Abstract

Class IV-S lupus nephritis is often associated with more necrosis and fewer subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive of necrotising glomerular inflammation found in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. ANCAs are present in a significant proportion of patients with lupus nephritis. Here we determine whether ANCAs are associated with distinct clinical and histopathologic features of lupus nephritis. Thirty-two ANCA-positive biopsies were compared to 222 ANCA-negative biopsies from patients with lupus nephritis. The majority (82%) of ANCA-positive patients had antimyeloperoxidase antibodies. Class IV-S lupus nephritis and glomerular necrosis were significantly more common (36% vs. 16% and 35% vs. 15%, respectively) and isolated Class V lupus nephritis significantly less common (10% vs. 29%) in the ANCA-positive group. ANCA-positive patients had significantly higher dsDNA titers (335u/ml vs. 52u/ml), significantly lower serum C4 concentrations (0.125g/L vs. 0.15g/L) and significantly higher serum creatinine (130μmol/L vs. 84μmol/L) at the time of biopsy. Hence ANCAs appear to influence the histological pattern of lupus nephritis and are associated with worse baseline renal function and more active lupus serology. There was no significant difference in outcome between groups when matched for severity of disease and treatment using propensity scoring. Thus, further studies are needed to examine whether ANCAs in patients with lupus nephritis have a pathogenic role and whether they are associated with worse renal outcomes or are simply a marker of more severe disease.

Highlights

  • antineutrophil cytoplasmic antibody (ANCA) appear to influence the histological pattern of lupus nephritis and are associated with worse baseline renal function and more active lupus serology

  • A total of 254 biopsy specimens from 203 patients with a histologic diagnosis of lupus nephritis (LN) identified in our hospital renal biopsy database had ANCA serology assessed within 6 months of biopsy

  • A KaplanMeier survival analysis of these matched groups confirmed no significant difference in time to RRT or death between the 2 groups. This was a retrospective analysis of a large cohort of patients with LN over a long follow-up period (1997–2015) performed to determine whether ANCAþve serology in patients with LN is associated with different histopathologic features on renal biopsy specimens and different clinical outcomes

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Summary

Introduction

ANCAs appear to influence the histological pattern of lupus nephritis and are associated with worse baseline renal function and more active lupus serology. The classification of lupus nephritis (LN) was revised with the International Society of Nephrology (ISN)/ Renal Pathology Society (RPS) Classification in 2003,1 which subdivides Class IV LN into segmental (IV-S) and global (IV-G) subclasses based on whether endocapillary involvement in diffuse proliferative LN is predominantly segmental (involving 50% of the glomerular tuft). Part of the rationale for this subdivision of Class IV LN was based on a study by the Lupus Nephritis Collaborative Study Group, which found that patients with “severe” focal segmental glomerular inflammation (involving >50% of glomeruli in the biopsy specimen) tended to have different histopathologic features on biopsy and worse clinical outcomes, with lower 5-year remission rates and poorer renal survival at 10 years (despite similar baseline clinical parameters and similar treatment).[2] In that study, diffuse segmental glomerular inflammation was associated with more necrosis and fewer subendothelial immune deposits compared with diffuse global glomerular inflammation. As yet, there is no convincing evidence in the literature that ANCA positivity in patients with LN is associated with different histopathologic features of glomerular inflammation

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