Abstract
BACKGROUND: Hydroxychloroquine (HCQ) had shown efficacy in treating Immunoglobulin A nephropathy (IgAN). There are currently no clinical studies evaluating whether the efficacy and safety of HCQ differ in IgAN with concurrent nasopharyngeal or intestinal mucosal and non-mucosal infections at the time of diagnosis. METHODS: This prospective multicenter cohort study enrolled patients aged > 18 years with biopsy-proven IgAN who had received optimized renin-angiotensin-aldosterone system inhibitor (RAASi) therapy for at least 1 month, 24-hour urinary protein creatinine ratio (UPCR) of 0.75–3.5 g/g and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m². At the time of IgAN diagnosis, patients were divided into the mucosal infection (MI) group and the non-mucosal infection (NMI) group based on whether they had mucosal infections, both groups of patients were treated with HCQ. RESULTS: The study enrolled a total of 369 participants, consisting of 192 MI patients and 177 NMI patients. The mean age of the study participants was 37.58 years, with an average eGFR of 85.27 mL/min/1.73 m² and a baseline 24-hour UPCR of 1.92 g/g. After 12 months, the MI group showed a significant reduction in 24-hour UPCR, decreasing from 1.90 ± 0.76 g/g to 0.77 ± 0.31 g/g, with a mean reduction of 58.6%. In contrast, the NMI group had a more modest decline, from 1.94 ± 0.67 g/g to 1.08 ± 0.44 g/g, averaging a 43.8% reduction. Complete remission rate was achieved in 58.3% (n = 112) of the MI group and 47.5% (n = 84) of the NMI group (HR: 1.56, 95% CI: 1.15–2.13, P = 0.004). The overall remission rate was 66.1% (n = 127) in the MI group and 57.6% (n = 102) in the NMI group (HR: 1.65, 95% CI: 1.23–2.21, P < 0.001). Renal function remained stable, no severe adverse events were reported. CONCLUSION: HCQ combined with optimized RAASi safely and effectively reduced proteinuria in IgAN, with particularly superior efficacy observed in patients with concurrent nasopharyngeal or intestinal MI. CLINICAL TRIAL NUMBER: Not applicable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-025-04509-1.