POS0554 INFLAMMATORY FIBROSIS PRECEDES LOSS OF KIDNEY FUNCTION IN LUPUS NEPHRITIS
Authors: A. Fava, S. Malvica, P. Fenaroli, S. Bagnasco, J. Hodgin, P. Izmirly, H. M. Belmont, K. Preisinger, J. P. Buyon, L. Magder, M. Petri, A. Rosenberg
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Interstitial fibrosis in lupus nephritis (LN) is often infiltrated by immune cells. However, this is typically regarded as nonspecific "scar reaction" rather than active disease requiring treatment. In contrast, scar inflammation in kidney allografts is associated with chronic rejection and treated with immunosuppression. <h3>Objectives:</h3> To investigate the relationship between inflammatory fibrosis and kidney disease progression in LN. <h3>Methods:</h3> Interstitial fibrosis and tubular atrophy (IFTA) were scored in 124 kidney biopsies from patients classified as LN according to the 2018 International Society of Nephrology/Renal Pathology Society criteria. Inflammation in areas of IFTA (i-IFTA) was graded 0-3 by 2 operators and reviewed by a senior renal pathologist based on extent according to the Banff Classification of Allograft Pathology (&lt;10%, 10-25%, 26-50%, &gt;50%, respectively). Glomerular filtration rate (GFR) was estimated using the CKD-EPI equation. Significant GFR loss was defined as a decline of &gt;15 ml/min at 3 years from biopsy or end-stage kidney disease (ESKD) by year 3 requiring dialysis or transplant. <h3>Results:</h3> The clinical and demographic characteristics of the cohort are summarized in Table 1. IFTA was observed in 88/124 (71%) biopsies, and i-IFTA was identified in 76/88 (86%) cases. The distribution of i-IFTA grades according to the degree of IFTA is illustrated in Figure 1A. Of the 53 IFTA cases with 3-year follow-up data available, significant GFR loss was observed in 22/53 (42%) cases. As expected, IFTA was associated with GFR loss (p for trend = 0.03). In patients with moderate-to-severe IFTA (grade 2 or 3), the degree of i-IFTA was associated with higher risk of significant GFR loss (Figure 1B). The risk of significant GFR loss in this subgroup was 0/2 (0%), 1/2 (50%), 3/4 (75%), and 7/8 (87.5%) for i-IFTA grades 0, 1, 2, and 3, respectively (p for trend = 0.018). <h3>Conclusion:</h3> Inflammation in areas of IFTA is frequently observed in LN and exhibits substantial heterogeneity in its severity. For patients with baseline IFTA grades &gt;1, the degree of i-IFTA emerged as a strong predictor of poor renal outcomes. These data support the routine scoring of i-IFTA in LN due to its prognostic implications and nominate i-IFTA as a potential therapeutic target. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Andrea Fava Sanofi, AnnexonBio, AstraZeneca, UCB., Silvia Malvica: None declared, Paride Fenaroli: None declared, Serena Bagnasco: None declared, Jeffrey Hodgin AstraZeneca, Eli Lilly, Gilead, Janssen, Moderna, Novo Nordisk, Regeneron, Peter Izmirly: None declared, H. Michael Belmont Aurinia, Alexion, KAtherine Preisinger: None declared, Jill P Buyon Bristol-Myers Squibb(BMS), GlaxoSmithKlein(GSK), Related Sciences, Laurence Magder: None declared, Michelle Petri Arthros-FocusMedEd, Aurinia, Amgen, AnaptysBio, Annexon Bio, Argenx, AstraZeneca, Axdev, Boxer Capital, Cabaletto Bio, Caribou Biosciences Inc, CVS Health, Escient Pharmaceuticals, Exo Therapeutics, Gentibio, GSK, Horizon Therapeutics, iCell Gene Therapeutics, Idorsia Pharmaceuticals, Kira Pharmaceuticals, Eli Lilly, MedShr, Momenta Pharmaceuticals, Nexstone Immunology, Nimbus Lakshmi, Proviant, Regeneron Pharmaceuticals, Sanofi, Seismic Therapeutic, Sinomab Biosciences, Takeda, Tenet Medicines Inc, TG Therapeutics, UCB, Zydus. DSBM: CTI Clinical Trial and Consulting Services, Emergent Biosolutions, IQVIA, Merck EMD Serono., AstraZeneca, Aurinia, Eli Lilly, Exagen, GSK, Janssen., Avi Rosenberg: None declared.