Background: Adiponectin is an adipocyte-derived cytokine that has anti-inflammatory properties. A preliminary proteomic evaluation of urine for biomarkers of systemic lupus erythematosus (SLE) nephritis demonstrated high levels of adiponectin in SLE urine. This prompted investigation of adiponectin expression in human SLE.
Methods: Adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) in the urine and plasma of a clinically well-characterized SLE cohort, with renal and nonrenal SLE being followed in a prospective longitudinal study to identify risk factors for SLE flare. Renal adiponectin expression was assessed by immunohistochemical analysis of kidney biopsies from SLE nephritis patients.
Results: Cross-sectional testing showed that plasma adiponectin levels were higher in patients with renal SLE flare than normal controls or patients with nonrenal SLE flare, after accounting for race and body mass index. Urine adiponectin levels increased significantly with renal flare, but not nonrenal SLE flare. Longitudinal testing revealed that the urine adiponectin increase began in the 2 months prior to renal flare. Urine adiponectin correlated with plasma levels and magnitude of proteinuria, and to a lesser extent serum creatinine. Plasma adiponectin levels were independent of renal function and proteinuria. In kidney biopsies, adiponectin was found on endothelial surfaces in normal and SLE kidneys, and on podocytes and in the tubules of SLE kidneys.
Conclusion: Plasma adiponectin levels are increased in patients with renal SLE compared to healthy controls and patients with nonrenal SLE. During renal but not nonrenal SLE flare, urine adiponectin levels increase significantly. Urine adiponectin may be a biomarker of renal SLE flare.