Efficacy and Safety of Hydroxychloroquine in IgA Nephropathy Associated with Nasopharyngeal or Intestinal Mucosa Infection

Background: Hydroxychloroquine (HCQ) has shown efficacy in treating Immunoglobulin A nephropathy (IgAN). However, no cohort study has evaluated its effectiveness and safety specifically in IgAN patients with nasopharyngeal or intestinal mucosal infection (MI). Methods: This prospective multicenter cohort study enrolled patients aged >18 years with IgAN, who had received optimized renin-angiotensin-aldosterone system inhibitor (RAASi) therapy for at least 1 month. Eligible participants had a 24-hour urinary protein-to-creatinine ratio (UPCR) of 0.75-3.5 g/g and an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m². Patients were stratified into two groups based on the presence (MI group) or absence (non-mucosal infection [NMI] group) of nasopharyngeal or intestinal MI symptoms at IgAN diagnosis. Both groups received HCQ treatment, and efficacy and safety were assessed. Results: The study included 192 patients in the MI group and 177 in the NMI group. The mean age was 37.58 years, mean eGFR was 85.27 mL/min/1.73m², and mean baseline 24-hour UPCR was 1.92 g/g. At 12 months, the MI group exhibited a reduction in 24-hour UPCR from 1.90 ± 0.76 g/g to 0.77 ± 0.31 g/g (mean reduction 59.4%), while the NMI group showed a decline from 1.94 ± 0.67 g/g to 1.08 ± 0.44 g/g (mean reduction 44.5%). Complete remission was achieved in 58.3% (n = 112) of the MI group and 47.5% (n = 84) of the NMI group (HR: 0.57, 95% CI: 0.19-2.10, P < 0.001). The overall response rate was 66.3% (n = 127) in the MI group and 57.9% (n = 102) in the NMI group (HR: 0.53, 95% CI: 0.16-1.96, P < 0.001). Renal function remained stable, no severe adverse events were reported. Conclusion: HCQ combined with optimized RAASi effectively and safely reduced proteinuria in IgAN patients with MI.