Urine Chemokines as Biomarkers of Human Systemic Lupus... : Journal of the American Society of Nephrology (original) (raw)

Clinical Nephrology

Urine Chemokines as Biomarkers of Human Systemic Lupus Erythematosus Activity

Rovin, Brad H.*; Song, Huijuan*; Birmingham, Dan J.*; Hebert, Lee A.*; Yu, Chack Yung†; Nagaraja, Haikady N.‡

*Department of Medicine and the Dorothy M. Davis Heart and Lung Research Institute, Ohio State University College of Medicine and Public Health; †Columbus Children’s Hospital and Research Institute; and ‡Department of Statistics, Ohio State University, Columbus, Ohio

Address correspondence to: Dr. Brad H. Rovin, Ohio State University, Nephrology Division, N210 Means Hall, 1654 Upham Drive, Columbus, Ohio 43210. Phone: 614-293-4997; Fax: 614-293-3073; E-mail: [email protected]

Accepted November 5, 2004

Received August 11, 2004

Abstract

The purpose of this study was to evaluate urine monocyte chemoattractant protein-1 (MCP-1) and IL-8 as biomarkers of SLE flare. Urine was collected every 2 mo from patients who were followed prospectively in the Ohio SLE Study. Renal and nonrenal flares were identified and MCP-1 and IL-8 were measured by specific ELISA in samples that were collected at flare. When available, MCP-1 and IL-8 were also measured in urine samples before and after flare. For comparison, MCP-1 and IL-8 were measured in the urine of healthy individuals and in renal and nonrenal SLE patients with stable disease activity (disease controls). Most patients were receiving maintenance immunosuppressive therapy before flare. At renal flare, mean urine MCP-1 (uMCP-1) was significantly greater than uMCP-1 at nonrenal flare and from healthy volunteers and renal disease controls. The level of uMCP-1 correlated with the increase in proteinuria at flare and was higher in patients with proliferative glomerulonephritis and in patients with impaired renal function. Urine MCP-1 was increased beginning 2 to 4 mo before flare. Patients who responded to therapy showed a slow decline in uMCP-1 over several months, whereas nonresponders had persistently high uMCP-1. In contrast, uIL-8 did not change with disease activity and was not elevated at renal or nonrenal flare compared with disease controls. In conclusion, uMCP-1 but not uIL-8 is a sensitive and specific biomarker of renal SLE flare and its severity, even in patients who receive significant immunosuppressive therapy. Persistently elevated uMCP-1 after treatment may indicate ongoing kidney injury that may adversely affect renal prognosis.