• Li-Jun Liu, Ya-Zi Yang, Su-Fang Shi, Yun-Fei Bao, Chao Yang, Sai-Nan Zhu, Gui-Li Sui, Yu-Qing Chen, Ji-Cheng Lv, and Hong Zhang.
• Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China. Electronic address: lijun.liu@aliyun.com.
• Am. J. Kidney Dis. 2019 Jul 1; 74 (1): 15-22.

Rationale & ObjectiveDespite 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 DesignDouble-blind, randomized, placebo-controlled, phase 2 clinical trial.Setting & ParticipantsParticipants had IgAN (proteinuria with protein excretion of 0.75-3.5g/d and estimated glomerular filtration rate>30mL/min/1.73m2) and were receiving optimized RAAS inhibitor therapy.InterventionsPatients were randomly assigned 1:1 to receive daily oral HCQ or a placebo for 6 months.OutcomesThe primary outcome was percentage change in proteinuria between baseline and 6 months.Results60 participants (mean estimated glomerular filtration rate, 53.8mL/min/1.73m2; median urine protein excretion, 1.7g/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.LimitationsThe short treatment period and lack of postwithdrawal observations limit conclusions about long-term renoprotective efficacy and safety.ConclusionsHCQ 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.FundingThis study was supported by grants from a government entity, the Capital of Clinical Characteristics, and the Applied Research Fund.Trial RegistrationRegistered at ClinicalTrials.gov with study number NCT02942381.Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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