A multicenter retrospective cohort study on the efficacy and safety of mycophenolate mofetil plus hydroxychloroquine...

The mechanisms of action of mycophenolate mofetil (MMF) and hydroxychloroquine (HCQ) differ in the treatment of IgA nephropathy (IgAN), and the two may have a synergistic effect in delaying disease progression.

This multicenter retrospective cohort study included patients aged 18-60 years with biopsy-confirmed primary IgAN, with 83 patients receiving MMF plus HCQ (combined group) and 94 receiving MMF alone (MMF group). All patients had an estimated glomerular filtration rate > 45 ml/min/1.73 m² and urine protein (UP) >0.75 g/d after receiving renin-angiotensin-aldosterone system inhibitors for more than 4 weeks. Propensity score matching was performed with a matching ratio of 1:1. The primary outcomes were complete response (CR) and overall remission (OR) rates at 12 months, which were analyzed using the chi-square test. CR was defined as a 24-hour UP ≤0.3 g/d and stable renal function. The OR comprised CR and partial remission. Partial remission was defined as a >50.0% reduction from baseline in UP, with a final level of <1 g/d.

After matching, the CR rates at 12 months were 63.8% (37/58) and 37.9% (22/58) in the combination and MMF groups, respectively (odds ratio: 0.59, 95% CI 0.40-0.87, P = 0.005). OR was achieved by 53 (91.4%) and 43 (74.1%) participants in the combined and MMF groups, respectively (odds ratio: 0.45, 95% CI 0.21-0.99, P = 0.014). Kaplan-Meier analysis also showed that the probability of achieving CR and OR was significantly higher in the combination group (log-rank P = 0.008 and 0.001, respectively). Subgroup analyses showed that patients with UP >2 g/d and eGFR <60 mL/min/1.73 m² were more likely to achieve OR. The incidence of adverse events was comparable between the two groups.

Combination therapy with MMF and HCQ was associated with higher remission rates and greater reduction in UP at 12 months, particularly among those with baseline UP >2 g/d or eGFR between 45 and 60 mL/min/1.73 m², supporting its potential short-term renal benefit.