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Repeat biopsies in membranous lupus nephritis in the era of target antigen identification
Elodie Bernhard1, Hamza Sakhi1,2,3, Julie Oniszczuk2,3
1Univ Paris Est Créteil, 94010, Créteil, France.
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.
Insights
In membranous lupus nephritis (LN), exostosin (EXT) and neural cell adhesion molecule 1 (NCAM1) expression can change over time. Thrombotic microangiopathy (TMA) and chronicity index (CI) significantly impact kidney disease progression.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Membranous lupus nephritis (LN) is characterized by immune complex deposition in glomeruli.
- Positivity for exostosin 1/2 (EXT) in initial biopsies is linked to a lower chronicity index (CI) and reduced risk of end-stage kidney disease (ESKD).
- Repeat kidney biopsies (RKB) can reveal changes in CI and histological class, carrying prognostic significance.
Purpose of the Study:
- To investigate the variability of exostosin (EXT) and neural cell adhesion molecule 1 (NCAM1) expression in repeat kidney biopsies (RKB) of patients with membranous lupus nephritis (LN).
- To assess the association of these antigen expression changes with histological class transition (III/IV+V) and renal outcomes.
- To identify predictors of kidney disease progression in membranous LN.
Main Methods:
- Retrospective analysis of 78 kidney biopsies from 30 patients with membranous lupus nephritis (LN).
- Evaluation of exostosin (EXT) and neural cell adhesion molecule 1 (NCAM1) expression at initial and repeat kidney biopsies (RKB).
- Correlation of antigen expression changes with clinico-pathological data, class transition, thrombotic microangiopathy (TMA), and renal outcomes including ESKD.
Main Results:
- Target antigen expression switch (EXT or NCAM1) occurred in 10% of cases and was associated with favorable renal outcomes.
- No significant differences in baseline characteristics, CI increase, class transition rates, or renal outcomes were observed between EXT-positive and EXT-negative groups.
- Higher CI and serum creatinine at first biopsy, and higher CI and TMA rate at second biopsy were associated with adverse renal outcomes (ESKD or >40% GFR decrease).
- Thrombotic microangiopathy (TMA) on any follow-up biopsy was more frequent in patients with adverse outcomes.
Conclusions:
- Exostosin (EXT) and neural cell adhesion molecule 1 (NCAM1) expression can vary in repeat kidney biopsies (RKB) during membranous lupus nephritis (LN).
- EXT positivity does not appear to confer long-term protection against disease progression in this cohort.
- Increased chronicity index (CI) and the presence of thrombotic microangiopathy (TMA) are significant predictors of poor renal outcomes in membranous LN.
