Serologic Discrimination of Histologic Classes in Lupus Nephritis: A Cross-Sectional Analysis with Exploratory 12-Month Outcomes

BACKGROUND: Anti-dsDNA positivity and hypocomplementemia are markers of active lupus nephritis (LN), but their ability to discriminate between histologic phenotypes remains underexplored, particularly for mixed proliferative/membranous LN (mixed LN). We compared baseline serologic markers across proliferative LN, membranous LN, and mixed LN, and evaluated their discriminative performance for histologic class. METHODS: We conducted a retrospective cross-sectional study of 132 patients with biopsy-proven LN, categorized according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification into proliferative LN (class III/IV), membranous LN (class V), and mixed LN (class III/IV+V). Baseline anti-dsDNA and complements C3 and C4 were compared across groups. Receiver operating characteristic (ROC) analysis assessed the ability of individual and combined markers to discriminate between histologic classes. Kidney outcomes at 12 months were explored in a secondary cohort (n=88). RESULTS: Of 132 patients, 57 had proliferative LN, 32 had membranous LN, and 43 had mixed LN. Anti-dsDNA was significantly higher, and C3 and C4 significantly lower, in proliferative and mixed LN compared to membranous LN (P<0.05 for all), while proliferative and mixed LN did not differ significantly. On ROC analysis, individual markers achieved AUCs of 0.68-0.71 for distinguishing proliferative or mixed LN from membranous LN, with combined models yielding AUCs of 0.73. However, discrimination between proliferative and mixed LN was poor (combined AUC 0.62). At 12 months, kidney outcomes were comparable across groups. CONCLUSIONS: Mixed LN exhibits a serologic profile resembling proliferative LN, both sharing elevated anti-dsDNA and low complement levels, but distinct from membranous LN. Serology could inform suspicion for LN class but cannot replace kidney biopsy.