Clinical Predictors of Underlying Histologic Activity in Patients with Lupus Nephritis: A Focus on Urinary Soluble CD163

<b>Background/Objectives</b>: We sought to evaluate the clinical predictors of underlying histologic activity in patients with lupus nephritis (LN), with a focus on urinary soluble protein CD163 (usCD163). <b>Methods</b>: We conducted a retrospective, cross-sectional study of forty-two consecutive LN patients with concurrent determination of usCD163 at the moment of kidney biopsy. A first morning void prior to the kidney biopsy was collected and usCD163 was measured by a commercial ELISA assay (EUROIMMUN, Lubeck, DE). <b>Results</b>: The study cohort had a median age at the moment of kidney biopsy of 33.5 (IQR: 24-42.7) years. The mean eGFR and median 24 h proteinuria were 76.6 ± 33.9 mL/min/1.73 m² and 1.98 (IQR: 0.83-4.52) g/day. The median activity (AI) and chronicity (CI) indices were 7 (IQR: 3-11) and 3 (IQR: 1-5), respectively. usCD163 significantly correlated with 24 h proteinuria (<i>r</i> = 0.7, <i>p</i> < 0.001), hematuria (<i>r</i> = 0.51, <i>p</i> < 0.001), and serum complement levels, C3 (<i>r</i> = -0.5, <i>p</i> = 0.001) and C4 (<i>r</i> = -0.32, <i>p</i> = 0.03), but not with eGFR (<i>r</i> = -0.23, <i>p</i> = 0.14). Regarding the histological parameters, usCD163 significantly correlated with the AI and the individual active lesions (except for fibrinoid necrosis), but not with CI or any chronic lesion. usCD163 had a higher AUC compared to the classical measures of renal involvement (proteinuria, hematuria, eGFR) for discriminating an elevated AI, but the differences between AUC reached statistical significance only for hematuria. Thus, the AUC of usCD163 was 0.74 (95%CI, 0.58-0.86) for an AI over 2, an AUC of 0.77 (95%CI, 0.61-0.88) for an AI over 3 and an AUC of 0.74 (95%CI, 0.57-0.86) for an AI of at least 9. The optimal cutoff value for usCD163 identified for all AI thresholds evaluated was 296.2 ng/mmol. <b>Conclusions:</b> usCD163 correlates with glomerular inflammation, being able to discriminate histologic activity from chronicity in patients with LN and identify minimal histologic activity, although it did not significantly outperform proteinuria.