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Effects of hydroxychloroquine on proteinuria in membranous nephropathy

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Abstract

Background

Many patients with primary membranous nephropathy have severe proteinuria unresponsive to optimized renin–angiotensin–aldosterone system inhibitors (RAASi). We evaluated the efficacy and safety of hydroxychloroquine as an adjunctive agent in membranous nephropathy (MN) treatments.

Methods

We prospectively recruited 126 patients with biopsy-proven primary membranous nephropathy and urinary protein 1–8 g/day while receiving optimized RAASi treatment for ≥ 3 months and well-controlled blood pressure. Forty-three patients received hydroxychloroquine and RAASi (hydroxychloroquine-RAASi group), and 83 patients received RAASi alone (RAASi group). Treatment responses, including proteinuria reduction, complete and partial remission rates, and autoantibody against phospholipase A2 receptor (anti-PLA2R) levels, were compared between the two groups at 6 months and over the long term.

Results

At 6 months, the effective response rate (proteinuria reduction > 30%) (57.5% vs. 28.9%, P = 0.002), clinical remission rate (35.0% vs. 15.7%, P = 0.015), and percentage change in proteinuria (− 51.7% vs. − 21.9%, P < 0.001) were higher, and the rate of switching to immunosuppressants (25.0% vs. 45.8%, P = 0.027) was lower in the hydroxychloroquine-RAASi group than in the RAASi group. Hydroxychloroquine administration was an independent protective factor with an effective response (OR 0.37, P = 0.021). In the long term, the clinical remission rate was higher in the HCQ-RAASi group (62.5% vs. 38.6%, P = 0.013). Hydroxychloroquine therapy was associated with a higher rate of anti-PLA2R reduction (< 20 U/ml) (HR 0.28, P = 0.031). We observed no serious adverse events associated with hydroxychloroquine.

Conclusions

Hydroxychloroquine could be an option for patients with membranous nephropathy seeking to achieve proteinuria reduction and anti-PLA2R antibody reduction in addition to optimized RAASi. Randomized controlled trials are needed to confirm these findings.

Trial registration

ChiCTR2100045947, 20210430, retrospectively registered.

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Availability of data and material

The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

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Acknowledgements

The technical support from Jin-ying Wang is greatly appreciated. This work was supported by grants from the Natural Science Foundation of China (81870486, 82070732, and 82090021).

Funding

Natural Science Foundation of China (81870486, 82070732, and 82090021).

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Authors and Affiliations

  1. Renal Division, Peking University First Hospital, Beijing, 100034, People’s Republic of China

    Yan-jiao Cheng, Xu-yang Cheng, Yi-miao Zhang, Fang Wang, Xin Wang, Li-qiang Meng, Gang Liu, Zhao Cui & Ming-hui Zhao

  2. Institute of Nephrology, Peking University, Beijing, People’s Republic of China

    Yan-jiao Cheng, Xu-yang Cheng, Yi-miao Zhang, Fang Wang, Xin Wang, Li-qiang Meng, Gang Liu, Zhao Cui & Ming-hui Zhao

  3. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People’s Republic of China

    Yan-jiao Cheng, Xu-yang Cheng, Yi-miao Zhang, Fang Wang, Xin Wang, Li-qiang Meng, Gang Liu, Zhao Cui & Ming-hui Zhao

  4. Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, People’s Republic of China

    Yan-jiao Cheng, Xu-yang Cheng, Yi-miao Zhang, Fang Wang, Xin Wang, Li-qiang Meng, Gang Liu, Zhao Cui & Ming-hui Zhao

  5. Peking-Tsinghua Center for Life Sciences, Beijing, 100871, People’s Republic of China

    Ming-hui Zhao

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  1. Yan-jiao Cheng
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Contributions

Research idea and study design: ZC and X-YC; data acquisition: X-YC and Y-JC; data analysis/interpretation and statistical analysis: Y-JC; supervision and mentorship: M-HZ. Each author contributed important intellectual content during the drafting and revision of the manuscript and has accepted responsibility for the overall work by ensuring that any questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. ZC takes responsibility for the following: that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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Correspondence to Xu-yang Cheng or Zhao Cui.

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Cheng, Yj., Cheng, Xy., Zhang, Ym. et al. Effects of hydroxychloroquine on proteinuria in membranous nephropathy. J Nephrol 35, 1145–1157 (2022). https://doi.org/10.1007/s40620-021-01182-z

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