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2025 KDIGO guidelines indicates that mycophenolate mofetil (MMF) and hydroxychloroquine (HCQ) demonstrate certain efficacy in Chinese patients with immunoglobulin A nephropathy (IgAN). Given the differing mechanisms of action between the two drugs, this study aims to evaluate the efficacy of MMF combined with HCQ in the treatment of IgAN.
This multicenter retrospective cohort study included patients aged 18-60 years with a renal biopsy-confirmed diagnosis of IgAN who had been treated with either MMF combined with HCQ or monotherapy with MMF for at least 12 months. Additionally, all patients had a 24-hour urine protein (UP) > 0.75 g/d after receiving standard supportive treatment for more than four weeks and estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m2. Any secondary form of IgAN, or major hepatic, cerebrovascular, or cardiovascular comorbidities, or prior kidney transplantation, or any prior immunosuppressive therapy were excluded. The primary endpoints were reduction of 24-hour UP and eGFR and secondary endpoints were complete remission (CR) and overall remission (OR).
A total of 177 IgAN patients were screened, of whom 83 received MMF plus HCQ and 94 received MMF monotherapy. To further ensure comparability between them, we conducted propensity score matching at a 1:1 ratio, focusing on matching their UP, serum albumin and eGFR levels, resulting in the establishment of 55 patients in the combined group and 55 in the MMF group (Table 1).
The combined group exhibited significantly lower UP levels than the MMF group at both 3-month [1.12 (0.99) vs. 1.43 (1.05), P = 0.034)] and 6-month [0.79 (0.67) vs. 1.00 (0.76), P = 0.049, Figure 1A]. In terms of percentage change from baseline at 3 months, UP decreased by 58.76% and 46.53% in the combined group and the MMF group, respectively (P<0.001). At the 6 and 9 months, the decrease was more pronounced in the combined group (-69.48% vs. -63.14%, P=0.008; -78.07% vs. -73.92%, P=0.037, respectively, Figure 1B). Changes in eGFR and serum albumin from baseline were shown in Figure 1C-F and were comparable between groups. In the matched cohort, the combined group also significantly greater reductions in UP percentage at both 3 and 6 months compared to the MMF group (-58.49% vs. -45.28%, P = 0.005; -67.51% vs. -61.53%, P = 0.039, respectively).
Kaplan-Meier survival curve results showed that the incidence of CR and OR were significantly greater in the combined group than in the MMF group at 12 months (P=0.011, P=0.028, respectively, Figure 2A-B). Multivariate Cox regression analysis revealed that combined group was associated with a higher likelihood of achieving 12-month CR [HR 0.55 (95% CI 0.36-0.85), P=0.008] (Table 2). After PSM, a statistically significant difference was observed between the two groups only in CR (log-rank P=0.004, Figure 2C), whereas no difference was found in OR (log-rank P=0.086, Figure 2D). Subgroup analyses showed the benefit of combined group was consistent across all subgroups (all HR <1 favor combined) in both full and matched cohort (Figure 3).
The combination of MMF and HCQ is associated with a greater reduction in proteinuria and achieved CR at an earlier stage compared with MMF in IgAN patients.
