To explore the correlation between dynamic changes of serum complement C3 and C4 and renal function progression as well as prognosis in patients with lupus nephritis.

Patients with lupus nephritis diagnosed by renal biopsy between January 2022 and January 2025 were retrospectively enrolled. Clinical, pathological, and serum complement C3 and C4 data at baseline (Day 0) and all time points within the 0-180-day follow-up period were collected. The relative change amplitude and time-weighted mean of complement levels from Day 0 to Day 180 were calculated. Patients were classified into the persistently normal group, the recovered group, the persistently reduced group, and the newly reduced group according to complement levels at baseline and Day 180. Landmark analysis was performed with Day 180 as the landmark time point. The Kaplan-Meier method and multivariate Cox regression model were used, and LASSO-Cox regression was adopted for sensitivity analysis to assess the association between longitudinal changes in complement levels and the composite endpoint of renal function progression.

A total of 148 patients with lupus nephritis were enrolled in this study, with a median follow-up of 19.80 months. Among them, 32 patients (21.62%) developed renal function progression and were assigned to the progression group, and the remaining 116 patients were included in the non-progression group. Compared with the non-progression group, the progression group had lower baseline levels of complement C3 and C4 (all P<0.05). The proportion of patients with persistently reduced C3 and C4 in the progression group was higher than that in the non-progression group (all P<0.05). Patients with persistently reduced C3 and C4 exhibited the lowest renal progression-free rate (P<0.05). After adjustment for confounding factors, the persistently reduced C3 phenotype was independently associated with renal function progression (HR=3.120, 95%CI: 1.051-9.270, P=0.040). Indicators related to C4 showed no significant association with renal function progression (all P>0.05). LASSO-Cox sensitivity analysis verified the robustness of the findings in this study.

Dynamic change in serum complement C3, especially the persistently reduced phenotype, is independently associated with the long-term risk of renal function progression in patients with lupus nephritis. Dynamic monitoring of complement C3 level contributes to risk stratification and prognostic evaluation of lupus nephritis.