Urinary soluble CD163 is useful to predict lupus nephritis activity and to monitor standard-of-care therapy response.

Objectives: This study aims to assess urinary soluble CD163 normalized to creatinuria (usCD163/Cre) alongside conventional biomarkers as indicators of renal activity and therapeutic response in lupus nephritis (LN).

Methods: A monocentric and retrospective cohort analysis involving 214 patients with systemic lupus erythematosus (SLE) was conducted, among whom 129 were referred as LN and assessed longitudinally. Of these, 39 underwent kidney biopsy at sample collection. Data were extracted from medical records, including metrics on renal activity (SLEDAI-R), histological characteristics, and therapeutic response according to KDIGO 2024 outcome criteria. The characteristics of usCD163/Cre (ELLA-G2) were compared against routinely used biomarkers and confounding factors including renal function and concomitant medication use.

Results: The cross-sectional analysis indicated that usCD163/Cre (AUC = 0.999), spot urine protein/creatinine ratio or PCR; (AUC = 0.994), and serum albumin levels (AUC = 0.940) distinguished between active LN and inactive states, and correlated with SLEDAI-R scores. At the time of kidney biopsy, usCD163/Cre was the only reliable predictor of histological activity (AUC= 0.962; threshold 1200 ng/mmol). During follow-up assessments, usCD163/Cre outperformed PCR to discriminate disease flares (>520 ng/mmol), and categorization into low- (<520 ng/mmol), medium- (520-1200 ng/mmol), and high- (>1200 ng/mmol) usCD163/Cre levels at 3- and 6-months, following therapy introduction, allows to predict complete, partial and non-responders as an independent factor.

Conclusion: Our findings support the involvement of CD163 positive macrophages (M2c) in the pathophysiology of LN and advocate for the inclusion of usCD163/Cre measurement in the standard of LN management to assess LN flare episodes and as an early predictor of therapy response.