Early eculizumab treatment improves renal outcomes in pediatric lupus nephritis with thrombotic microangiopathy

BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Patients with lupus nephritis (LN) complicated by thrombotic microangiopathy (TMA) exhibit high mortality and poor renal outcomes. Eculizumab, a humanized monoclonal antibody inhibiting terminal complement C5 activation, has been recommended for the treatment of TMA caused by alternative complement pathway activation. This study evaluated the clinical efficacy of eculizumab in pediatric LN-associated TMA. METHODS: We retrospectively analyzed children diagnosed with LN-TMA from July 2009 to January 2025. All patients met the 2019 EULAR/ACR SLE classification criteria and were aged <18 years. TMA diagnosis required microangiopathic hemolytic anemia, thrombocytopenia, and organ involvement, excluding TTP (ADAMTS13 deficiency), Shiga toxin-associated HUS, antiphospholipid antibody syndrome, infections, hypertension, or drug-induced TMA. Overall survival, renal response, and hematologic recovery were analyzed. RESULTS: Among 22 LN children with TMA, four received ≥1 dose of eculizumab (eculizumab group), while 18 served as controls. Baseline characteristics showed no significant differences. Eculizumab treatment was initiated ∼7 days following TMA diagnosis. By week 1, the eculizumab group demonstrated significant reductions in serum creatinine and improved eGFR, sustained through 16 weeks, whereas controls showed delayed improvement by week 8. Time to partial renal response was shorter with eculizumab (1.67 vs. 3.64 months, P < .05). Complete renal remission rates trended higher with eculizumab (100% vs. 50.0%, P = .29). Kaplan-Meier analysis confirmed superior 1-year complete remission rates in the eculizumab group (P = .003). Hemoglobin recovery was faster with eculizumab. No deaths or severe infections occurred, affirming its safety. CONCLUSION: In pediatric LN with TMA, eculizumab outperforms conventional therapy by accelerating renal recovery. Early use-after excluding TTP, infections, and drug-related causes-may mitigate renal damage and improve outcomes. Given that this is a retrospective study with a small sample size, the findings require validation from larger-scale clinical studies.