Beyond renal response: sustained systemic disease control protects against adverse long-term outcomes in lupus...

Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS) are associated with improved outcomes in SLE; however, their value in lupus nephritis (LN) remains unexplored. We sought to evaluate their prognostic value on organ damage accrual, renal flares and chronic kidney disease in patients with LN.

Multicentre retrospective cohort study of patients with biopsy-proven LN who achieved renal response. Enrolment date was the time of first renal response. Longitudinal data were analysed using Cox proportional hazards models. Modified LLDAS (mLLDAS) and DORIS (mDORIS) attainment and sustained durations were evaluated.

155 patients with 1703 visits were included. During a median follow-up of 3.5 years (IQR 4.5), 127 patients (81.9%) achieved mLLDAS and 92 (59.4%) achieved mDORIS. Both states demonstrated robust protective effects across all outcomes. For organ damage, mLLDAS attainment was associated with 85% risk reduction (adjusted HR (aHR 0.15, 95% CI 0.07 to 0.32), while mDORIS conferred a 79% reduction (aHR 0.21, 95% CI 0.08 to 0.55). Periods under mLLDAS were also associated with a 73% reduction in renal flare risk (aHR 0.27, 95% CI 0.14 to 0.51), with similar effects for mDORIS. Sustained achievement resulted in progressively greater protection, with the strongest effects seen for ≥24 consecutive months. Early attainment protected against damage accrual (aHR 0.31, 95% CI 0.16 to 0.61) and renal flares (aHR 0.51, 95% CI 0.29 to 1.00).

Following renal response, achievement of mLLDAS and mDORIS is strongly associated with improved outcomes in LN patients. Earlier attainment and longer duration in these states confer progressively greater protection.