Predictive value of CD44 in membranous nephropathy with focal segmental glomerular sclerosis lesions treated with calcineurin inhibitors

Calcineurin inhibitors (CNIs) are effective immunosuppressive agents for idiopathic membranous nephropathy (iMN). Focal segmental glomerular sclerosis (FSGS) lesions, frequently observed in MN, have been identified as indicators of poor prognosis. This retrospective study enrolled 71 patients with biopsy-proven iMN accompanied by FSGS lesions, all of whom were initially treated with CNIs. This study identified independent risk factors for renal function progression and assessed the predictive significance of CD44. The primary outcome was defined as a 50% decline in the eGFR. Fifty-eight patients (81.7%) had CD44+ visceral epithelial cells (VECs), with 36 (36/71, 50.7%) demonstrating a linear positive pattern, of whom 19 patients showed a strong positive (3+) linear distribution in VECs. The patients with a strong linear distribution of CD44+ VECs had a higher rate of progression to the primary outcome (13/19 vs. 6/52, p 0.001). The model based on age (OR, 1.134; p = 0.004), failure to achieve CR with CNIs treatment (non-CR) (OR, 6.924; p = 0.042), and strong linear CD44+ VECs (OR, 37.139; p 0.001) showed good discrimination in predicting renal function decline, with a receiver operating characteristic AUC of 0.929 (0.871-0.986) (p 0.001). Therefore, patients with strong linear CD44+ VECs showed a lower remission rate and a higher rate of progression to the primary outcome. The model, which incorporated age, non-CR status, and strongly linear CD44+ VECs, demonstrated effective discrimination in predicting renal function deterioration.