Hydroxychloroquine use in pediatric IgA nephropathy

Hydroxychloroquine (HCQ) has been identified as an interesting treatment option in adult IgA nephropathy. HCQ targets the active toll-like receptors in IgA nephropathy. The purpose of this study was to explore the effects and potential benefits of HCQ for childhood-onset IgA nephropathy (cIgAN).

We conducted a retrospective multicenter cohort study including 16 children with biopsy-proven cIgAN treated with HCQ in tertiary pediatric nephrology centers in Canada and France. HCQ was prescribed as an adjunctive therapy for persistent proteinuria despite standard-of-care treatment and/or with a steroid-sparing intent. Clinical and histological data were collected at baseline, and urine protein-to-creatinine ratios (UPCR) and estimated glomerular filtration rates (eGFR) were documented at HCQ initiation, 3, 6, 9, and 12 months of follow-up. Iterative biopsies before and after the introduction of HCQ (n = 8) were compared. Steroid exposure was assessed in both groups, and safety monitoring data for HCQ therapy were documented.

Median age was 12.74 [11.33-14.07] years, with 37.5% male participants. Most (15/16, 93.8%) participants received steroid therapy, and all (16/16, 100%) were treated with renin-angiotensin-aldosterone system blockers. HCQ was initiated within a median time of 519 [249-1016.5] days from initial diagnosis. UPCR at 3, 6, 9, and 12 months after HCQ initiation significantly decreased, both in absolute and relative metrics. A decrease of 50% was noted at 12 months of follow-up. eGFR remained stable over the follow-up period. Follow-up biopsies in the HCQ-treated group showed stability or improvement of the Oxford score. No complications of HCQ were documented.

In this first pediatric cohort reporting on real-life experience with HCQ, HCQ use was associated with a sustained reduction in proteinuria and stable kidney function in children with difficult-to-control cIgAN, with an excellent safety profile. Although causality cannot be inferred due to the observational design and concomitant therapies, these findings support further prospective evaluation of HCQ as a safe adjunctive treatment in selected cases of cIgAN.