Does the Time to the Onset of Lupus Nephritis Impact Renal Disease Presentation and Outcomes?

Objectives Lupus nephritis (LN) most commonly develops in the initial years after the onset of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the impact of the time to LN onset on the clinical presentation and outcomes of LN. Methods We included 246 inception cohort patients who developed LN at the time of clinic entry or during follow-up. We categorized patients into 3 groups based on the time to LN onset: group 1 (early, ≤1 year, 160 patients), group 2 (intermediate, >1 to ≤5 years, 42 patients), and group 3 (delayed, >5 years, 44 patients). The outcomes assessed were complete proteinuria recovery (CPR) at 1 year, the occurrence of an adverse composite outcome (end-stage kidney disease [ESKD], a sustained ≥40% decline in estimated glomerular filtration rate [GFR], or death), and the development of subsequent LN flares. Kaplan-Meier (KM) curves with log-rank tests, as well as univariable and multivariable Cox proportional hazard models, were conducted to assess the associations between the outcomes and the study groups. Results At baseline, the median [IQR] age of our cohort was 34.3 [26.2, 44.7] years, with a median disease duration of 0.6 [0.2, 2.6] years. Delayed LN patients were older at baseline (LN onset), had higher (SLICC)/ACR Damage Index (SDI), and used immunosuppressives less frequently. They were the least likely to achieve CPR at 1 year (53.9% for early LN vs. 47.6% for intermediate LN vs. 27.9% for delayed LN, p=0.01). Intermediate LN patients had the highest odds of experiencing an adverse composite outcome (27.5% for early LN vs. 50.0% for intermediate LN vs. 40.9% for delayed LN, p=0.01) on long-term follow-up (median of 8.5 [4.2, 15.5] years, with 2401 patient-years), with no significant difference in subsequent flares. In the KM curves, intermediate LN was associated with the shortest time to the adverse composite outcome (7.2 [2.9, 12.5] years for early LN vs. 4.4 [1.6, 14.3] years for intermediate LN vs. 7.0 [1.6, 13.9] years for delayed LN, p=0.02), with no significant differences in time to subsequent flares (Figure 1). In the Cox proportional hazard models, compared to early LN, intermediate LN was associated with a heightened risk of developing the adverse composite outcome and showed a trend toward a higher association with subsequent LN flares. Figure 1 A-B. Kaplan-Meier curves showing the differences between the early, intermediate, and delayed lupus nephritis groups in: A- Time to adverse composite outcome (end-stage kidney disease, a sustained ≥40% decline in eGFR, or death) B- Time to subsequent lupus nephritis flare Conclusion Intermediate LN, occurring 1 to 5 years after SLE onset, is associated with the worst renal outcomes.

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