lupus nephritis -LN), can cause devastating illness, including end-stage renal disease requiring dialysis or kidney transplant. Poor prognosis is in part due to lack of available laboratory and clinical tests to diagnose LN early and evaluate response to therapy.
Previously described and initially validated are a panel of LN-biomarkers, i.e. NGAL, MCP-1, Kim-1, ceruloplasmin, adiponectin, and hemopexin, developed by collaborators of the applicant. Based on the urine concentrations of these biomarkers, Renal Activity Index for Lupus (RAIL) was developed, where higher RAIL scores reflect more kidney inflammation. The published research showed that the RAIL score (a) has 94% accuracy to discriminate high from low levels of kidney inflammation as detected by kidney biopsy; (b) anticipates the clinically observed course of LN at least 3 months earlier than when using current measures; (c) helps to distinguish LN activity from LN damage non-invasively; and (d) pilot studies suggest that RAIL scores can be used to refine the dosing of current LN therapies in individual patients.
Over the next 1-2 years we will aim to define changes in the RAIL score that reflect response or failure to induction therapy for LN, respectively; delineate RAIL scores expected with the presence of active/controlled/absent LN; and determine if RAIL scores can predict responders versus non-responders through initial therapy.