Developing a Lupus Nephritis urinary biomarker panel in children for use in a clinical trial

Background: Juvenile-onset systemic lupus erythematosus (JSLE) is a rare, severe multisystem autoimmune disease affecting the kidney (Lupus Nephritis, LN) in up to 80% of children. Numerous individual urinary biomarkers have previously been investigated. No individual biomarker has achieved ‘excellence’ in differentiating active from inactive LN. Aims: (1) To assess performance of traditional clinical biomarkers for LN monitoring and prediction of LN outcomes. (2) To select biomarkers warranting assessment in a ‘LN biomarker panel’; to cross-sectionally assess if combining novel/traditional biomarkers improves active LN identification. (3) To validate the optimal UK LN biomarkers within independent, ethnically distinct JSLE cohorts. (4) To longitudinally assess if urine biomarkers predict LN flare/remission. (5) To streamline methods for LN urine biomarker panel quantification. Methods: Clinical data and urine samples from UK, United States (US) and South African (SA) JSLE patients were utilised within cross-sectional and longitudinal studies assessing combinations of novel urine/traditional clinical biomarkers. A custom LN biomarker panel multiplex assay was developed/validated in collaboration with Merck Millipore. Results: 37% of UK patients displayed active LN as an initial presenting feature, with a further 17% developing LN after a median of 2.04 years [IQR 0.8-3.7]. ACR score (>5) and C3 levels (