A membranous nephropathy variant mimicking minimal change disease

This study characterizes a novel disease pattern of membranous nephropathy (MN) that exhibits overlapping clinicopathological features with minimal change disease (MCD), termed 'MCD-like MN'. Patients with histologically confirmed MN showing sparse and segmental subepithelial electron-dense deposits (EDD) but clinically resembling MCD were enrolled, alongside age- and gender-matched classic MCD and MN controls. Clinicopathological parameters were compared across groups. MN-associated antigens and MCD-related podocyte antigens were analyzed in renal tissues and serum. Among 107 archival MCD cases re-evaluated, 16 were reclassified as MCD-like MN based on EDD presence. Pathologically, these cases demonstrated IgG deposition in podocytes (62.5%), significantly higher than classic MCD (6.2%), but lacked complement activation and showed milder interstitial fibrosis compared to MN. Clinically, MCD-like MN patients presented a shorter disease duration and higher complete remission rates compared to MN (p < 0.01), resembling classical MCD. Additionally, they had lower serum creatinine levels than MCD patients (p < 0.01), which were more similar to MN levels. Furthermore, MN-associated antigens were detected in MCD-like MN cases and some of the serum antibodies' levels were increased, suggesting shared pathogenesis with MN, albeit with distinct immune features. Besides, spectrometry counts of podocyte antigens were not increased, and serum anti-podocyte antibodies were either absent or not elevated compared to MCD patients, ruling out antibody-mediated podocytopathy. Collectively, MCD-like MN represents a distinct MN subtype with atypical MCD-like clinicopathological features, likely driven by a unique immune mechanism divergent from both classic MN and MCD.