Patient-Oriented, Translational Research: Research Article Am J Nephrol 2021;52:559–571 Prognostic and Diagnostic Values of Novel Serum and Urine Biomarkers in Lupus Nephritis: A Systematic Review Massimo Radin a Paolo Miraglia a, b Alice Barinotti a, b Roberta Fenoglio c Dario Roccatello a, c Savino Sciascia a, c a Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Aosta Valley Network for Rare Diseases, S. Giovanni Bosco Hospital, University of Turin, Turin, Italy; b Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, Turin, Italy; c Department of Clinical and Biological Sciences, Nephrology and Dialysis, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy Received: March 31, 2021 Accepted: June 14, 2021 Published online: August 13, 2021 Correspondence to: Savino Sciascia, savino.sciascia @unito.it © 2021 S. Karger AG, Basel karger@karger.com www.karger.com/ajn DOI: 10.1159/000517852 Keywords Lupus nephritis · Systemic lupus erythematosus · Biomarker · Urinary · Serological · Systematic review Abstract Introduction: While renal biopsy remains the gold standard for diagnosing lupus nephritis (LN), the prognostic and diag- nostic role of non-invasive biomarkers for LN is currently de- bated. Methods: 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. Results: 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 stud- ies (34%) tested their population only with urinary biomark- ers, and 12 (14%) investigated the presence of both. Out- come measures to assess the clinical utility of the analyzed biomarkers were heterogeneous, including up to 21 differ- ent 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 che- moattractant protein, urinary adiponectin, and urinary vas- cular cell adhesion protein 1. Discussion/Conclusion: 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 appli- cability in current clinical practice. With the kidney biopsy still representing the gold standard, future efforts should fo- cus on harmonizing study inclusion criteria and outcomes, particularly in clinical trials, in order to improve comparabil- ity and facilitate the implementations of available biomark- ers into the daily practice. © 2021 S. Karger AG, Basel Significance Statement While kidney biopsy is crucial for lupus nephritis (LN) diagnosis, the identification of one or more non-invasive biomarkers (serological or urinary) is highly needed. Po- tentially, the study of novel biomarkers may be useful to provide further information on LN: mainly the degree of