Supplementary Material for: Prognostic and Diagnostic Values of Novel Serum and Urine Biomarkers in Lupus Nephritis: A Systematic Review

<b><i>Introduction:</i></b> While renal biopsy remains the gold standard for diagnosing lupus nephritis (LN), the prognostic and diagnostic role of non-invasive biomarkers for LN is currently debated. <b><i>Methods:</i></b> Available studies published in last 5 years (2015–2020) assessing the diagnostic and prognostic value of urinary and/or serological biomarkers in subjects with LN were analyzed in this systematic review. <b><i>Results:</i></b> Eighty-five studies were included (comprehending 13,496 patients with systemic lupus erythematosus [SLE], 8,872 LN, 487 pediatric LN, 3,977 SLE but no LN, 160 pediatric SLE but no LN and 7,679 controls). Most of the studies were cross-sectional (62; 73%), while 14 (17%) were prospective. In sixty studies (71%), the diagnosis of LN was biopsy-confirmed. Forty-four out of 85 (52%) investigated only serological biomarkers, 29 studies (34%) tested their population only with urinary biomarkers, and 12 (14%) investigated the presence of both. Outcome measures to assess the clinical utility of the analyzed biomarkers were heterogeneous, including up to 21 different activity scores, with the SLEDAI (in 60%) being the most used. Despite some heterogeneity, promising results have been shown for biomarkers such as urinary monocyte chemoattractant protein, urinary adiponectin, and urinary vascular cell adhesion protein 1. <b><i>Discussion/Conclusion:</i></b> While serum and urine biomarkers have the potential to improve diagnostic and prognostic pathways in patients with LN, the vast heterogeneity across studies severely limits their applicability in current clinical practice. With the kidney biopsy still representing the gold standard, future efforts should focus on harmonizing study inclusion criteria and outcomes, particularly in clinical trials, in order to improve comparability and facilitate the implementations of available biomarkers into the daily practice.