Lupus Nephritis (LN) is a complication of lupus and is associated with immense cost, suffering, and mortality. The criterion standard for the diagnosis and monitoring of LN is a kidney biopsy. The non-invasive traditional measures of LN (LN-TM) currently used to monitor LN have limited responsiveness to change. This prohibits the verification of the effectiveness of LN therapies early, which hinders both clinical care and clinical trial conduct. Recently, we discovered and initially validated promising LN biomarkers (a.k.a. the LN-Panel) that accurately reflect LN activity &chronicity as seen on kidney biopsy, and can forecast LN flares. There remains an important unknown, i.e. whether the LN-Panel can serve as an early measure of LN improvement. The objective of this application is to validate the LN-Panel as a set of highly responsive biomarkers that reliably and rapidly detect response to LN therapy. The principal hypothesis to be tested is that the LN-Panel is a group of combinatorial biomarkers that surpasses LN-TM in anticipating remission of LN, in both children and adults. Supported by 6 NIH-funded Centers of Excellence, we will use banked samples, and information from ongoing medication studies to pursue the following specific aims:
Aim 1 : To investigate the ability of the LN-Panel to prognosticate the therapeutic response of children with LN.
Aim 2 : To delineate the impact of patient age, gender and ethnicity on the measurement properties of the LN- Panel, with focus on capturing improvement of LN.
Aim 3 : To explore the importance of medication choice on the capability of the LN-Panel to serve as an early measure of LN improvement. This study is innovative as essential unknowns about highly promising candidate biomarkers for LN will be elucidated. We expect that this large scale validation study will provide critical information that is required for the biomarker qualification process of the L-Panel. Our findings will ultimately allow for the testing of novel medications for LN, in both children and adults with shorter clinical trials, at markedly lower cost and less risk to the patients. Furthermore, we anticipate that the LN-Panel will improve the monitoring of LN in daily clinical practice, allowing LN care to be tailored to the patients'needs in an effort to improve their long-term prognosis.

Public Health Relevance

Our research is poised to have a major impact on the U.S. public health, because LN constitutes the 3rd most common cause for renal replacement therapy in the U.S., and results in health care cost of >$361 million annually. Adults with LN have an 8x higher mortality and children with LN an even 19x higher risk of dying compared to the general population. Our study is essential for bringing novel LN biomarkers to the patients'bedside, for improved LN surveillance and testing of life-saving drugs to improve LN long-term outcomes.

National Institute of Health (NIH)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAR1)
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Witter, James
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