Urinary ALCAM signatures define renal activity and therapeutic response in juvenile lupus nephritis

Lupus nephritis (LN) remains a major cause of morbidity in childhood-onset systemic lupus erythematosus (SLE). Reliable non-invasive biomarkers for early diagnosis and disease monitoring are still limited. Activated leukocyte cell adhesion molecule (ALCAM) has emerged as a potential urinary biomarker reflecting renal immune injury. This study evaluated the diagnostic and monitoring performance of urinary ALCAM in juvenile LN and its correlation with disease activity scores, renal parameters, histopathological classes and indices. A controlled cross-sectional and prospective cohort study was conducted on 90 participants. Urinary ALCAM was measured in 60 pediatric patients with SLE, classified into 30 active LN and 30 active SLE non-LN patients, along with 30 age- and sex-matched healthy controls. Follow-up samples were obtained after 3 months of treatment in the active LN group. Associations with disease activity scores (SLEDAI and renal SLEDAI), renal function tests, histopathological classes, and renal pathology activity and chronicity indices were assessed. Diagnostic and monitoring performances of urinary ALCAM were analyzed using ROC curves. Baseline urinary ALCAM levels were markedly higher in active LN (1001.6 [766.4–1186] ng/mg) compared with active SLE non-LN (229.7 [182–270.5] ng/mg) and controls (38.75 [25–54.5] ng/mg), with a p < 0.001. Levels declined significantly after treatment to 163.65 [85.6–238.2] ng/mg, with a p < 0.001. Urinary ALCAM correlated positively with serum creatinine, blood urea, proteinuria, SLEDAI, and renal SLEDAI scores, while negatively with estimated glomerular filtration rate. ROC analysis showed excellent diagnostic performance of urinary ALCAM. A cut-off of > 114.6 ng/mg (AUC = 0.994, sensitivity of 93.33% and specificity of 100%) differentiated juvenile SLE patients from healthy controls. A cut-off of > 538.7 ng/mg (AUC = 0.993, sensitivity and specificity of 96.67%) distinguished patients with LN from SLE non-LN. The optimal cut-off for differentiating active LN from remission was ≤ 407 ng/mg (AUC = 0.989, sensitivity of 86.67%, and specificity of 100%). Urinary ALCAM is a reliable, sensitive and non-invasive biomarker that accurately reflects renal activity and treatment response in juvenile LN. Its strong correlations with disease activity scores and renal functions, along with high diagnostic precision across clinically relevant cut-offs, underscore its potential as a practical tool for early detection, longitudinal monitoring of renal involvement, and guiding treatment decisions particularly when renal biopsy is not feasible and also, reducing reliance on serial biopsies.