A study of calcineurin inhibitors in comparison with intravenous cyclophosphamide for initial induction treatment of lupus nephritis class Ⅲ, Ⅳ, V in Chinese children

Background Lupus nephritis (LN) is one of the most common secondary glomerulonephritis in children, and may progress to end-stage kidney disease if remission induction is not successful. Currently, the recommended induction treatment for lupus nephritis class Ⅲ/Ⅳ/V are corticosteroids combined with cyclophosphamide (CYC). Although tacrolimus has demonstrated comparable efficacy to CYC in adult patients with LN, its effectiveness and safety in the treatment of childhood lupus nephritis (cLN) have not been extensively investigated, particularly in comparison to cyclophosphamide (CYC). The objective of this study is to retrospectively assess the effect of calcineurin inhibitors (CNIs) compared to CYC as the initial induction therapy for class Ⅲ/Ⅳ/Ⅴ cLN. Methods cLN of class Ⅲ/Ⅳ/V treated initially with intravenous CYC or CNIs from January 2009 to January 2022 were included. The collected clinical, pathological, and treatment data were analyzed to assess and compare the efficacy and safety of CNIs versus CYC. Results A total of 75 LN patients were eligible. 46 patients received corticosteroids combined with intravenous CYC for induction remission, while 29 patients with oral CNIs, mainly tacrolimus. The CNI group had a significantly higher complete remission (CR) rate (55.2%) compared to the CYC group (17.4%) after 3 months of treatment, and this difference remained at 6 months (62.1% vs 26.1%). The reduction of proteinuria was also more significant in the CNI group compared to the CYC group at 3-month induction. The overall incidence of adverse effects was significantly lower in CNI than in CYC (17% vs 63%, p = 0.032). Multiple logistic regression analysis identified edema, anti-dsDNA, and CYC as risk factors for non-remission after 6-month induction therapy. Conclusions This study demonstrates that CNIs are safer and more effective than CYC for quickly reducing proteinuria and achieving higher CR rate in initial induction treatment for lupus nephritis class III/IV/V. Clinical Trial Registration ChiCTR2300075587.