Predictors and long-term impact of sustained complete renal response in lupus nephritis patients over a median 10-year follow-up

Abstract

Objectives: Complete renal response (CRR) is a primary goal in lupus nephritis (LN) management. We examined the prevalence and predictors of sustained CRR (sCRR) and long-term outcomes. Methods: We included 142 inception cohort patients with biopsy-proven LN from two academic centres. We assessed the prevalence of sCRR achievement for ≥12 months and the impact of sCRR duration on renal flares, severe kidney function decline (≥30% eGFR decline compared with baseline), a composite end-stage kidney disease (ESKD) or death outcome, and disease damage. We analysed data over a median 121-month follow-up, using linear, logistic and Cox regression models. Results: A total of 83% of patients achieved sCRR for ≥12 months, 56.3% for ≥5 years and 20.4% for ≥10 years. Persistent hydroxychloroquine use (adjusted HR: 1.86, P = 0.004), non-nephrotic baseline proteinuria (adjusted HR: 1.71, P = 0.016) and class III vs class IV LN (HR: 1.89, P = 0.018) were associated with earlier sCRR achievement. The 5- and 10-year post-sCRR risks for renal flares decreased for every additional year on CRR. sCRR duration rather than its mere achievement reduced the risk of ≥30% eGFR decline (adjusted OR: 0.81/year, P = 0.015) and composite ESKD/death (adjusted HR: 0.75/year, P = 0.001). sCRR ≥ 12 months protected against damage accrual (adjusted β-coef=−1.17, P < 0.001). Among those with ≥100-month follow-up, sCRR ≥ 4 years protected against severe kidney function decline (adjusted OR: 0.10, P = 0.005), ESKD/death (adjusted HR: 0.11, P = 0.043) and damage accrual (adjusted β-coef=–0.81, P = 0.012). Conclusion: Persistent hydroxychloroquine, non-nephrotic baseline proteinuria and class III vs IV are associated with earlier sCRR. sCRR ≥4 years protects against ≥30% eGFR decline, composite ESKD/death and damage.