Identification of two distinct clusters in membranous lupus nephritis patients: recognition of a high-risk profile based on unsupervised analysis.

Background and hypothesis: Membranous lupus nephritis (MLN) traditionally includes class V (alone) and may be associated with other classes (III or IV). The clinical, therapeutic and prognosis relevance of the classification remains controversial.

Methods: A retrospective cohort of 412 MLN patients from the First Affiliated Hospital of Sun-Yat Sen University was followed for a median of 65.68 (IQR: 23.13-131.70) months. The primary outcomes were adverse renal events including all-cause death and end-stage renal diseases (ESRD). Phenotypes were identified and validated using unsupervised clustering analysis (K-means), Principal component analysis (PCA) and decision tree analysis.

Results: Distinct clinical and pathological differences were noted for the traditional Class IV + V, the traditional Class V + III and Class V exhibited high similarities in clinical features and prognosis (P = 0.074). K-means clustering revealed high-risk (n = 180) and low-risk groups (n = 232), with significant differences in adverse renal outcomes (9.2% vs. 4.1%, P < 0.001). To recognize the high-risk profile of MLN patients, a decision tree based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Score, hemoglobin, serum creatinine, traditional classification, and activity index of renal biopsy accurately clustered patients in the development (95.8% accuracy) and validation (87.1% accuracy) cohorts.

Conclusions: Two novel phenotypic clusters, more predictive than traditional classifications, enhance high-risk profile identification and prognostic accuracy.