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Objectives In this study, we aimed to investigate serum suPAR levels in relation to lupus nephritis (LN), including activity and chronicity features in diagnostic and per-protocol repeat kidney biopsies.Methods Serum levels of suPAR from patients with LN from the Cliniques Universitaires Saint-Luc, Brussels, Belgium (N=21) and the Karolinska University hospital, Stockholm, Sweden (N=2) were analysed using enzyme-linked immunosorbent assay (at the time of the kidney biopsy and prior to immunosuppressant therapy), and twelve months after treatment initiation, at the time of a per-protocol repeat kidney biopsy. The Spearman’s rank correlation coefficient was used to compare levels of suPAR at baseline (BL) and month 12 (M12) with serum levels of creatinine, eGFR, urine protein-creatinine ratio (UPCR), SLEDAI-2K scores, extra-renal SLEDAI-2K scores, and renal histopathological features of activity or chronicity based on the NIH activity and chronicity index scores.Results At the time of active LN, patients had significantly higher suPAR levels compared to one year after treatment initiation (mean +/- standard error: 5.37 +/- 0.40 at BL versus 3.77 +/- 0.20 at M12; 95% CI: 0.62–2.56; p=0.002), and compared with healthy controls (2.64 +/- 0.25; BL vs HC: p<0.001; M12 vs HC: p<0.001; figure 1). Furthermore, suPAR levels at BL were not correlated with NIH activity index (AI) scores (rho=0.202; p=0.368), but a significant correlation could be seen at M12 (rho=0.595; p=0.007). In addition, suPAR levels were positively correlated with NIH chronicity index (CI) scores at BL (rho=0.541; p=0.008) and the same trend, although not significant, could be seen at M12 (rho=0.440; p=0.066; figure 2). However, a moderate and statistically significant correlation was seen between baseline suPAR levels and NIH CI scores at M12 (rho=0.554; p=0.017).Conclusions In this cohort of LN with repeat kidney biopsies, serum suPAR levels were prominently elevated in patients with active LN compared with healthy individuals and compared to 12 months after initiation of treatment. Levels of suPAR were positively correlated with histopathological activity at month 12 from treatment initiation. These findings suggest that suPAR levels may prove useful as a biomarker for monitoring LN activity and an indicator of poor prognosis, warranting further investigation.