Biomarkers of Lupus Nephritis Histopathology: Where Do We Stand?

Objective Lupus nephritis (LN) is characterized by a variable disease course, necessitating continuous monitoring. There is an urgent need to identify noninvasive biomarkers. By reviewing and critically assessing the quality of existing studies on LN biomarkers correlating with histopathology, we here explore the challenges in promoting their use in clinical practice and identify promising candidates for future validation. Methods A systematic literature search was conducted, including studies on adult patients with biopsy-proven LN published between 2012 and 2024. The search focused on studies demonstrating correlations between biomarkers and histologic findings, particularly the National Institutes of Health activity and chronicity indices, the International Society of Nephrology/Renal Pathology Society histologic classes, and specific active and chronic lesions. The quality of selected articles was assessed by a multidisciplinary panel of experts using a standardized scoring system. Results Ninety-three articles investigating the potential utility of >100 biomarkers were selected. In quality assessment, 68% of the articles were weak or very weak (score <5, scale 2-9). From the remaining articles (adequate or robust) we identified five biomarkers with a potential for implementation in clinical practice: transforming growth factor beta 1, pentraxin-3, (soluble) CD163, CD11b, and interleukin-16. Conclusion The methodologic heterogeneity across studies and the overall moderate score of the quality of the articles represent obstacles to the implementation of new biomarkers into clinical practice. The LN working group advocates further research on selected biomarkers that demonstrated good capacity to reflect specific histopathologic features outperforming traditional tests. At present, the choice of biomarkers that perform to these standards is very limited.