Soluble urokinase plasminogen activator receptor (suPAR) is associated with intrarenal chronicity features on diagnostic and repeat kidney biopsies in lupus nephritis

Background Soluble urokinase plasminogen activator receptor (suPAR) is linked to organ damage in systemic lupus erythematosus (SLE). We investigated whether serum suPAR associates with histological activity and chronicity in diagnostic and 12-month repeat kidney biopsies in lupus nephritis (LN). Methods suPAR levels were determined using ELISA in serum samples from 23 LN patients (19 incident) before and 12 months after initiation of immunosuppressive therapy, and from 15 age- and sex-matched healthy controls. Correlations with NIH activity index (AI) and chronicity index (CI) scores were assessed using Spearman’s rank correlation coefficient. Results suPAR levels were higher at active LN than in controls (5.37±0.93 ng/mL versus 2.64±0.97 ng/mL; p <0.001), decreased by month 12 (3.77±0.94 ng/mL; p =0.005), but remained elevated compared with controls ( p <0.001). Baseline suPAR did not correlate with AI at baseline (rho=0.202; p= 0.368) or month 12 (rho=0.332; p =0.165), whereas month-12 suPAR correlated with month-12 AI (rho=0.595; p =0.007). Baseline suPAR correlated with CI at baseline (rho=0.541; p =0.008) and month 12 (rho=0.554; p =0.017). Month-12 suPAR showed a trend towards a correlation with month-12 CI (rho=0.440; p =0.066). Baseline suPAR correlated with baseline interstitial fibrosis (rho=0.422; p =0.044) and predicted month-12 glomerular sclerosis (rho=0.580; p =0.011) and tubular atrophy (rho=0.477; p =0.045). Month-12 suPAR correlated with month-12 glomerular sclerosis (rho=0.572; p =0.013). Conclusions Serum suPAR levels were elevated in active LN and, despite a decline, after 12 months of treatment compared with healthy individuals. suPAR levels correlated with intrarenal chronicity and predicted post-treatment glomerular sclerosis and tubular atrophy, suggesting suPAR as a potential biomarker of kidney damage in LN.