Effects of hydroxychloroquine on proteinuria in membranous nephropathy.

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.

• Authors: Yan-Jiao Cheng, Xu-Yang Cheng, Yi-Miao Zhang, Fang Wang, Xin Wang, Li-Qiang Meng, Gang Liu, Zhao Cui, Ming-Hui Zhao
• Journal: Journal of nephrology (J Nephrol) Vol. 35 Issue 4 Pg. 1145-1157 (05 2022) ISSN: 1724-6059 [Electronic] Italy
• PMID: 34846713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. Italian Society of Nephrology.

Chemical References

• Autoantibodies
• Immunosuppressive Agents
• Receptors, Phospholipase A2
• Hydroxychloroquine

Topics

• Autoantibodies
• Female
• Glomerulonephritis, Membranous (complications, diagnosis, drug therapy)
• Humans
• Hydroxychloroquine (adverse effects)
• Immunosuppressive Agents (therapeutic use)
• Male
• Proteinuria (drug therapy, etiology)
• Receptors, Phospholipase A2