Treating lupus nephritis patients to lupus low disease activity reduces renal relapse and preserves long-term kidney function

Abstract

<p>Objective: Lupus low disease activity state (LLDAS) is a validated treatment target in systemic lupus erythematosus (SLE) but limited studies have explored the role of LLDAS in lupus nephritis (LN). This study aims to investigate the frequency and predictors of LLDAS attainment, and its benefit on LN relapse and renal function preservation in patients with LN. Methods: Patients with LN during 2010-2020 in Queen Mary Hospital and Pamela Youde Nethersole Eastern Hospital were included in the discovery cohort and validation cohort, respectively. Complete renal response (CRR), partial renal response (PRR), LLDAS, and DORIS remission were assessed at 12 months. Regression analysis was performed to identify risk factors of LN relapse. Receiver operating characteristic (ROC) curves were used to evaluate target attainment and long-term kidney function. Results: A total of 245 LN patients (discovery cohort N=143, validation cohort N=102) were included. At 12 months, 57/143 (40%), 14/143 (10%), 70/143 (49%), 15/143 (10%) patients achieved CRR, PRR, LLDAS, and DORIS remission respectively. Attainment of both CRR/ PRR and LLDAS at 12 months was associated with best relapse-free survival (p<0.001). Multivariate analysis showed independent association of CRR/PRR and LLDAS with LN relapse risk reduction (CRR/PRR: HR=0.31, p = 0.007; LLDAS: HR=0.38, p = 0.029). LLDAS attainment predicts renal function preservation with satisfactory performance in both discovery and validation cohorts (AUC-ROC=0.71). Conclusion: LLDAS is an attainable target in LN comparable to CRR/PRR. Attainment of both targets is associated with additional benefit on relapse risk reduction. Early LLDAS attainment is associated with renal function preservation.</p>