The efficacy and safety of hydroxychloroquine versus leflunomide in patients with IgA nephropathy: a single-center experience

Purpose To date, our understanding of IgA nephropathy (IgAN) pathophysiology has remained incomplete; therefore, treatment remains largely empiric, and the efficacy and safety of immunosuppressants remain controversial.

We aimed to assess the efficacy and safety of hydroxychloroquine and leflunomide therapy in a retrospective cohort of patients with IgAN.

Methods We screened the IgAN registration database in our department, and a total of 159 kidney patients with biopsy-confirmed IgAN were enrolled, with 57 patients receiving hydroxychloroquine plus a renin-angiotensin system inhibitor (hydroxychloroquine group), 52 patients receiving leflunomide plus a renin-angiotensin system inhibitor (leflunomide group), and 50 patients receiving only a renin-angiotensin system inhibitor (renin-angiotensin system inhibitor-only group).

Changes in proteinuria, hematuria, and the estimated glomerular filtration rate (eGFR), as well as adverse events, were analyzed during the follow-up period.

Results At the end of 6-month follow-up, proteinuria significantly decreased by 70.36 (57.54, 79.33)%, 57.29 (46.79, 67.29)% and 41.20 (25.76, 48.94)% in the hydroxychloroquine, leflunomide and renin-angiotensin system inhibitor-only groups, respectively, compared to baseline (all P values < 0.001).

Hematuria significantly decreased by 71.07 (56.48, 82.47)% in the leflunomide group ( P  < 0.001).

The eGFR improved by 3.72 ± 2.97%, 3.16 ± 2.00% and 1.91 ± 2.41%, respectively, in the hydroxychloroquine, leflunomide and renin-angiotensin system inhibitor-only groups, but without statistical significance.

No serious adverse events occurred during the follow-up period.

Conclusion Both hydroxychloroquine combined with a renin-angiotensin system inhibitor and leflunomide combined with a renin-angiotensin system inhibitor were more effective than a renin-angiotensin system inhibitor alone in improving proteinuria in IgAN patients.

Hydroxychloroquine was more effective in reducing proteinuria, and leflunomide showed superiority in reducing hematuria.

Our results need to be verified in large-scale randomized controlled trials.

Graphical abstract