Lupus is a systemic autoimmune disease that is complex in genetics and its immunological origins. Renal disease is a leading cause of morbidity and mortality in lupus, particularly among minority women. Although serial renal biopsies may be ideal in closely monitoring the progression of lupus nephritis, it may not be practical or feasible. Hence, the long-term goal of these studies is to identify potential biomarkers that may be of use in monitoring the progression of renal disease in lupus. Using different proteomic approaches, we have uncovered several molecules that appear in the urine during antibody-mediated nephritis. Our completed cross-sectional studies have helped uncover 6 potential biomarker candidates in the urine of mice and patients with lupus. In this proposal, we will study a cohort of lupus patients, 90% of whom are minority individuals, in a longitudinal fashion in order to determine if any of the urinary biomarker candidates might be better at predicting flares, severe histological nephritis, or end stage renal disease, compared to currently used laboratory yardsticks. In addition, we propose to establish the specificity of these biomarkers for lupus nephritis, as well as other causes of proteinuria and nephritis. Given the high incidence of end stage renal disease in lupus, early diagnosis and prompt treatment is absolutely essential. Identification of more predictive biomarkers in the urine of these patients could have a profound impact on the clinical management of lupus nephritis.

Public Health Relevance

Given the high incidence of end stage renal disease in minority women with lupus, early diagnosis and prompt treatment is absolutely essential. Identification of surrogate biomarkers in the urine of these patients could have a profound impact on the clinical management of lupus nephritis. Finally, establishing the pathogenic roles of some of these biomarkers, may pave the way towards better therapy for this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK081872-05
Application #
8539780
Study Section
Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section (HAI)
Program Officer
Flessner, Michael Francis
Project Start
2009-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$422,816
Indirect Cost
$125,062
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Hao, Guiyang; Du, Yong; Zhou, Xin J et al. (2013) Serial non-invasive assessment of antibody induced nephritis in mice using positron emission tomography. PLoS One 8:e57418
Zhang, Song; Ahn, Chul (2013) Sample Size Calculation for Comparing Time-Averaged Responses in K-Group Repeated-Measurement Studies. Comput Stat Data Anal 58:283-291
Wu, Tianfu; Du, Yong; Han, Jie et al. (2013) Urinary angiostatin--a novel putative marker of renal pathology chronicity in lupus nephritis. Mol Cell Proteomics 12:1170-9
Zhang, Song; Ahn, Chul (2012) Sample size calculation for time-averaged differences in the presence of missing data. Contemp Clin Trials 33:550-6
Kiani, Adnan N; Wu, Tianfu; Fang, Hong et al. (2012) Urinary vascular cell adhesion molecule, but not neutrophil gelatinase-associated lipocalin, is associated with lupus nephritis. J Rheumatol 39:1231-7
Zhang, Song; Ahn, Chul (2011) Adding Subjects or Adding Measurements in Repeated Measurement Studies Under Financial Constraints. Stat Biopharm Res 3:54-64
Ahn, Chul; Hu, Fan; Schucany, William R (2011) Sample Size Calculation for Clustered Binary Data with Sign Tests Using Different Weighting Schemes. Stat Biopharm Res 3:65-72
Zhang, Song; Ahn, Chul (2011) How many measurements for time-averaged differences in repeated measurement studies? Contemp Clin Trials 32:412-7
Wu, Tianfu; Fu, Yuyang; Brekken, Deirdre et al. (2010) Urine proteome scans uncover total urinary protease, prostaglandin D synthase, serum amyloid P, and superoxide dismutase as potential markers of lupus nephritis. J Immunol 184:2183-93