Repeat biopsies in membranous lupus nephritis in the era of target antigen identification

Abstract

In membranous lupus nephritis (LN), positivity for the target antigen exostosin 1/2 (EXT) is associated with a lower chronicity index (CI) at first biopsy and a lower risk of progression to end-stage kidney disease (ESKD) compared to EXT-negative patients. Repeat kidney biopsies (RKB) in LN may reveal increasing CI and class transition with prognostic significance. In a cohort of membranous LN with RKB, we assessed the variation in EXT and neural cell adhesion molecule 1 (NCAM1) expression and their association with class III/IV + V transition and renal outcomes. Thirty patients with 78 biopsies were enrolled. Index biopsies included 60% EXT-NCAM1-, 34% EXT + NCAM1-, 3% EXT-NCAM1 + and 3% EXT + NCAM1 + cases. Target antigen switch occurred in 3 (10%) cases (2 EXT + to EXT-; 1 NCAM1- to NCAM1 +) with favorable renal outcomes. EXT-positive and EXT-negative groups had similar clinico-pathological characteristics at baseline and at the end of follow-up, with comparable numbers of RKB, median CI increase, class transition rates, and renal outcomes. After a median follow-up of 8.8 years, 9 (32%) patients developed ESKD or glomerular filtration rate decrease > 40%. These patients exhibited higher median first biopsy CI (p = 0.04) and higher median serum creatinine level (p = 0.01), higher median CI (p = 0.02), and higher thrombotic microangiopathy (TMA) rate (p = 0.03) at second biopsy. TMA on any follow-up biopsy was more frequent in the adverse outcome group (p = 0.001). Not only EXT but also NCAM1 expression may vary in RKB during membranous LN. EXT-positive and EXT-negative patients had similar presentation and course, while TMA and CI compromised renal outcomes.

Keywords: Exostosin; Lupus nephritis; Membranous nephropathy; NCAM1; Repeat kidney biopsies; Target antigen.