Kidney involvement in human SLE is common and usually severe. Although current immunosuppressive drugs can control renal SLE, therapy would be more effective with less toxicity if the onset, severity, or responsiveness of lupus renal flares could be predicted, and treatment modified accordingly. Presently there are no clinically validated biomarkers that can be used to reliably monitor SLE renal activity throughout the flare cycle. However, recent data from this laboratory show that levels of the chemokine monocyte chemoattractant protein-1 (MCP-1) increase significantly in the urine of patients having a renal flare, and appear to reflect disease activity and severity. It was thus postulated that urine MCP-1 (uMCP-1) is a lupus nephritis biomarker that reflects the level of kidney inflammation, and that can be used to predict impending flare, flare severity, and flare prognosis. The purpose of this investigation is to validate uMCP-1 as a biomarker of SLE nephritis flare cycles and renal inflammation. The study goals will be addressed through two Specific Aims that utilize the Ohio SLE Study (OSS) database and specimen bank, developed at Ohio State University. The OSS contains clinical information and serial urine samples from a cohort of well-characterized SLE patients followed prospectively every 2 months over several years.
In Aim 1, uMCP-1 levels will be measured by ELISA in samples obtained before, during, and after SLE renal flares, and correlated to clinical course. The sensitivity and specificity of uMCP-1 as a predictor of flare onset, severity, and response to therapy will be calculated, and the interaction of uMCP-1 with traditional clinical markers of SLE will be assessed.
In Aim 2, uMCP-1 measured at kidney biopsy will be correlated with infiltrating renal leukocytes, glomerular crescents, glomerulosclerosis, interstitial fibrosis, and tubular atrophy, to determine whether uMCP-1 levels reflect specific renal lesions found in SLE nephritis that can affect kidney survival. To test whether uMCP-1 correlates better with renal inflammation or fibrosis, the strength of the association of uMCP-1 and renal inflammation will be compared to the strength of the association of uMCP-1 and renal fibrosis. In summary, this project is expected to demonstrate that uMCP-1 is a valid biomarker of lupus nephritis and its flare, and can be used to facilitate treatment decisions.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Pathobiology of Kidney Disease Study Section (PBKD)
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Flessner, Michael Francis
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Ohio State University
Internal Medicine/Medicine
Schools of Medicine
United States
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Hebert, Lee A; Parikh, Samir; Prosek, Jason et al. (2013) Differential diagnosis of glomerular disease: a systematic and inclusive approach. Am J Nephrol 38:253-66
Shapiro, John P; Biswas, Sabyasachi; Merchant, Anand S et al. (2012) A quantitative proteomic workflow for characterization of frozen clinical biopsies: laser capture microdissection coupled with label-free mass spectrometry. J Proteomics 77:433-40
Brunner, Hermine I; Bennett, Michael R; Mina, Rina et al. (2012) Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis. Arthritis Rheum 64:2687-97
Zhang, Xiaolan; Nagaraja, Haikady N; Nadasdy, Tibor et al. (2012) A composite urine biomarker reflects interstitial inflammation in lupus nephritis kidney biopsies. Kidney Int 81:401-6
Winoto, J; Song, H; Hines, C et al. (2011) Cytochrome P450 polymorphisms and the response of lupus nephritis to cyclophosphamide therapy. Clin Nephrol 75:451-7
Budu-Grajdeanu, Paula; Schugart, Richard C; Friedman, Avner et al. (2010) Mathematical framework for human SLE Nephritis: disease dynamics and urine biomarkers. Theor Biol Med Model 7:14
Birmingham, D J; Irshaid, F; Nagaraja, H N et al. (2010) The complex nature of serum C3 and C4 as biomarkers of lupus renal flare. Lupus 19:1272-80
Zhang, Xiaolan; Rovin, Brad H (2010) Hepcidin expression by human monocytes in response to adhesion and pro-inflammatory cytokines. Biochim Biophys Acta 1800:1262-7
Rovin, Brad H; Zhang, Xiaolan (2009) Biomarkers for lupus nephritis: the quest continues. Clin J Am Soc Nephrol 4:1858-65
Fine, Derek M; Ziegenbein, Martina; Petri, Michelle et al. (2009) A prospective study of protein excretion using short-interval timed urine collections in patients with lupus nephritis. Kidney Int 76:1284-8

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