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Objectives Systemic Lupus Erythematosus (SLE) is characterised by pronounced clinical and immunological heterogeneity. We previously identified four autoantibody-defined clusters based on 13 serological markers routinely measured in clinical practice. Whether these immunological clusters are associated with distinct long-term renal trajectories remain unclear. We aimed to determine whether autoantibody-based SLE clusters differ in long-term renal outcomes among patients with biopsy-proven lupus nephritis (LN).Methods We conducted a cohort study including 77 adult patients fulfilling the ACR and/or SLICC classification criteria for SLE who experienced a first renal flare and underwent kidney biopsy at Karolinska University Hospital. The exposure was cluster membership, based on the predominant autoantibody profile: Cluster 1 (SSA/SSB, n=19), Cluster 2 (anti-nucleosome/Sm/RNP-dsDNA, n=37), Cluster 3 (antiphospholipid antibodies [aPL], n=17), cluster 4 (ANA ever positive, otherwise seronegative, n=4). Estimated glomerular filtration rate (eGFR) was assessed at biopsy and at years 1, 2, 5, and 10. Mean differences in eGFR and odds of chronic kidney disease (CKD) across clusters over time were estimated using generalised estimating equations, adjusting for age, sex, and baseline eGFR.Results At biopsy, 61% of patients had ISN/RPS class III/IV ± V LN; median activity index was 4.0 (IQR 2.0–6.0) and chronicity index (CI) 1.0 (IQR 0.0–2.0). ISN/RPS classes were similar between clusters 2 and 3, but cluster 3 had higher CI and more vascular changes (41.2% vs 27.0%; table 1). Compared with Cluster 2, Cluster 3 (aPL-dominant) had lower eGFR during follow-up (beta: -20; 95% CI: -33, -7.5; figure 1), but this attenuated after adjustment for age and sex and baseline eGFR (beta: -0.4; 95% CI: -9.1, 8.4). Similarly, Cluster 3 showed higher odds of CKD in unadjusted models (OR: 5.5; 95% CI: 1.5, 20), which attenuated in fully adjusted models (OR 1.7; 95% CI 0.5–5.7). No other clusters differed significantly in adjusted models.Abstract PO:09:239 Table 1Baseline characteristics of patients with biopsy-proven lupus nephritis across autoantibody-defined clustersAbstract PO:09:239 Figure 1Distribution of eGFR over time by autoantibody-defined clusters in patients with biopsy-proven incident lupus nephritisConclusions Among patients with incident LN, those in the APS-like cluster exhibited lower eGFR and higher odds of CKD during follow-up compared with the nucleosome/Sm/RNP-dsDNA cluster. However, these associations were largely explained by baseline differences in renal function and demographic factors. These findings suggest that the immunological heterogeneity of SLE may contribute to differential renal vulnerability.