Pilot Trial of Hydroxychloroquine as Add-On Therapy in Patients With Membranous Nephropathy

Abstract

Introduction: Kidney Disease Improving Global Outcomes guidelines indicate that glucocorticoids and immunosuppressants comprise the first therapeutic regimens after 4 to 6 months of treatment for high-risk primary membranous nephropathy (PMN). However, some patients cannot achieve complete or partial remission at 6 months. This study aimed to evaluate the efficacy of traditional immunotherapy combined with hydroxychloroquine (HCQ), a well-known immune regulator, in patients with PMN.

Methods: This was a single-center, open-label, prospective study. We recruited 72 patients with nephrotic syndrome and PMN proven by renal biopsy from May 2020 to June 2024. We compared changes in proteinuria, serum albumin levels, estimated glomerular filtration rate (eGFR), and relapse rate at 3, 6, 9, and 12 months follow-up in 41 patients who received glucocorticoid and immunosuppressant, and in 31 who received HCQ plus standard-of-care.

Results: Baseline characteristics showed no statistical significance between the 2 groups. However, the HCQ group showed significantly reduced proteinuria compared to standard-of-care group. A reduced proteinuria was seen at 6 months (1.2 [0.4-2.2] vs. 2.2 [1.0-3.8] g/d, P = 0.029) and the relapse rate with 12 months follow-up was also significantly decreased in the HCQ group compared to the standard-of-care group (3.7% vs. 23.3%, P = 0.033).

Conclusions: HCQ may serve as an effective add-on therapy for PMN.

Keywords: add-on therapy; glucocorticoid; hydroxychloroquine; immunosuppressants; primary membranous nephropathy.

Graphical abstract

Figure 1

Flow diagram of the trial evaluating the effect of hydroxychloroquine in patients with membranous nephropathy. AKI, acute kidney injury; GC, glucocorticoid; HCQ, hydroxychloroquine; IM, immunosuppressant; LN, lupus nephritis; MN, membranous nephropathy; PMN, primary membranous nephropathy; UPRO, urinary protein.

Figure 2

Effects of HCQ add-on therapy on PMN with 6 months follow-up. (a) 24-hour urinary protein excretion. (b) Temporal change magnitude of proteinuria decreases after the treatment. (c) Level of eGFR. (d) Changes in eGFR. (e) Levels of serum albumin. eGFR, estimated glomerular filtration rate; GC, glucocorticoid; HCQ, hydroxychloroquine; IM, immunosuppressant. ∗P < 0.05, GC + IM group versus GC + IM + HCQ group.

Figure 3

Changes in the rate of anti-PLA2R antibody positivity after 6 months of HCQ treatment. The positive rate of anti-PLA2R antibody was approximately 80% before treatment. Then the positive rate gradually decreased at 3 and 6 months following the treatment. GC + IM + HCQ group showed a lower trend compared to GC + IM and the lowest level in HCQ add-on group at 6 month after the treatment. GC, glucocorticoid; HCQ, hydroxychloroquine; IM, immunosuppressant.

Figure 4

Relapse rate of nephrotic syndrome in 2 groups at 12 months of follow-up. The recurrence rate in the GC + IM + HCQ group was significantly decreased than GC + IM group at 12 months follow-up period. ∗P < 0.05, GC + IM + HCQ group versus GC + IM group. GC, glucocorticoid; HCQ, hydroxychloroquine; IM, immunosuppressant.