The spectrum and prognosis of Sjögren's syndrome with membranous nephropathy.

Abstract

Background: This study aims to investigate the spectrum and prognosis of membranous nephropathy (MN) in patients with Sjögren's syndrome (SS).

Methods: SS patients with biopsy-proven kidney involvement who were diagnosed at our center between April 2007 and February 2024 were retrospectively reviewed and analyzed.

Results: A total of 290 SS patients with kidney involvement were enrolled. The frequency of MN increased from 16.28% during the 2007-2010 period to 44.05% during the 2021-2024 period. After 2016, MN became the most common renal pathologic type, surpassing tubulointerstitial nephritis. PLA2R antibody or antigen was detected in 74 SS-MN patients, in whom 37 (50%) showed a negative result. Within the PLA2R-negative group, five out of 15 showed positivity for EXT1/EXT2 antigen and one out of eight for THSD7A antigen. Sixty-one SS patients with MN were followed up for >6 months, and 44 (72.13%) of them achieved renal complete remission (CR). Compared with PLA2R-negative patients, PLA2R-positive patients spent a longer time to achieve CR (1.46 ± 1.16 vs. 0.74 ± 0.47 years, P = .015) and had a higher rate of progression to the renal endpoint (8/32 vs. 1/29, P = .028). After adjusting for age, proteinuria, and eGFR, Cox regression analysis showed that PLA2R positivity remained a risk factor for CR [HR = 0.511, 95% CI (0.262 to 0.998), P = .049].

Conclusions: MN has become the predominant renal pathologic type in SS. PLA2R-positivity testing followed by EXT1/EXT2 and THSD7A testing is recommended for SS-MN patients. Although most patients can achieve renal CR, the prognosis is usually poor in PLA2R-positive SS-MN patients.