Protocadherin 7 Positive Membranous Nephropathy in China

BACKGROUND AND HYPOTHESIS: Protocadherin-7 (PCDH7) is a newly discovered rare autoantigen in membranous nephropathy (MN). Data about PCDH7-positive MN are limited. We investigate the clinicopathological characteristics and outcomes of PCDH7-positive MN. METHODS: Biopsy-confirmed PCDH7-positive MN cases identified between January 2023 and October 2024 were retrospectively analysed. Data on demographic characteristics and clinicopathological variables were collected. Subgroup analysis was performed between isolated PCDH7-positive MN and PLA2R/PCDH7 dual-positive MN cases. Serum anti-PCDH7 antibody levels were measured. RESULTS: Among 690 PCDH7-tested patients, 19 (2.75%) showed PCDH7 positivity: 7 with isolated PCDH7-positive MN and 12 with PLA2R/PCDH7 dual-positive MN. The cohort (median age 52 years; 63% male) exhibited a median serum albumin level 34.3 g/L, creatinine 0.78 mg/dL, and proteinuria 2.25 g/24h, with 1 patient having eGFR < 60 mL/min/1.73m² and 4 presenting nephrotic syndrome. Potential secondary factors were identified in 6 patients (3 with autoimmune disease, 1 with malignancy, 2 with infections); dominant IgG deposition was IgG1 in isolated PCDH7-positive MN versus IgG4 in PLA2R/PCDH7 dual-positive cases. Anti-PCDH7 antibodies were seropositive in 7 patients (5 in isolated PCDH7-positive MN and 2 in PLA2R/PCDH7 dual-positive MN). During a median 13-month follow-up period, 84% (16/19) achieved partial or complete remission. CONCLUSIONS: PCDH7-positive MN shows clinicopathological heterogeneity. PCDH7 can be detected in both PLA2R-positive and PLA2R-negative MN patients, with similar positive rates between the two groups. No consistent clinical presentation was observed in PCDH7-positive patients; instead, this group included a variety of potential secondary conditions. Additionally, anti-PCDH7 antibody levels did not correlate with clinical manifestations and outcomes in our preliminary observation.