Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial

Rationale & Objective: Despite optimization of renin-angiotensin-aldosterone system (RAAS) inhibition, patients with immunoglobulin A nephropathy (IgAN) and persistent proteinuria remain at risk for kidney failure. We evaluated the efficacy and safety of hydroxychloroquine (HCQ), an immunomodulator, when added to the treatment regimen of patients with IgAN. Study Design: Double-blind, randomized, placebo-controlled, phase 2 clinical trial. Setting & Participants: Participants had IgAN (proteinuria with protein excretion of 0.75-3.5 g/d and estimated glomerular filtration rate > 30 mL/min/1.73 m(2)) and were receiving optimized RAAS inhibitor therapy. Interventions: Patients were randomly assigned 1:1 to receive daily oral HCQ or a placebo for 6 months. Outcomes: The primary outcome was percentage change in proteinuria between baseline and 6 months. Results: 60 participants (mean estimated glomerular filtration rate, 53.8 mUmin/1.73 m(2); median urine protein excretion, 1.7 g/d) were recruited and randomly assigned to receive HCQ n = 30) or placebo (n = 30). Percentage change in proteinuria at 6 months was significantly different between the HCQ group and the placebo group (-48.4% [IQR, -64.2%, -30.5%] vs 10.0% [IQR, -38.7% 30.6%]; P < 0.001, respectively). At 6 months, median proteinuria level was significantly lower in the HCQ group than in the placebo group (0.9 [IQR, 0.6, 1.0] g/d vs 1.9 [IQR, 0.9, 2.6] g/d; P = 0.002, respectively). No serious adverse events were recorded during the study in either study group. Limitations: The short treatment period and lack of postwithdrawal observations limit conclusions about long-term renoprotective efficacy and safety. Conclusions: HCQ in addition to optimized RAAS inhibition significantly reduced proteinuria in patients with IgAN over 6 months without evidence of adverse events. These findings require confirmation in larger treatment trials.