Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial
Abstract Background Calcineurin inhibitors, such as cyclosporine, are primary treatments for membranous nephropathy (MN). Optimizing this regimen is crucial to reduce nephrotoxicity and enhance immunological remission. Sirolimus, when combined with cyclosporine, may offer non-inferior clinical remis...
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2025-05-01
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| Online Access: | https://doi.org/10.1186/s12916-025-04173-0 |
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| author | Fang Wang Chao Yang Yue Shu Cai-xia Lin Yao Yao Yue Li Yi-miao Zhang Xin Wang Li-qiang Meng Xu-yang Cheng Gang Liu Ming-hui Zhao Zhao Cui |
| author_facet | Fang Wang Chao Yang Yue Shu Cai-xia Lin Yao Yao Yue Li Yi-miao Zhang Xin Wang Li-qiang Meng Xu-yang Cheng Gang Liu Ming-hui Zhao Zhao Cui |
| author_sort | Fang Wang |
| collection | DOAJ |
| description | Abstract Background Calcineurin inhibitors, such as cyclosporine, are primary treatments for membranous nephropathy (MN). Optimizing this regimen is crucial to reduce nephrotoxicity and enhance immunological remission. Sirolimus, when combined with cyclosporine, may offer non-inferior clinical remission to cyclosporine monotherapy, while improving kidney function preservation and antibody clearance. Methods This single-center, randomized controlled, phase 2 clinical trial involved 74 patients with biopsy-proven primary MN and persistent proteinuria > 3.5 g/d, despite 6 months of supportive care. Participants were randomly assigned (1:1) to receive either sirolimus plus cyclosporine or cyclosporine monotherapy for 12 months. Results At 12 months, composite remission was achieved in 26 of 36 patients (72%) receiving combination therapy and in 24 of 36 (67%) receiving cyclosporine alone (95% confidence interval for noninferiority: 0.48—3.56). Immunological remission, defined as anti-phospholipase A2 receptor antibody conversion from positive to negative, was significantly higher in the combination group (70% vs. 20%, P < 0.001) at 6 months. Moreover, eGFR decline was significantly attenuated in the combination group (ΔeGFR: -7.1 vs. -21.3 ml/min/1.73m2, P < 0.001) at 12 months. One serious adverse event occurred in the combination group, compared to none in the monotherapy group (P = 0.317). Conclusions Sirolimus combined with cyclosporine was noninferior to cyclosporine monotherapy in achieving clinical remission in MN and demonstrated superior benefits in immunological remission and kidney function preservation. |
| format | Article |
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| institution | DOAJ |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj-art-dd3d4ad59cf64149a5ba135eefe437c92025-08-20T03:16:40ZengBMCBMC Medicine1741-70152025-05-0123111110.1186/s12916-025-04173-0Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trialFang Wang0Chao Yang1Yue Shu2Cai-xia Lin3Yao Yao4Yue Li5Yi-miao Zhang6Xin Wang7Li-qiang Meng8Xu-yang Cheng9Gang Liu10Ming-hui Zhao11Zhao Cui12Renal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalRenal Division, Peking University First HospitalAbstract Background Calcineurin inhibitors, such as cyclosporine, are primary treatments for membranous nephropathy (MN). Optimizing this regimen is crucial to reduce nephrotoxicity and enhance immunological remission. Sirolimus, when combined with cyclosporine, may offer non-inferior clinical remission to cyclosporine monotherapy, while improving kidney function preservation and antibody clearance. Methods This single-center, randomized controlled, phase 2 clinical trial involved 74 patients with biopsy-proven primary MN and persistent proteinuria > 3.5 g/d, despite 6 months of supportive care. Participants were randomly assigned (1:1) to receive either sirolimus plus cyclosporine or cyclosporine monotherapy for 12 months. Results At 12 months, composite remission was achieved in 26 of 36 patients (72%) receiving combination therapy and in 24 of 36 (67%) receiving cyclosporine alone (95% confidence interval for noninferiority: 0.48—3.56). Immunological remission, defined as anti-phospholipase A2 receptor antibody conversion from positive to negative, was significantly higher in the combination group (70% vs. 20%, P < 0.001) at 6 months. Moreover, eGFR decline was significantly attenuated in the combination group (ΔeGFR: -7.1 vs. -21.3 ml/min/1.73m2, P < 0.001) at 12 months. One serious adverse event occurred in the combination group, compared to none in the monotherapy group (P = 0.317). Conclusions Sirolimus combined with cyclosporine was noninferior to cyclosporine monotherapy in achieving clinical remission in MN and demonstrated superior benefits in immunological remission and kidney function preservation.https://doi.org/10.1186/s12916-025-04173-0CyclosporineSirolimusMembranous NephropathyClinical TrialAnti-PLA2R Antibody |
| spellingShingle | Fang Wang Chao Yang Yue Shu Cai-xia Lin Yao Yao Yue Li Yi-miao Zhang Xin Wang Li-qiang Meng Xu-yang Cheng Gang Liu Ming-hui Zhao Zhao Cui Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial BMC Medicine Cyclosporine Sirolimus Membranous Nephropathy Clinical Trial Anti-PLA2R Antibody |
| title | Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial |
| title_full | Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial |
| title_fullStr | Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial |
| title_full_unstemmed | Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial |
| title_short | Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial |
| title_sort | safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy a randomized controlled trial |
| topic | Cyclosporine Sirolimus Membranous Nephropathy Clinical Trial Anti-PLA2R Antibody |
| url | https://doi.org/10.1186/s12916-025-04173-0 |
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