Journal Article

Diagnostic test accuracy of novel biomarkers for lupus nephritis—An overview of systematic reviews

Lucas, Ana Cyra dos Santos, Mori, Bruno, Guimarães, Juliana de Andrade Rebouças, Barcellos, José Fernando Marques, Furtado, Silvania da Conceição

2022

Overview

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan inflammatory involvement and a mortality rate that is 2.6-fold higher than individuals of the same age and sex in the general population. Approximately 50% of patients with SLE develop renal impairment (lupus nephritis). Delayed diagnosis of lupus nephritis is associated with a higher risk of progression to end-stage renal disease, the need for replacement therapy, and mortality. The initial clinical manifestations of lupus nephritis are often discrete or absent and are usually detected through complementary tests. Although widely used in clinical practice, their accuracy is limited. A great scientific effort has been exerted towards searching for new, more sensitive, and specific biomarkers in recent years. Some systematic reviews have individually evaluated new serum and urinary biomarkers tested in patients with lupus nephritis. This overview aimed to summarize systematic reviews on the accuracy of novel serum and urinary biomarkers for diagnosing lupus nephritis in patients with SLE, discussing how our results can guide the clinical management of the disease and the direction of research in this area. The research question is \"What is the accuracy of the new serum and urinary biomarkers studied for the diagnosis of LN in patients with SLE?\". We searched for systematic reviews of observational studies evaluating the diagnostic accuracy of new serum or urinary biomarkers of lupus nephritis. The following databases were included: PubMed, EMBASE, BIREME/LILACS, Scopus, Web of Science, and Cochrane, including gray literature found via Google Scholar and PROQUEST. Two authors assessed the reviews for inclusion, data extraction, and assessment of the risk of bias (ROBIS tool). Ten SRs on the diagnostic accuracy of new serum and urinary BMs in LN were selected. The SRs evaluated 7 distinct BMs: (a) antibodies (anti-Sm, anti-RNP, and anti-C1q), (b) cytokines (TWEAK and MCP-1), (c) a chemokine (IP-10), and (d) an acute phase glycoprotein (NGAL), in a total of 20 review arms (9 that analyzed serum BMs, and 12 that analyzed BMs in urine). The population evaluated in the primary studies was predominantly adults. Two SRs included strictly adults, 5 reviews also included studies in the paediatric population, and 4 did not report the age groups. The results of the evaluation with the ROBIS tool showed that most of the reviews had a low overall risk of bias. There are 10 SRs of evidence relating to the diagnostic accuracy of serum and urinary biomarkers for lupus nephritis. Among the BMs evaluated, anti-C1q, urinary MCP-1, TWEAK, and NGAL stood out, highlighting the need for additional research, especially on LN diagnostic panels, and attempting to address methodological issues within diagnostic accuracy research. This would allow for a better understanding of their usefulness and possibly validate their clinical use in the future.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Accuracy / Adults / Age groups / Analysis / Antibodies / Autoimmune diseases / Bias / Biological markers / Biology and Life Sciences / Biomarkers / Biopsy / Chemokines / Chronic conditions / Creatinine / Cytokines / Diagnosis / Diagnostic tests / End-stage renal disease / Evaluation / Glycoproteins / Health risks / IP-10 protein / Kidney diseases / Literature reviews / Lupus / Lupus nephritis / Medical diagnosis / Medical prognosis / Medical tests / Medicine and Health Sciences / Microscopy / Monocyte chemoattractant protein 1 / Mortality / Nephritis / Observational studies / Patients / Population studies / Proteins / Remission (Medicine) / Renal function / Research and Analysis Methods / Rheumatology / Risk assessment / Systemic lupus erythematosus / Urinalysis / Urine