Yan-Jiao Cheng1,2,3,4, Xu-Yang Cheng5,6,7,8, Yi-Miao Zhang1,2,3,4, Fang Wang1,2,3,4, Xin Wang1,2,3,4, Li-Qiang Meng1,2,3,4, Gang Liu1,2,3,4, Zhao Cui9,10,11,12, Ming-Hui Zhao1,2,3,4,13. 1. Renal Division, Peking University First Hospital, Beijing, 100034, People's Republic of China. 2. Institute of Nephrology, Peking University, Beijing, People's Republic of China. 3. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China. 4. Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, People's Republic of China. 5. Renal Division, Peking University First Hospital, Beijing, 100034, People's Republic of China. 03988@pkufh.cn. 6. Institute of Nephrology, Peking University, Beijing, People's Republic of China. 03988@pkufh.cn. 7. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China. 03988@pkufh.cn. 8. Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, People's Republic of China. 03988@pkufh.cn. 9. Renal Division, Peking University First Hospital, Beijing, 100034, People's Republic of China. cuizhao@bjmu.edu.cn. 10. Institute of Nephrology, Peking University, Beijing, People's Republic of China. cuizhao@bjmu.edu.cn. 11. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China. cuizhao@bjmu.edu.cn. 12. Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, People's Republic of China. cuizhao@bjmu.edu.cn. 13. Peking-Tsinghua Center for Life Sciences, Beijing, 100871, People's Republic of China.
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.
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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