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Lu L, Cai S, Zhu H, Liu G, Wang Y, Ren P, Lan L, Shen X, Chen L, Xu Y, Cheng J, Li X, Chen J, Han F. Comparations of efficacy and safety of rituximab, calcineurin inhibitors and cyclophosphamide in primary membranous nephropathy: a single-center retrospective analysis. BMC Nephrol 2024; 25:473. [PMID: 39719585 DOI: 10.1186/s12882-024-03912-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 12/10/2024] [Indexed: 12/26/2024] Open
Abstract
BACKGROUND To compare the efficacy and safety of rituximab (RTX), calcineurin inhibitor (CNI) and cyclophosphamide (CTX) plus glucocorticoids in the treatment of primary membranous nephropathy (PMN). METHODS Totally 478 biopsy-proven PMN patients in single center were retrospectively included. After 1:1 propensity score matching (PSM), 258 patients were included in RTX, CNI or CTX group (86 patients in each group). RESULTS After PSM, there were no differences on serum creatinine, eGFR, serum albumin, urine protein, anti-PLA2R antibody levels among groups. The follow-up duration was 12 (10.5, 18) months in CNI group, 12 (12, 18) months in CTX group and 12 (12, 18) months in RTX group. Throughout entire follow-up period, 39 patients (45.3%) in CNI group, 47 patients (54.7%) in CTX group, and 59 patients (68.6%) in RTX group achieved total remission (TR, either complete remission or partial remission). The survival curve showed a higher rate of TR in RTX group than CNI group (p = 0.018). A relapse occurred in 15 of 39 (38.5%) patients in CNI group, significantly higher than CTX group (4.3%, p < 0.001) and RTX group (3.4%, p < 0.001). In CNI group, 36% patients had a ≥ 25% decline in eGFR. CONCLUSIONS RTX may be more effective than CNI in inducing remission in PMN and showed similar efficacy to CTX. CNI may have a high risk of proteinuria relapse and eGFR decline.
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Affiliation(s)
- Luying Lu
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shasha Cai
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Nephrology, The First People's Hospital of Wenling, Taizhou, China
| | - Huayan Zhu
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Nephrology, The First People's Hospital of Huzhou, Huzhou, China
| | - Guangjun Liu
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yaomin Wang
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Pingping Ren
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lan Lan
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoqi Shen
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Liangliang Chen
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Xu
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun Cheng
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiayu Li
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianghua Chen
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Fei Han
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Feng C, Chen X, Wang X, Guo M, Guo Z. Efficacy and safety of glucocorticoid combined with cyclophosphamide therapy on membranous nephropathy: a systematic review and meta-analysis. Front Pharmacol 2024; 15:1480638. [PMID: 39664513 PMCID: PMC11631627 DOI: 10.3389/fphar.2024.1480638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/14/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND This review systematically evaluates the efficacy and safety of the combined treatment of glucocorticoids (GC) and cyclophosphamide (CTX) in patients with membranous nephropathy (MN). METHODS As of June 2024, a comprehensive literature search was performed utilizing several reputable databases, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang. A meta-analysis was then carried out using Review Manager 5.4 and STATA/SE-15 software. RESULTS This research evaluated a total of 22 articles involving 1,971 patients. The findings revealed that patients with MN receiving combined GC and CTX therapy had significantly higher complete remission rates (odds ratio = 1.78, p = 0.02) and total remission rates (odds ratio = 2.14, p = 0.01) when the follow-up period exceeded 12 months. Additionally, this treatment demonstrated greater efficacy in lowering serum creatinine levels compared to the control group (standardized mean difference = -0.19, p = 0.04), while its relapse rate was also lower than that of the control group (odds ratio = 0.51, p = 0.009). However, it has a high incidence of serious adverse effects (odds ratio = 2.32, p = 0.03). CONCLUSION Our systematic review highlights that the combination of GC and CTX demonstrates superior long-term effectiveness and reduced relapse rates in managing membranous nephropathy (MN). Furthermore, this drug combination is considered the optimal choice for normalizing serum creatinine levels. Data on the effectiveness and safety of glucocorticoids alone versus other drugs alone, and the treatment of secondary membranous nephropathy (SMN), are limited. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=566477, identifier CRD42024566477.
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Affiliation(s)
- Chengcheng Feng
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Xuexun Chen
- Department of Nephrology, School of Clinical Medicine, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang, China
| | - Xiangming Wang
- Department of Nephrology, School of Clinical Medicine, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang, China
| | - Min Guo
- Department of Nephrology, School of Clinical Medicine, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang, China
| | - Zhentao Guo
- Department of Nephrology, School of Clinical Medicine, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang, China
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Rui M, Jiang L, Pan JJ, Huang XT, Cui JF, Zhang SJ, He SM, Han HH, Chen X, Wang DD. Effects of tacrolimus on proteinuria in Chinese and Indian patients with idiopathic membranous nephropathy: the results of machine learning study. Int Urol Nephrol 2024; 56:3047-3055. [PMID: 38642210 DOI: 10.1007/s11255-024-04056-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 04/08/2024] [Indexed: 04/22/2024]
Abstract
PURPOSE The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method. METHODS The Emax model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with Emax model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4-10 ng/ml. RESULTS In machine learning model, the Emax from tacrolimus effecting proteinuria in IMN patients was -72.7%, the ET50 was 0.43 months, and the time to achieving 25% Emax, 50% Emax, 75% Emax, and 80% (plateau) Emax of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively. CONCLUSION For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4-10 ng/ml for at least 1.72 months.
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Affiliation(s)
- Min Rui
- Department of Orthopaedics, The Affiliated Jiangyin Clinical College of Xuzhou Medical University, Jiangyin, 214400, Jiangsu, China
| | - Lei Jiang
- Department of Pharmacy, Taixing People's Hospital, Taixing, 225400, Jiangsu, China
| | - Jia-Jun Pan
- Department of Thoracic Cardiovascular Surgery, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221100, Jiangsu, China
| | - Xue-Ting Huang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Jia-Fang Cui
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Shi-Jia Zhang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Su-Mei He
- Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215153, Jiangsu, China.
| | - Huan-Huan Han
- Department of Pharmacy, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222000, Jiangsu, China.
| | - Xiao Chen
- School of Nursing, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
| | - Dong-Dong Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
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Ang JF, Widjanarko ND, Ekaputra A. Rituximab versus tacrolimus as corticosteroid-sparing therapy for children with steroid-dependent nephrotic syndrome: A systematic review and meta-analysis of randomized and nonrandomized controlled trials. Tzu Chi Med J 2024; 36:319-329. [PMID: 38993828 PMCID: PMC11236076 DOI: 10.4103/tcmj.tcmj_234_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 10/16/2023] [Accepted: 11/09/2023] [Indexed: 07/13/2024] Open
Abstract
Objectives Prolonged use of corticosteroids induced complicated course in children with steroid-dependent nephrotic syndrome (SDNS), and the use of tacrolimus, a first-line alternative calcineurin inhibitor (CNI) agent was related to some unwanted adverse effects. Rituximab, a second alternative treatment has been proven to reliably reduce the number of relapses within 12 months with minimal adverse effects. Materials and Methods Our review follows Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. All the databases were derived from MEDLINE, Proquest, EBSCOhost, Wiley, and Google Scholar within the past 11 years. The risk of bias was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions. Meta-analysis used Review Manager (version 5.4) with a random effect model to obtain a pooled mean difference (MD) and odds ratio with 95% confidence intervals (CIs). Results Four studies were included based on our eligibility criteria, and only three were included in the quantitative analysis. Three studies had low and one study had a moderate risk of bias. Pooled data results indicated that Rituximab was superior to tacrolimus in reducing the number of patients with 1-2 relapses (MD = 0.44, [95% CI: 0.21-0.91]) and had higher eGFR values (MD = 6.67; [CI - 2.92-10.61]). However, Rituximab showed insignificant superiority compared to tacrolimus in reducing the number of patients with 3 relapses, sustained remission, cumulative steroid use, serum cholesterol, and serum albumin concentrations. Conclusion Rituximab exhibits more advantages in treating SDNS compared to tacrolimus, although the treatment options are highly individualized. Both regimens must also be weighed against their potential side effects to achieve a better overall health status.
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Affiliation(s)
- Jessica Felicia Ang
- Department of General Medicine, Faculty of Medicine, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
| | - Nicolas Daniel Widjanarko
- Department of General Medicine, Faculty of Medicine, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
| | - Anthony Ekaputra
- Department of General Medicine, Faculty of Medicine, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
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Zhang X, Dou J, Gao G, Sheng X, Shen Y, Feng Y, Wu X, Zhang Z, Cheng G. Comparison of tacrolimus with or without prednisone therapy in primary membranous nephropathy: a retrospective clinical study. Sci Rep 2024; 14:14214. [PMID: 38902302 PMCID: PMC11190188 DOI: 10.1038/s41598-024-64661-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 06/11/2024] [Indexed: 06/22/2024] Open
Abstract
Previous studies showed tacrolimus monotherapy and dual therapy with tacrolimus and prednisone as effective treatment modalities in managing membranous nephropathy. However, few studies have compared these therapeutic regimens. The patients were divided into two groups based on the treatment regimen: (1) tacrolimus and prednisone dual therapy (T + P group, n = 67) treatment group; and (2) tacrolimus monotherapy (T group, n = 65) or the control group. Propensity matching method and subgroup analysis to eliminate the bias in the relationship between the treatment regimen and the outcomes. The mean remission times were 20.33 ± 2.75 weeks at T group and 9.50 ± 1.81 weeks at T + P group. The T group had a remission rates of 73.33, 76.66 and 66.66% at 12weeks, 24weeks and 48weeks, while the T + P group had a remission rate of 81.66, 86.66, 91.66%; At the follow-up of 48 weeks, the relapse rate for the T group was 21.66%, and that for the T + P group was 5%. The anti-PLA2R ab is positive and therapy may be the independent risk factors for predicting remission. Tacrolimus and low-dose prednisone dual therapy is efficacious in managing MN and lowers the recurrence rate in clinical practice.
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Affiliation(s)
- Xinyue Zhang
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jingyu Dou
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ge Gao
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaoxiao Sheng
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ya Shen
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuhua Feng
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xueying Wu
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhen Zhang
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Genyang Cheng
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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Zhang YP, Ran L, Guo L, Gou YL, Guo SS, Xu Y, Hua X, Chen H. Efficacy of tacrolimus monotherapy in primary membranous nephropathy. Open Med (Wars) 2024; 19:20240957. [PMID: 38841175 PMCID: PMC11151391 DOI: 10.1515/med-2024-0957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 03/24/2024] [Accepted: 03/27/2024] [Indexed: 06/07/2024] Open
Abstract
Objective The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC). Methods This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05-0.075 mg/kg/day) or 36 received TAC (0.05-0.075 mg/kg/day) and GC (0.3-0.5 mg/kg/day of prednisone). Results At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar (P > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups (P > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant (P < 0.05). Conclusion TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.
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Affiliation(s)
- Ya-pu Zhang
- Department of Nephrology, Affiliated Hospital of Hebei University, Lianchi District, Baoding, 071000, Hebei, China
| | - Lei Ran
- Department of Nephrology, Affiliated Hospital of Hebei University, Lianchi District, Baoding, 071000, Hebei, China
| | - Li Guo
- Department of Nephrology, Affiliated Hospital of Hebei University, Lianchi District, Baoding, 071000, Hebei, China
| | - Yan-Li Gou
- Department of Nephrology, Affiliated Hospital of Hebei University, Lianchi District, Baoding, 071000, Hebei, China
| | - Shan-shan Guo
- Department of Nephrology, Affiliated Hospital of Hebei University, Lianchi District, Baoding, 071000, Hebei, China
| | - Yang Xu
- Department of Nephrology, Affiliated Hospital of Hebei University, Lianchi District, Baoding, 071000, Hebei, China
| | - Xin Hua
- The Sixth Medical Center of Pla General Hospital, Haidian District, Beijing, China
| | - Hang Chen
- Department of Nephrology, Affiliated Hospital of Hebei University, Lianchi District, Baoding, 071000, Hebei, China
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Wei X, Long M, Fan Z, Hou Y, Zhu X, Qu Z, Du Y. Prediction of immunotherapy response in idiopathic membranous nephropathy using deep learning-pathological and clinical factors. Front Endocrinol (Lausanne) 2024; 15:1328579. [PMID: 38524629 PMCID: PMC10958378 DOI: 10.3389/fendo.2024.1328579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 02/26/2024] [Indexed: 03/26/2024] Open
Abstract
Background Owing to individual heterogeneity, patients with idiopathic membranous nephropathy (IMN) exhibit varying sensitivities to immunotherapy. This study aimed to establish and validate a model incorporating pathological and clinical features using deep learning training to evaluate the response of patients with IMN to immunosuppressive therapy. Methods The 291 patients were randomly categorized into training (n = 219) and validation (n = 72) cohorts. Patch-level convolutional neural network training in a weakly supervised manner was utilized to analyze whole-slide histopathological features. We developed a machine-learning model to assess the predictive value of pathological signatures compared to clinical factors. The performance levels of the models were evaluated using the area under the receiver operating characteristic curve (AUC) on the training and validation tests, and the prediction accuracies of the models for immunotherapy response were compared. Results Multivariate analysis indicated that diabetes and smoking were independent risk factors affecting the response to immunotherapy in IMN patients. The model integrating pathologic features had a favorable predictive value for determining the response to immunotherapy in IMN patients, with AUCs of 0.85 and 0.77 when employed in the training and test cohorts, respectively. However, when incorporating clinical features into the model, the predictive efficacy diminishes, as evidenced by lower AUC values of 0.75 and 0.62 on the training and testing cohorts, respectively. Conclusions The model incorporating pathological signatures demonstrated a superior predictive ability for determining the response to immunosuppressive therapy in IMN patients compared to the integration of clinical factors.
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Affiliation(s)
| | | | | | | | | | - Zhihui Qu
- *Correspondence: Zhihui Qu, ; Yujun Du,
| | - Yujun Du
- *Correspondence: Zhihui Qu, ; Yujun Du,
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Li Y, Gao Z, Zhu J, Su J, Chen P, Li J, Feng M. Comparison of Dosage of Glucocorticoid in Idiopathic Membranous Nephropathy: A Systematic Review and Network Meta-Analysis. Cureus 2024; 16:e51936. [PMID: 38333440 PMCID: PMC10851919 DOI: 10.7759/cureus.51936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2024] [Indexed: 02/10/2024] Open
Abstract
PURPOSE Idiopathic membranous nephropathy (IMN) with moderate risk or above was recommended to receive immunosuppressive therapy. We attempted to evaluate the optimal dose of glucocorticoid when combined with evidence-proven effective immunosuppressants by network meta-analysis. METHODS A systematic review of the literature was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until January 2022. Randomized controlled trials (RCTs) in IMN limited to supportive care, glucocorticoids, cyclophosphamide, chlorambucil, calcineurin inhibitors (CNIs), and rituximab were screened. RESULTS Twenty-eight RCTs of 1,830 patients were included. Therapeutic regimens were divided as follows: moderate- to high-dose glucocorticoids plus CNIs (HMSCn), moderate- to high-dose glucocorticoids plus cyclophosphamide (HMSCt), moderate- to high-dose glucocorticoids plus chlorambucil (HMSCh), zero- to low-dose glucocorticoids plus CNIs (LNSCn), zero- to low-dose glucocorticoids plus cyclophosphamide (LNSCt), rituximab alone (R), glucocorticoids alone (SE), and supportive care alone (SP). Compared with SP, HMSCh (risk ratio [RR]: 1.77, 95% confidence interval [CI]: 1, 3.18), HMSCn (RR: 2.5, 95%CI: 1.25, 5.11), HMSCt (RR: 2.15, 95%CI: 1.29, 3.64), LNSCn (RR: 2.16, 95%CI: 1.25, 3.95), and R (RR: 2.07, 95%CI: 1, 4.39) had a higher probability of total remission rate, while HMSCn represented the highest probability depending on the surface under the cumulative ranking area (SUCRA) ranking values. Regarding infection, no significant difference was found between different doses of glucocorticoids plus the same immunosuppressant. HMSCn and HMSCt showed superiority in reducing 24-hour urine total protein compared with HMSCh, LNSCn, SE, and SP, while HMSCn seemed to be the most effective regimen through the ranking of SUCRA value. CONCLUSION Moderate- to high-dose glucocorticoids showed superiority in proteinuria remission when combined with CNIs in IMN, with no increasing risk of infection.
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Affiliation(s)
- Yanhua Li
- Department of Rheumatology, Nanhai District People's Hospital, Foshan, CHN
| | - Ziqing Gao
- Department of Nephrology, Sun Yat-sen Memorial Hospital, Guangzhou, CHN
| | - Jianhong Zhu
- Department of Pharmacy, Sun Yat-sen Memorial Hospital, Guangzhou, CHN
| | - Jianan Su
- Department of Nephrology, Sun Yat-sen Memorial Hospital, Guangzhou, CHN
| | - Pengwei Chen
- Department of Nephrology, Sun Yat-sen Memorial Hospital, Guangzhou, CHN
| | - Jiande Li
- Department of Pain Management, The First People's Hospital of Foshan, Foshan, CHN
| | - Min Feng
- Department of Nephrology, Sun Yat-sen Memorial Hospital, Guangzhou, CHN
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Fan Z, Lei L, Su S, Zhang S, Xie N, Li L, Lu Y, Di L, Wang M, Xu M, Shen X, Da Y. Comparison between mono-tacrolimus and mono-glucocorticoid in the treatment of myasthenia gravis. Ann Clin Transl Neurol 2023; 10:589-598. [PMID: 36808840 PMCID: PMC10109324 DOI: 10.1002/acn3.51746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 02/04/2023] [Accepted: 02/07/2023] [Indexed: 02/23/2023] Open
Abstract
OBJECTIVE Use of tacrolimus in mild to moderate myasthenia gravis (MG) is generally limited to glucocorticoid-refractory cases; the advantage of mono-tacrolimus over mono-glucocorticoids is unknown. METHODS We included mild to moderate MG patients treated with mono-tacrolimus (mono-TAC) or mono-glucocorticoids (mono-GC). The correlation between the immunotherapy options and the treatment efficacy and side effects were examined in 1:1 propensity-score matching. The main outcome was time to minimal manifestations status or better (MMS or better). Secondary outcomes include time to relapse, the mean changes in Myasthenia Gravis-specific Activities of Daily Living (MG-ADL) scores and the rate of adverse events. RESULTS Baseline characteristics showed no difference between matched groups (49 matched pairs). There were no differences in median time to MMS or better between the mono-TAC group and mono-GC group (5.1 vs. 2.8 months: unadjusted hazard ratio [HR], 0.73; 95% CI, 0.46-1.16; p = 0.180), as well as in median time to relapse (data unavailable for the mono-TAC group since 44 of 49 [89.8%] participants remained in MMS or better; 39.7 months in mono-GC group: unadjusted HR, 0.67; 95% CI, 0.23-1.97; p = 0.464). Changes in MG-ADL scores between the two groups were similar (mean differences, 0.3; 95% CI, -0.4 to 1.0; p = 0.462). The rate of adverse events was lower in the mono-TAC group compared to the mono-GC group (24.5% vs. 55.1%, p = 0.002). INTERPRETATION Mono-tacrolimus performs superior tolerability with non-inferior efficacy compared to mono-glucocorticoids in mild to moderate myasthenia gravis patients who refuse or have a contraindication to glucocorticoids.
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Affiliation(s)
- Zhirong Fan
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
- Department of NeurologyXijing Hospital, Fourth Military Medical UniversityXi'anChina
| | - Lin Lei
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
- Department of NeurologyBeijing Jishuitan HospitalBeijingChina
| | - Shengyao Su
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Shu Zhang
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Nairong Xie
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Ling Li
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
- Department of NeurologyTianjin 4th Centre HospitalTianjinChina
| | - Yan Lu
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Li Di
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Min Wang
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Min Xu
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Xin‐Ming Shen
- Department of Neurology and Neuromuscular Research LaboratoryMayo ClinicRochesterMinnesotaUSA
| | - Yuwei Da
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
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Chen M, Zhang X, Xiong Y, Xu G. Efficacy of low or heavy rituximab‑based protocols and comparison with seven regimens in idiopathic membranous nephropathy: a systematic review and network meta-analysis. Int Urol Nephrol 2023; 55:641-651. [PMID: 36161550 DOI: 10.1007/s11255-022-03372-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 08/21/2022] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of rituximab for IMN are still controversial. This network meta-analysis (NMA) was conducted to compare the efficacy of different rituximab dosages and other main treatments in IMN treatment. METHODS Randomized controlled trials (RCTs) and observational studies analyzing nine therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR) and relapse rate. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. RESULTS Twelve RCTs and 12 observational studies involving 1724 patients were pooled for comparison of 9 interventions. This NMA demonstrated steroids + tacrolimus was ranked first in the aspect of total remission at 6 months (92%) and 12 months (81.3%). The total remission rate associated with tacrolimus + rituximab increased rapidly between the sixth (SUCRA 22.5%) and the twelfth month (SUCRA 63.9%). Tacrolimus and cyclosporine A were associated with higher total remission at 6 months (78.8% and 65.4%, separately) and decreased at 12 months (58.1 and 34.9%, separately). Steroids + cyclophosphamide, rituximab (Heavy dose) and rituximab (Low dose) had stable remission rates at 6 (63.7%, 46.6%, and 19.4%) and 12 months (SUCRA 66.9%, 39.6%, and 28.8%). Tacrolimus and cyclosporine A were associated with a significantly higher risk of relapse than that with steroids + cyclophosphamide, rituximab (Heavy dose), and rituximab (Low dose). CONCLUSIONS For IMN in adults, steroids + tacrolimus was ranked first in the aspect of total remission, followed by steroids + cyclophosphamide and steroids + cyclosporine A. The TR associated with rituximab (Heavy and Low dosage) at 12 months was higher than that at 6 months. And rituximab (Heavy dose) achieves a higher rate of total remission than that of rituximab (Low dose).
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Affiliation(s)
- Miaomiao Chen
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, 330006, No. 1, Minde Road, Donghu District, Nanchang, Jiangxi, China
- Grade 2018, The First Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Xuehan Zhang
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, 330006, No. 1, Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Yi Xiong
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, 330006, No. 1, Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Gaosi Xu
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, 330006, No. 1, Minde Road, Donghu District, Nanchang, Jiangxi, China.
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Bao N, Gu M, Yu X, Wang J, Gao L, Miao Z, Kong W. Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis. Open Life Sci 2023; 18:20220527. [PMID: 36694696 PMCID: PMC9835199 DOI: 10.1515/biol-2022-0527] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/23/2022] [Accepted: 11/02/2022] [Indexed: 01/11/2023] Open
Abstract
This network meta-analysis (NMA) aims to investigate the efficacy and safety of different pharmacological treatments for idiopathic membranous nephropathy (IMN). Thirty-four relevant studies were extracted from PubMed, Embase, Cochrane database, and MEDLINE. Treatment with tacrolimus (TAC), cyclophosphamide (CTX), mycophenolate mofetil, chlorambucil (CHL), cyclosporin A (CSA), steroids, rituximab (RTX), and conservative therapy were compared. Outcomes were measured using remission rate and incidence of side effects. Summary estimates were expressed as the odds ratio (OR) and 95% confidence intervals (CIs). The quality of findings was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. In the direct meta-analysis for comparison of complete remission (CR) rate, the curative effect of RTX is inferior to CTX (OR 0.37; CI 0.18, 0.75). In the NMA of CR rate, the results showed that the curative effects of CTX, CHL, and TAC were significantly higher than those of the control group. The efficacy of RTX is not inferior to the CTX (OR 0.81; CI 0.32, 2.01), and the level of evidence was moderate; CSA was not as effective as RTX, and the difference was statistically significant with moderate evidence (OR 2.98, CI 1.00, 8.91). In summary, we recommend CTX and RTX as the first-line drug for IMN treatment.
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Affiliation(s)
- Neng Bao
- Department of Nephrology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, 157 Daming Road, Nanjing City, Jiangsu, 210000, PR China
| | - Mingjia Gu
- Department of Nephrology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, 6 Huanghe Road, Changshu City, Jiangsu, 215500, PR China
| | - Xiang Yu
- Department of Nephrology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing City, Jiangsu, 210000, PR China
| | - Jin Wang
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Binhu District of Wuxi, Jiangsu, 214000, PR China
| | - Leiping Gao
- Department of Nephrology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, 6 Huanghe Road, Changshu City, Jiangsu, 215500, PR China
| | - Zhiwei Miao
- Department of Gastroenterology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, 77 Changan South Road, Zhangjiagang, 215600, PR China
| | - Wei Kong
- Department of Nephrology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, 157 Daming Road, Nanjing City, Jiangsu, 210000, PR China
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12
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Liang S, Liang YJ, Li Z, Wang Y, Guo XR, Zhang CY, Zhang C, Wu J, Wang XL, Li YS, Cai GY, Chen XM. Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients. Ther Clin Risk Manag 2023; 19:351-360. [PMID: 37077772 PMCID: PMC10106312 DOI: 10.2147/tcrm.s399218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 03/19/2023] [Indexed: 04/21/2023] Open
Abstract
Purpose Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.
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Affiliation(s)
- Shuang Liang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Yan-Jun Liang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Zhao Li
- Haikou People’s Hospital Affiliated to Xiangya School of Medicine, Haikou, People’s Republic of China
| | - Yong Wang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Xin-Ru Guo
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Chao-yang Zhang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Chun Zhang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Jie Wu
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Xiao-Long Wang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Yi-Sha Li
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
| | - Guang-Yan Cai
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
- Correspondence: Guang-Yan Cai, Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China, Tel +86 13601062936, Fax +86 010-68130297, Email
| | - Xiang-Mei Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China
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Yuan W, Sui L, Xin H, Liu M, Shi H. Discussion on machine learning technology to predict tacrolimus blood concentration in patients with nephrotic syndrome and membranous nephropathy in real-world settings. BMC Med Inform Decis Mak 2022; 22:336. [PMID: 36539772 PMCID: PMC9764593 DOI: 10.1186/s12911-022-02089-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Given its narrow treatment window, high toxicity, adverse effects, and individual differences in its use, we collected and sorted data on tacrolimus use by real patients with kidney diseases. We then used machine learning technology to predict tacrolimus blood concentration in order to provide a basis for tacrolimus dose adjustment and ensure patient safety. METHODS This study involved 913 hospitalized patients with nephrotic syndrome and membranous nephropathy treated with tacrolimus. We evaluated data related to patient demographics, laboratory tests, and combined medication. After data cleaning and feature engineering, six machine learning models were constructed, and the predictive performance of each model was evaluated via external verification. RESULTS The XGBoost model outperformed other investigated models, with a prediction accuracy of 73.33%, F-beta of 91.24%, and AUC of 0.5531. CONCLUSIONS Through this exploratory study, we could determine the ability of machine learning to predict TAC blood concentration. Although the results prove the predictive potential of machine learning to some extent, in-depth research is still needed to resolve the XGBoost model's bias towards positive class and thereby facilitate its use in real-world settings.
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Affiliation(s)
- Weijia Yuan
- grid.414252.40000 0004 1761 8894Department of Information, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Lin Sui
- grid.414252.40000 0004 1761 8894Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Haili Xin
- grid.414252.40000 0004 1761 8894Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Minchao Liu
- grid.414252.40000 0004 1761 8894Department of Information, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Huayu Shi
- grid.414252.40000 0004 1761 8894Department of Information, Medical Supplies Center of PLA General Hospital, Beijing, China
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Hemanth Kumar M, Sandhu J, Sandhu JS. Profile and primary treatment outcomes in membranous nephropathy. Saudi Med J 2022; 43:1051-1056. [PMID: 36104046 PMCID: PMC9987665 DOI: 10.15537/smj.2022.43.9.20220459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/10/2022] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVES To assess the clinical profile and primary treatment response and outcomes in idiopathic membranous nephropathy (IMN) patients. METHODS This study was carried out between December 2013 and January 2019 in a tertiary care hospital in North India on 2 years retrospective and 3 years prospective renal biopsy proven patients with IMN presenting with nephrotic syndrome. Basic baseline investigations carried out were urinary proteins, serum albumin, serum creatinine, other special tests wherever necessary or possible (including phospholipase A2 receptor antibodies), and different treatment regimens were offered for treatment. The patients were followed up for a minimum period of 6 months after administration of treatment. RESULTS The study was carried out in 120 patients with mean age of 43±14.6 years and male female ratio of 1.65:1. Hypertension was noted in 36%, microscopic hematuria in 13%, and mean 24 hours urinary proteinuria 10.5±3.1 gm. Complete or partial response at 6 months was observed in 57% and 34% cases to cyclophosphamide, 60% and 40% to modified Ponticelli treatment, 81% and 19% to tacrolimus, and 40% and 36% cases to rituximab. Relapse was observed in 6% of cyclophosphamide and 13% in tacrolimus groups. CONCLUSION Our results show a good and comparable response to cyclophosphamide, tacrolimus, and rituximab at 6 months of follow up. The cases which achieved complete remission had significantly lower baseline proteinuria compared to those who did not respond.
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Affiliation(s)
- M.K. Hemanth Kumar
- From the Department of Nephrology (Kumar, J. S. Sandhu); from the Department of Pathology (J. Sandhu), Dayanand Medical College and Hospital, from the Department of Pathology (J. Sandhu), Gian Sagar Medical College and Hospital, and from the Department of Nephrology (J. S. Sandhu), Satguru Partap Singh Hospital, Punjab, India.
| | - Jashan Sandhu
- From the Department of Nephrology (Kumar, J. S. Sandhu); from the Department of Pathology (J. Sandhu), Dayanand Medical College and Hospital, from the Department of Pathology (J. Sandhu), Gian Sagar Medical College and Hospital, and from the Department of Nephrology (J. S. Sandhu), Satguru Partap Singh Hospital, Punjab, India.
| | - Jasvinder S. Sandhu
- From the Department of Nephrology (Kumar, J. S. Sandhu); from the Department of Pathology (J. Sandhu), Dayanand Medical College and Hospital, from the Department of Pathology (J. Sandhu), Gian Sagar Medical College and Hospital, and from the Department of Nephrology (J. S. Sandhu), Satguru Partap Singh Hospital, Punjab, India.
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15
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Liu J, Li X, Huang T, Xu G. Efficacy and safety of 12 immunosuppressive agents for idiopathic membranous nephropathy in adults: A pairwise and network meta-analysis. Front Pharmacol 2022; 13:917532. [PMID: 35959430 PMCID: PMC9358043 DOI: 10.3389/fphar.2022.917532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/27/2022] [Indexed: 11/29/2022] Open
Abstract
Background: Immunosuppressants have been applied in the remedy of idiopathic membranous nephropathy (IMN) extensively. Nevertheless, the efficacy and safety of immunosuppressants do not have final conclusion. Thus, a pairwise and network meta-analysis (NMA) was carried out to seek the most recommended therapeutic schedule for patients with IMN. Methods: Randomized controlled trials (RCTs) including cyclophosphamide (CTX), mycophenolate mofetil (MMF), tacrolimus-combined mycophenolate mofetil (TAC + MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CH), azathioprine (AZA), adrenocorticotropic hormone (ACTH), non-immunosuppressive therapies (CON), steroids (STE), mizoribine (MZB), and rituximab (RIT) for patients with IMN were checked. Risk ratios (RRs) and standard mean difference (SMD) were reckoned to assess dichotomous variable quantities and continuous variable quantities, respectively. Total remission (TR) and 24-h urine total protein (24-h UTP) were compared using pairwise and NMA. Then interventions were ranked on the basis of the surface under the cumulative ranking curve (SUCRA). Results: Our study finally included 51 RCTs and 12 different immunosuppressants. Compared with the CON group, most regimens demonstrated better therapeutic effect in TR, with RR of 2.1 (95% CI) (1.5–2.9) for TAC, 1.9 (1.3–2.8) for RIT, 2.5 (1.2–5.2) for TAC + MMF, 1.9 (1.4–2.7) for CH, 1.8 (1.4–2.4) for CTX, 2.2 (1.0–4.7) for ACTH, 1.6 (1.2–2.1) for CsA, 1.6 (1.0–2.5) for LEF, and 1.6 (1.1–2.2) for MMF. In terms of 24-h UTP, TAC (SMD, −2.3 (95% CI −3.5 to −1.1)), CTX (SMD, −1.7 (95% CI −2.8 to −0.59)), RIT (SMD, −1.8 (95% CI −3.5 to −0.11)), CH (SMD, −2.4 (95% CI −4.3 to −0.49)), AZA (SMD, −−4.2 (95% CI −7.7 to −0.68)), and CsA (SMD, −1.7 (95% CI −3 to −0.49)) were significantly superior than the CON group. As for adverse effects (AEs), infections, nausea, emesia, myelosuppression, and glucose intolerance were the collective adverse events for most immunosuppressants. Conclusion: This study indicates that TAC + MMF performed the best in terms of TR, and TAC shows the best effectiveness on 24-h UTP compared with other regimens. On the contrary, there seems to be little advantage on STE alone, LEF, AZA, and MZB in treating patients with IMN compared with CON. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021287013]
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Scolari F, Alberici F, Mescia F, Delbarba E, Trujillo H, Praga M, Ponticelli C. Therapies for Membranous Nephropathy: A Tale From the Old and New Millennia. Front Immunol 2022; 13:789713. [PMID: 35300332 PMCID: PMC8921478 DOI: 10.3389/fimmu.2022.789713] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 02/07/2022] [Indexed: 11/13/2022] Open
Abstract
Primary Membranous Nephropathy (PMN) is the most frequent cause of nephrotic syndrome in adults. If untreated, PMN can lead to end-stage renal disease; moreover, affected patients are at increased risk of complications typical of nephrotic syndrome such as fluid overload, deep vein thrombosis and infection. The association of PMN with HLA-DQA1 and the identification in around 70% of cases of circulating autoantibodies, mainly directed towards the phospholipase A2 receptor, supports the autoimmune nature of the disease. In patients not achieving spontaneous remission or in the ones with deteriorating kidney function and severe nephrotic syndrome, immunosuppression is required to increase the chances of achieving remission. The aim of this review is to discuss the evidence base for the different immunosuppressive regimens used for PMN in studies published so far; the manuscript also includes a section where the authors propose, based upon current evidence, their recommendations regarding immunosuppression in the disease, while highlighting the still significant knowledge gaps and uncertainties.
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Affiliation(s)
- Francesco Scolari
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.,Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Federico Alberici
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.,Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Federica Mescia
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.,Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Elisa Delbarba
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.,Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Hernando Trujillo
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain.,Department of Nephrology, Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Manuel Praga
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain.,Department of Nephrology, Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain
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Rojas-Rivera J, Fervenza FC, Ortiz A. Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy. Drugs 2022; 82:109-132. [PMID: 34932208 PMCID: PMC8844164 DOI: 10.1007/s40265-021-01656-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/21/2021] [Indexed: 11/03/2022]
Abstract
Immunosuppressive therapy is mandatory for primary membranous nephropathy with persistent nephrotic proteinuria or anti-phospholipase A2 receptor antibodies, reduced kidney function, or another risk factor for progression. Rituximab has demonstrated efficacy for proteinuria remission compared with renin-angiotensin system blockade or cyclosporine in two well-powered randomized controlled trials. More recently, STARMEN showed that alternating glucocorticoid-cyclophosphamide is superior to sequential tacrolimus-rituximab for proteinuria remission, although it was associated with a higher risk of non-serious adverse events. However, sequential tacrolimus-rituximab involved delayed lower dose rituximab and was the worst-performing rituximab regimen among those tested in randomized clinical trials. The RI-CYCLO pilot study did not demonstrate superiority of glucocorticoid-cyclophosphamide over rituximab and found no difference in adverse events. Overall, STARMEN and RI-CYCLO confirmed the efficacy of glucocorticoid-cyclophosphamide in patients with high-risk membranous nephropathy and the role of rituximab as a valid alternative. However, none of the trials tested an optimized rituximab protocol involving a second rituximab cycle before declaring treatment failure. Calcineurin inhibitors should be considered third-line drugs and sequential use of calcineurin inhibitor rituximab did not add over rituximab-only regimens. We critically review recent randomized controlled trials, propose a research agenda, and call for multinational pragmatic trials that enroll patients at referral centers to address unmet research needs.
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Affiliation(s)
- Jorge Rojas-Rivera
- Division of Nephrology and Hypertension, Hospital Universitario Fundación Jiménez Díaz, IIS-Fundación Jiménez Díaz, and Autonomous University of Madrid, Avenida de los Reyes Católicos 2 (3rd Floor - Nephrology and Hypertension), 28040, Madrid, Spain.
| | | | - Alberto Ortiz
- Division of Nephrology and Hypertension, Hospital Universitario Fundación Jiménez Díaz, IIS-Fundación Jiménez Díaz, and Autonomous University of Madrid, Avenida de los Reyes Católicos 2 (3rd Floor - Nephrology and Hypertension), 28040, Madrid, Spain
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Chen M, Liu J, Xiong Y, Xu G. Treatment of Idiopathic Membranous Nephropathy for Moderate or Severe Proteinuria: A Systematic Review and Network Meta-Analysis. Int J Clin Pract 2022; 2022:4996239. [PMID: 35685506 PMCID: PMC9159126 DOI: 10.1155/2022/4996239] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/29/2022] [Accepted: 03/19/2022] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE Numerous studies have demonstrated that the efficacy of drugs differs in idiopathic membranous nephropathy (IMN) patients with moderate or high proteinuria. However, there is no systematic comparison confirming it. This network meta-analysis (NMA) was performed to respectively compare the efficacy of ten IMN treatments in patients with moderate and high proteinuria and compare the risk of adverse events with 10 IMN regimens. METHODS Randomized controlled trials (RCTs) and observational studies analyzing the main therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR), bone marrow suppression, and gastrointestinal symptoms. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. RESULTS Seventeen RCTs and eight observational studies involving 1778 patients were pooled for comparison of ten interventions. Steroid + tacrolimus (TAC) showed the highest probabilities of TR whether patients had severe proteinuria or not (SUCRA 89.5% and 88.9%, separately). Rituximab (RTX) was more beneficial for TR on patients with proteinuria <8 g/d (SUCRA 66.0%) and was associated with a lower risk of bone marrow suppression and gastrointestinal symptoms (SUCRA 21.7% and 21.4%, separately). TAC + RTX and steroids + cyclophosphamide induced the highest rates of bone marrow suppression (SUCRA 90.6% and 88.3%, separately) and gastrointestinal symptoms (SUCRA 86.0% and 72.1%, separately). CONCLUSIONS Steroids + TAC showed significant efficacy in patients with all degrees of proteinuria, while RTX was more effective in patients with moderate proteinuria and was safer in bone marrow suppression and gastrointestinal symptoms.
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Affiliation(s)
- Miaomiao Chen
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Grade 2018, The First Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Jiarong Liu
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yi Xiong
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Gaosi Xu
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Gong L, Xu M, Xu W, Tang W, Lu J, Jiang W, Xie F, Ding L, Qian X. Efficacy and safety of tacrolimus monotherapy versus tacrolimus-corticosteroid combination therapy for idiopathic membranous nephropathy: A meta-analysis. Medicine (Baltimore) 2021; 100:e28225. [PMID: 34941086 PMCID: PMC8702145 DOI: 10.1097/md.0000000000028225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 11/02/2021] [Accepted: 11/24/2021] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE The objective of this meta-analysis was to compare the efficacy and safety of tacrolimus (TAC) monotherapy versus TAC-corticosteroid combination therapy in idiopathic membranous nephropathy (IMN) patients. METHODS Databases including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched from inception to January 10, 2021. Eligible studies comparing TAC monotherapy and TAC-corticosteroid combination therapy in IMN patients were included. Data were analysed using Review Manager Version 5.3. RESULTS Seven studies were included in the meta-analysis. One randomized controlled trial and six cohort studies involving 372 patients were identified. Compared with TAC monotherapy, TAC-corticosteroid had a higher total remission at the sixth month (odd ratio (OR) 0.49, 95% confidence interval (CI) 0.31-0.78, P < .01). The two therapy regimens had similar complete remission rates (OR 0.79, 95% CI 0.43-1.48, P = .47) at the sixth month and similar relapse rates (OR 1.44, 95% CI 0.70-2.92, P = .32). TAC-corticosteroid combination therapy had a higher incidence of infection (OR 0.38, 95% CI 0.18-0.81, P = .01). The two therapy regimens had similar incidences of gastrointestinal symptoms (OR 0.96, 95% CI 0.34-2.70, P = .93), abnormal aminotransferase (OR 0.90, 95% CI 0.34-2.38, P = .84), and glucose intolerance (OR 0.58, 95% CI 0.32-1.07, P = .08). CONCLUSION TAC-corticosteroid combination therapy had a higher total remission rate at the sixth month but had a higher incidence of infection than TAC monotherapy in the treatment of IMN. The two therapeutic regimens had similar relapse rates.
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Affiliation(s)
- Lifeng Gong
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
| | - Min Xu
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
| | - Wei Xu
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
| | - Weigang Tang
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
| | - Jingkui Lu
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
| | - Wei Jiang
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
| | - Fengyan Xie
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
| | - Liping Ding
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
| | - Xiaoli Qian
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, China
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Lv W, Wang MR, Zhang CZ, Sun XX, Yan ZZ, Hu XM, Wang TT. Effect of Nephritis Rehabilitation Tablets combined with tacrolimus in treatment of idiopathic membranous nephropathy. World J Clin Cases 2021; 9:10464-10471. [PMID: 35004978 PMCID: PMC8686134 DOI: 10.12998/wjcc.v9.i34.10464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 08/22/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Idiopathic membranous nephropathy (IMN) has a high incidence in the middle-aged and elderly population, and poses a great threat to the physical and mental health and quality of life of patients. Nephritis Rehabilitation Tablets have many potential effects, such as clearing residual toxins, tumefying the kidney and spleen, replenishing qi, and nourishing yin, and have played an important role in the treatment of a variety of kidney diseases.
AIM To investigate the efficacy and safety of Nephritis Rehabilitation Tablets combined with tacrolimus in the treatment of IMN.
METHODS Eighty-four patients with IMN recruited from January 2017 to September 2020 were randomly divided into a study group (n = 42) and a control group (n = 42). On the basis of routine symptomatic treatment, both groups were treated with tacrolimus, and the study group was additionally treated with Nephritis Rehabilitation Tablets. Both groups were treated for 12 wk. The therapeutic effect, the levels of renal function indexes [serum creatinine (Scr), serum albumin, and 24-h urinary protein], urinary immunoglobulin (IgG4), membrane attack complex (C5b-9), and the incidence of adverse reactions were measured before and after 12 wk of treatment.
RESULTS The total effective rate in the study group was significantly higher than that of the control group. Before treatment, there was no significant difference in Scr, serum albumin, or 24 h urinary protein between the two groups. After 12 wk of treatment, the levels of Scr and 24-h urinary protein in both groups were significantly lower and serum albumin was significantly higher than those before treatment (P < 0.05), and the levels of Scr and 24-h urinary protein were significantly lower (P = 0.003 and 0.000, respectively), and the level of serum albumin was significantly higher (P = 0.00) in the study group than in the control group. Before treatment, there was no significant difference in urinary IgG4 and C5b-9 levels between the study group and the control group (P = 0.336 and 0.438, respectively). After 12 wk of treatment, the levels of urinary IgG4 and C5b-9 in the two groups were lower than those before treatment, and the levels of urinary IgG4 and C5b-9 in the study group were significantly lower than those in the control group (P = 0.000). There was no significant difference in the incidence of adverse reactions between the two groups (P = 0.710).
CONCLUSION Based on routine intervention, Nephritis Rehabilitation Tablets combined with tacrolimus in the treatment of IMN can effectively improve the renal function of patients and downregulate the expression of urinary IgG4 and C5b-9. In addition, they can improve the overall therapeutic effect while not increasing the risk of adverse reactions.
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Affiliation(s)
- Wei Lv
- Department of Nephology, China People’s Liberation Army 32298, Weifang 261000, Shandong Province, China
| | - Mei-Rong Wang
- Department of Pharmacy, China People’s Liberation Army 32298, Weifang 261000, Shandong Province, China
| | - Cheng-Zhen Zhang
- Department of Nephology, China People’s Liberation Army 32298, Weifang 261000, Shandong Province, China
| | - Xue-Xu Sun
- Department of Nephology, China People’s Liberation Army 32298, Weifang 261000, Shandong Province, China
| | - Zhen-Zhen Yan
- Department of Blood Purification, China People’s Liberation Army 32298, Weifang 261000, Shandong Province, China
| | - Xiao-Min Hu
- Department of Blood Purification, China People’s Liberation Army 32298, Weifang 261000, Shandong Province, China
| | - Tao-Tao Wang
- Department of Nephology, China People’s Liberation Army 32298, Weifang 261000, Shandong Province, China
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von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev 2021; 11:CD004293. [PMID: 34778952 PMCID: PMC8591447 DOI: 10.1002/14651858.cd004293.pub4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Without treatment, approximately 30% of patients will experience spontaneous remission and one third will have persistent proteinuria. Approximately one-third of patients progress toward end-stage kidney disease (ESKD) within 10 years. Immunosuppressive treatment aims to protect kidney function and is recommended for patients who do not show improvement of proteinuria by supportive therapy, and for patients with severe nephrotic syndrome at presentation due to the high risk of developing ESKD. The efficacy and safety of different immunosuppressive regimens are unclear. This is an update of a Cochrane review, first published in 2004 and updated in 2013. OBJECTIVES The aim was to evaluate the safety and efficacy of different immunosuppressive treatments for adult patients with PMN and nephrotic syndrome. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 1 April 2021 with support from the Cochrane Kidney and Transplant Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials (RCTs) investigating effects of immunosuppression in adults with PMN and nephrotic syndrome were included. DATA COLLECTION AND ANALYSIS Study selection, data extraction, quality assessment, and data synthesis were performed using Cochrane-recommended methods. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS Sixty-five studies (3807 patients) were included. Most studies exhibited a high risk of bias for the domains, blinding of study personnel, participants and outcome assessors, and most studies were judged unclear for randomisation sequence generation and allocation concealment. Immunosuppressive treatment versus placebo/no treatment/non-immunosuppressive treatment In moderate certainty evidence, immunosuppressive treatment probably makes little or no difference to death, probably reduces the overall risk of ESKD (16 studies, 944 participants: RR 0.59, 95% CI 0.35 to 0.99; I² = 22%), probably increases total remission (complete and partial) (6 studies, 879 participants: RR 1.44, 95% CI 1.05 to 1.97; I² = 73%) and complete remission (16 studies, 879 participants: RR 1.70, 95% CI 1.05 to 2.75; I² = 43%), and probably decreases the number with doubling of serum creatinine (SCr) (9 studies, 447 participants: RR 0.46, 95% CI 0.26 to 0.80; I² = 21%). However, immunosuppressive treatment may increase the number of patients relapsing after complete or partial remission (3 studies, 148 participants): RR 1.73, 95% CI 1.05 to 2.86; I² = 0%) and may lead to a greater number experiencing temporary or permanent discontinuation/hospitalisation due to adverse events (18 studies, 927 participants: RR 5.33, 95% CI 2.19 to 12.98; I² = 0%). Immunosuppressive treatment has uncertain effects on infection and malignancy. Oral alkylating agents with or without steroids versus placebo/no treatment/steroids Oral alkylating agents with or without steroids had uncertain effects on death but may reduce the overall risk of ESKD (9 studies, 537 participants: RR 0.42, 95% CI 0.24 to 0.74; I² = 0%; low certainty evidence). Total (9 studies, 468 participants: RR 1.37, 95% CI 1.04 to 1.82; I² = 70%) and complete remission (8 studies, 432 participants: RR 2.12, 95% CI 1.33 to 3.38; I² = 37%) may increase, but had uncertain effects on the number of patients relapsing, and decreasing the number with doubling of SCr. Alkylating agents may be associated with a higher rate of adverse events leading to discontinuation or hospitalisation (8 studies 439 participants: RR 6.82, 95% CI 2.24 to 20.71; I² = 0%). Oral alkylating agents with or without steroids had uncertain effects on infection and malignancy. Calcineurin inhibitors (CNI) with or without steroids versus placebo/no treatment/supportive therapy/steroids We are uncertain whether CNI with or without steroids increased or decreased the risk of death or ESKD, increased or decreased total or complete remission, or reduced relapse after complete or partial remission (low to very low certainty evidence). CNI also had uncertain effects on decreasing the number with a doubling of SCr, temporary or permanent discontinuation or hospitalisation due to adverse events, infection, or malignancy. Calcineurin inhibitors (CNI) with or without steroids versus alkylating agents with or without steroids We are uncertain whether CNI with or without steroids increases or decreases the risk of death or ESKD. CNI with or without steroids may make little or no difference to total remission (10 studies, 538 participants: RR 1.01, 95% CI 0.89 to 1.15; I² = 53%; moderate certainty evidence) or complete remission (10 studies, 538 participants: RR 1.15, 95% CI 0.84 to 1.56; I² = 56%; low certainty evidence). CNI with or without steroids may increase relapse after complete or partial remission. CNI with or without steroids had uncertain effects on SCr increase, adverse events, infection, and malignancy. Other immunosuppressive treatments Other interventions included azathioprine, mizoribine, adrenocorticotropic hormone, traditional Chinese medicines, and monoclonal antibodies such as rituximab. There were insufficient data to draw conclusions on these treatments. AUTHORS' CONCLUSIONS This updated review strengthened the evidence that immunosuppressive therapy is probably superior to non-immunosuppressive therapy in inducing remission and reducing the number of patients that progress to ESKD. However, these benefits need to be balanced against the side effects of immunosuppressive drugs. The number of included studies with high-quality design was relatively small and most studies did not have adequate follow-up. Clinicians should inform their patients of the lack of high-quality evidence. An alkylating agent (cyclophosphamide or chlorambucil) combined with a corticosteroid regimen had short- and long-term benefits, but this was associated with a higher rate of adverse events. CNI (tacrolimus and cyclosporin) showed equivalency with alkylating agents however, the certainty of this evidence remains low. Novel immunosuppressive treatments with the biologic rituximab or use of adrenocorticotropic hormone require further investigation and validation in large and high-quality RCTs.
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Affiliation(s)
- Thilo C von Groote
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hosptial Münster, Münster, Germany
| | | | - Eric H Au
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- Department of Renal Medicine, Westmead Hospital, Westmead, Australia
| | - Yizhi Chen
- Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Hainan Provincial Academician Team Innovation Center, Sanya, China
- Senior Department of Nephrology, the First Medical Center of Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Anna T Mathew
- Department of Nephrology, McMaster University, Hamilton, Canada
| | - Elisabeth M Hodson
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
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Rovin BH, Adler SG, Barratt J, Bridoux F, Burdge KA, Chan TM, Cook HT, Fervenza FC, Gibson KL, Glassock RJ, Jayne DR, Jha V, Liew A, Liu ZH, Mejía-Vilet JM, Nester CM, Radhakrishnan J, Rave EM, Reich HN, Ronco P, Sanders JSF, Sethi S, Suzuki Y, Tang SC, Tesar V, Vivarelli M, Wetzels JF, Floege J. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100:S1-S276. [PMID: 34556256 DOI: 10.1016/j.kint.2021.05.021] [Citation(s) in RCA: 1104] [Impact Index Per Article: 276.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022]
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Gong L, Xu M, Xu W, Tang W, Lu J, Jiang W, Xie F, Ding L, Qian X. Efficacy and safety of tacrolimus monotherapy versus cyclophosphamide-corticosteroid combination therapy for idiopathic membranous nephropathy: A meta-analysis. Medicine (Baltimore) 2021; 100:e26628. [PMID: 34260552 PMCID: PMC8284768 DOI: 10.1097/md.0000000000026628] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 06/10/2021] [Accepted: 06/23/2021] [Indexed: 01/04/2023] Open
Abstract
OBJECTIVE The objective of this meta-analysis was to compare the efficacy and safety of tacrolimus (TAC) monotherapy versus cyclophosphamide (CTX)-corticosteroid combination therapy in idiopathic membranous nephropathy (IMN) patients. METHODS Databases including the PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from inception to October 20, 2020. Eligible studies comparing TAC monotherapy and CTX-corticosteroid combination therapy in IMN patients were included. Data were analyzed using Review Manager Version 5.3. RESULTS Nine studies were included in the meta-analysis. One randomized controlled trial and eight cohort studies involving 442 patients were identified. Compared with CTX-corticosteroid combination therapy for IMN, TAC monotherapy had higher complete remission (CR) at month 6 (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.35-3.50, P < .01). The 2 therapeutic regimens had similar partial remission (OR 0.69, 95% CI 0.45-1.04, P = .08), total remission (OR 1.38, 95% CI 0.85-2.23, P = 0.19) at month 6, and similar CR (OR 1.64, 95% CI 0.84-3.19, P = .15), partial remission (OR 0.71, 95% CI 0.37-1.38, P = 0.31), and total remission (OR 1.29, 95% CI 0.55-3.01, P = .56) after 1 year. The relapse rate of the TAC group was higher than that of the CTX group, but the difference was not statistically significant (OR 1.85, 95% CI 0.75-4.53, P = .18). There was no difference between the 2 therapeutic regimens concerning glucose intolerance (OR 1.15, 95% CI 0.61-2.14, P = .67), acute renal failure (OR 1.14, 95% CI 0.39-3.33, P = .81), or tremors (OR 4.39, 95% CI 0.75-25.67, P = .10). Incidences of gastrointestinal symptoms (OR 0.29, 95% CI 0.10-0.79, P = .02), infection (OR 0.18, 95% CI 0.08-0.39, P < 0.01), leukopenia (OR 0.14, 95% CI 0.04-0.51, P < .01), and abnormal aminotransferase (OR 0.31, 95% CI 0.13-0.77, P = .01) in the TAC group were all lower than those in the CTX group. Subgroup analysis showed that there was no significant difference between the TAC group and the CTX combined with corticosteroid 0.8 to 1 mg/kg/day group concerning CR at month 6 (P > .05). There was no significant difference between the TAC group and the CTX combined with corticosteroid 0.5 mg/kg/day group concerning abnormal aminotransferase (P > .05). CONCLUSION TAC monotherapy is comparable to CTX-corticosteroid combination therapy for renal remission in IMN patients. TAC monotherapy had a higher CR in the early stage and had fewer drug-related adverse effects. The relapse rate of TAC monotherapy was higher than that of CTX-corticosteroid combination therapy, but the difference was not significant.
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Affiliation(s)
- Lifeng Gong
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
| | - Min Xu
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
| | - Wei Xu
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
| | - Weigang Tang
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
| | - Jingkui Lu
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
| | - Wei Jiang
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
| | - Fengyan Xie
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
| | - Liping Ding
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
| | - Xiaoli Qian
- Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
- Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University Changzhou, Jiangsu, China
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Ma R, Wang Y, Xu Y, Wang R, Wang X, Yu N, Li M, Zhou Y. Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy. J Diabetes Res 2021; 2021:8832114. [PMID: 34095318 PMCID: PMC8163546 DOI: 10.1155/2021/8832114] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 04/18/2021] [Accepted: 04/24/2021] [Indexed: 01/12/2023] Open
Abstract
Podocyte injury plays an important role in diabetic nephropathy (DN), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is expressed in podocytes and mediates podocyte injury induced by high glucose levels. Tacrolimus is a novel immunosuppressive agent that is reported to play an important role in podocyte protection. The purpose of this study was to investigate the potential mechanism of podocyte protection by tacrolimus in a type 2 diabetic mellitus (T2DM) rat model and in immortalized mouse podocytes (MPC5). Transmission electron microcopy was used to evaluate renal injury morphology. After treatment with FK506, we measured 24-hour urinary albumin-to-creatinine ratios and creatinine clearance rates as well as major biochemical parameters such as glucose, insulin, serum creatinine, urea nitrogen, total cholesterol, triglycerides, alanine transaminase, and aspartate aminotransferase. Nephrin and TRPC6 protein expression and podocyte apoptotic rates in vivo and in vitro were measured using immunohistochemical staining, TUNEL assays, and flow cytometry, respectively. Western blot was used to measure expression of cleaved-caspase-3 and bax/bcl-2. Exposed to high glucose (HG), DM rats exhibited disrupted biochemical conditions and impaired podocyte structure. Decreased expression of nephrin and increased expression of TRPC6, cleaved-caspase-3, and bax/bcl-2 ratios were found in podocytes, along with higher apoptotic percentage, while tacrolimus intervention counteracted the effect of HG on podocytes. Our results suggest that tacrolimus protects podocytes during the progression of type 2 diabetic nephropathy, possibly ameliorating podocyte apoptosis by downregulating the expression of TRPC6.
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Affiliation(s)
- Ruixia Ma
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Ying Wang
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Yan Xu
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Rui Wang
- Department of Intensive Care Unit, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xianghua Wang
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Ning Yu
- Department of Ultrasound, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Minghui Li
- Department of Emergency, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Yan Zhou
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
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Dai P, Xie W, Yu X, Sun J, Wang S, Kawuki J. Efficacy and cost of different treatment in patients with idiopathic membranous nephropathy: A network meta-analysis and cost-effectiveness analysis. Int Immunopharmacol 2021; 94:107376. [PMID: 33582591 DOI: 10.1016/j.intimp.2021.107376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 12/21/2020] [Accepted: 01/05/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND Idiopathic membranous nephropathy (IMN) is the most common pathological type of adult nephrotic syndrome. However, the treatments for IMN patients had not been compared from the perspectives of therapeutic effect and pharmacoeconomics. Therefore, a network meta-analysis and a cost-effectiveness analysis were conducted to find the optimum treatment for IMN patients. METHODS Randomized controlled trials (RCTs) which compared the treatments including cyclophosphamide (CTX), mycophenolate mofetil (MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CLB) and rituximab (RTX) for patients with IMN were reviewed. The complete and partial remission rates were extracted and then compared by network meta-analysis. The surface under the cumulative ranking area (SUCRA) was calculated to rank the remission rate for all treatments. Then, the cost-effectiveness analysis was performed to compared the incremental cost-effectiveness ratio (ICER) of different treatments. RESULTS A total of 75 articles with 4806 participants were included according to the inclusion and exclusion criteria. Compared with the glucocorticoids (GC) group, CTX + GC (95%RR 1.02,1.76), CsA + GC (95%RR 1.11,2.13) and TAC + GC (95%RR 1.44,2.59) were associated with a significantly higher rate of complete remission. TAC + GC were most likely to be ranked the best (SUCRA of 92.1%). From the perspective of the cost-effectiveness analysis in China, the ICER of LEF + GC to CTX + GC was $30616.336 per unit utility, and that of TAC + GC to CTX + GC was $670475.210 per unit utility. And the ICER of CTX + GC to LEF + GC in the UK was $-65680.879 per unit utility. CONCLUSIONS CTX + GC was the cheapest treatment with obvious curative effect in China, while LEF + GC was a cost-effective alternative to CTX + GC. The remission rate of TAC + GC was highest despite the high single-dose cost.
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Affiliation(s)
- Pinyuan Dai
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China.
| | - Weihua Xie
- Department of Quality Management, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
| | - Xiaojin Yu
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China.
| | - Jinfang Sun
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China.
| | - Shiyuan Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China.
| | - Joseph Kawuki
- Centre for Health Behaviours Research, JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, Hong Kong.
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Wu L, Lai J, Ling Y, Weng Y, Zhou S, Wu S, Jiang S, Ding X, Jin X, Yu K, Chen Y. A Review of the Current Practice of Diagnosis and Treatment of Idiopathic Membranous Nephropathy in China. Med Sci Monit 2021; 27:e930097. [PMID: 33550324 PMCID: PMC7876949 DOI: 10.12659/msm.930097] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Idiopathic membranous nephropathy (IMN), a common pathological type of nephrotic syndrome, is one of the main causes of kidney failure. With an increasing prevalence, IMN has received considerable attention in China. Based on recent studies, we discuss advances in the diagnosis of IMN and the understanding of its genetic background. Although the pathogenesis of IMN remains unclear, our understanding has been substantially enhanced by the discovery of new antigens such as phospholipase A2 receptor, thrombospondin type-1 domain-containing 7A, exostosin1/exostosin2, neural epidermal growth factor-like 1 protein, neural cell adhesion molecule 1, semaphorin 3B, and factor H autoantibody. However, due to ethnic, environmental, economic, and lifestyle differences and other factors, a consensus has not yet been reached regarding IMN treatment. In view of the differences between Eastern and Western populations, in-depth clinical evaluations of biomarkers for IMN diagnosis are necessary. This review details the current treatment strategies for IMN in China, including renin-angiotensin system inhibitors, corticosteroid monotherapy, cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil, adrenocorticotropic hormone, and traditional Chinese medicine, as well as biological preparations such as rituximab. In terms of management, the 2012 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines do not fully consider the characteristics of the Chinese population. Therefore, this review aims to present the current status of IMN diagnosis and treatment in Chinese patients, and includes a discussion of new approaches and remaining clinical challenges.
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Affiliation(s)
- Lianzhong Wu
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).,Department of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Jin Lai
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).,Department of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Yixin Ling
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).,Department of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Yiqin Weng
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).,Department of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Shujuan Zhou
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Siqi Wu
- Department of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Songfu Jiang
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Xiaokai Ding
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Xin Jin
- Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China (mainland)
| | - Kang Yu
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Yi Chen
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
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Guo Y, Wu X, Liu L, Zhang H, Yang L, Chen W. Efficacy of leflunomide combined with prednisone for the treatment of PLA2R-associated primary membranous nephropathy. Ren Fail 2020; 42:122-130. [PMID: 31957527 PMCID: PMC7006764 DOI: 10.1080/0886022x.2020.1713806] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Objective To evaluate the clinical efficacy and safety of leflunomide (LEF) combined with prednisone for the treatment of PLA2R-associated primary membranous nephropathy (PMN) and changes in anti-PLA2R antibody titers after treatment. Methods Sixty patients with nephrotic syndrome, biopsy-proven MN and anti-PLA2R antibody positivity were included in this study conducted from December 2017 to February 2019. The patients were randomly divided into an experimental group (n = 30) and a control group (n = 30). The patients in the experimental group were treated with LEF combined with prednisone, whereas the patients in the control group were treated with cyclophosphamide (CTX) combined with prednisone. We assessed 24-h urinary protein and serum albumin levels, kidney function markers, blood lipid levels and anti-PLA2R antibody titers before and after treatment. Adverse reactions during treatment were recorded. Results After 16 weeks of treatment, there were 2 cases of complete remission and 6 cases of partial remission in the experimental group, with a total effective rate of 26.67%. In the control group, there were 4 cases of complete remission and 8 cases of partial remission, with a total effective rate of 40% (p > .05). After 24 weeks of treatment, the total effective rates of the experimental and control groups were 66.67% and 76.67%, respectively (p > .05). There were no significant differences in 24-h urinary protein, serum albumin, kidney function marker or blood lipid levels between the two groups after treatment (p > .05). However, there were fewer adverse reactions in the experimental group than in the control group (p < .05). After treatment, serum anti-PLA2R antibody titers were clearly decreased in patients with complete remission and partial remission (p < .05), but these levels remained relatively high in patients without remission (p > .05). Conclusion LEF combined with prednisone has a certain efficacy for the treatment of PLA2R-associated PMN and provokes few adverse reactions. A large-sample randomized double-blind controlled study with a long follow-up period is needed to verify the efficacy of LEF combined with prednisone.
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Affiliation(s)
- Yaling Guo
- Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
| | - Xueping Wu
- Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
| | - Lei Liu
- Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
| | - Haifeng Zhang
- Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
| | - Lijuan Yang
- Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
| | - Weidong Chen
- Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
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Chen S, Ren S, Wang AY, Tran H, Li Z, Cheng X, Liu M, Li G, Wang L, Hong D. Comparison of the efficacy and safety of tacrolimus monotherapy and cyclophosphamide combined with glucocorticoid in the treatment of adult primary membranous nephropathy: protocol of a multicenter, randomized, controlled, open study. Trials 2020; 21:219. [PMID: 32093742 PMCID: PMC7041116 DOI: 10.1186/s13063-020-4144-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 02/05/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Idiopathic membranous nephropathy (IMN) remains the leading cause of adult nephrotic syndrome. Immunosuppressive therapy with cyclophosphamide (CTX) is often successful in reducing proteinuria, but its use is associated with severe side effects. Tacrolimus (TAC) is effective in achieving complete remission (CR) in patients with IMN. However, whether it is as effective as CTX in inducing and maintaining complete or partial remission in these patients is unknown. This trial aims to test TAC monotherapy for its non-inferiority to CTX in inducing long-term remission of proteinuria. METHODS Patients with biopsy-proven IMN with nephrotic syndrome will be randomized into a 12-month treatment period with oral TAC of 0.05-0.1 mg/kg/day for 6 months or with CTX + glucocorticoid. The efficacy of the treatment will be assessed by the remission status (based on changes in proteinuria) and relapse rate. DISCUSSION This study will test whether treatment with TAC monotherapy is superior to CTX with glucocorticoid in inducing long-term remission of proteinuria in patients with adult IMN. The role of serum anti-PLA2R antibodies in the early assessment of the response to therapy using different therapeutic regimens will also be clarified. TRIAL REGISTRATION ClinicalTrials.gov ChiCTR1800016140. Registered 12 June 2017. http://www.chictr.org.cn.
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Affiliation(s)
- Shasha Chen
- Renal Division and Institute of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Song Ren
- Renal Division and Institute of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Amanda Y Wang
- Renal and Metabolic Division, The George institute for global health, Sydney, Australia.,The Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
| | - Hieu Tran
- Department of Medicine, Ryde Hospital, Sydney, Australia
| | - Zheng Li
- Renal Department, Chengdu First People's Hospital, Chengdu, 610041, China
| | - Xiaoyun Cheng
- Renal department, Chengdu Second People's Hospital, Chengdu, 610017, China
| | - Manli Liu
- Renal department, Chengdu Third People's Hospital, Chengdu, 610031, China
| | - Guisen Li
- Renal Division and Institute of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Li Wang
- Renal Division and Institute of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Daqing Hong
- Renal Division and Institute of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu, 610072, China.
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Zheng Q, Yang H, Liu W, Sun W, Zhao Q, Zhang X, Jin H, Sun L. Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis. BMJ Open 2019; 9:e030919. [PMID: 31511292 PMCID: PMC6738938 DOI: 10.1136/bmjopen-2019-030919] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Revised: 07/05/2019] [Accepted: 08/19/2019] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome. DESIGN Systematic review and network meta-analysis. DATA SOURCES PubMed, EMbase, Cochrane Library, Web of Science, Clinical trials, SinoMed, Chinese Biomedicine, CNKI, WanFang and Chongqing VIP Information databases were comprehensively searched until February 2018. ELIGIBILITY CRITERIA Randomised clinical trials (RCTs) comparing the effects of different immunosuppressive treatments in adult patients with IMN and nephrotic syndrome were included, and all included RCTs had a study-duration of at least 6 months. DATA EXTRACTION AND SYNTHESIS Two reviewers independently screened articles, extracted data and assessed study quality. Standard pairwise meta-analysis was performed using DerSimonian-Laird random-effects model. RESULTS This study ultimately included 48 RCTs with 2736 patients and 13 immunosuppressive agents. The network meta-analysis results showed that most regimens, except for leflunomide (LEF), mizoribine (MZB) and steroids (STE), showed significantly higher probabilities of total remission (TR) when compared with non-immunosuppressive therapies (the control group),with risk ratios (RRs) of 2.71 (95% CI) 1.81 to 4.06)for tacrolimus+tripterygium wilfordii (TAC+TW), 2.16 (1.27 to 3.69) foradrenocorticotropic hormone, 2.02 (1.64 to 2.49) for TAC, 2.03 (1.13 to3.64) for azathioprine (AZA), 1.91 (1.46 to 2.50) for cyclosporine (CsA), 1.86 (1.44 to2.42) for mycophenolate mofetil (MMF), 1.85 (1.52 to 2.25) for cyclophosphamide (CTX),1.81 (1.10 to 2.98) for rituximab (RIT), 1.80 (1.38 to 2.33) for TW, 1.72 (1.35 to 2.19) for chlorambucil. As for 24 hours UTP, the direct andindirect comparisons showed that AZA (standard mean difference (SMD), -1.02(95% CI -1.90 to -0.15)), CsA (SMD, -0.70 (95% CI -1.33 to -0.08)),CTX (SMD, -1.01 (95% CI -1.44 to -0.58)), MMF (SMD, -0.98 (95% CI -1.64 to -0.32)), MZB (SMD, -0.97 (95% CI -1.90 to-0.04]), TAC (SMD, -1.16 (95% CI -1.72 to -0.60)) and TAC+TW(SMD, -2.03 (95% CI -2.94 to -1.12)) could significantly superior thancontrol, except for chlorambucil, LEF, RIT and STE. Thechanges of serum creatinine (Scr) was not significantly different between eachtreatments of immunosuppressive agents and the control, except for STE whichhas the possibility of increasing Scr (SMD, 1.00 (95% CI 0.36 to 1.64)).Comparisons among all treatments of immunosuppressive agents showed nostatistical significance in the outcome of relapse. A drenocorticotropichormone (85.1%) showed the lowest probability of relapse under the cumulativeranking curve values among all immunosuppressants. Infection,gastrointestinal symptoms, and bone marrow suppression were the common adverseevents associated with most of the immunosuppressive therapies. CONCLUSIONS This study demonstrates that TAC+TW, TAC and CTX are superior to other immunosuppressive agents in terms of TR and 24 hours UTP. Moreover, they are all at risk of infection, gastrointestinal symptoms, and myelosuppression. Furthermore, TAC could increase the risk of glucose intolerance or new-onset diabetes mellitus. Conversely, STE alone, LEF and MZB seem to have little advantage in clinical treatment of IMN. PROSPERO REGISTRATION NUMBER CRD42018094228.
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Affiliation(s)
- Qiyan Zheng
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
- Department of nephrology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
| | - Huisheng Yang
- Institute of Acupuncture and Moxibustion, China Academy of Chinese Medicine Science, Beijing, China
| | - Weijing Liu
- Department of nephrology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
| | - Weiwei Sun
- Department of nephrology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
| | - Qing Zhao
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
- Department of nephrology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
| | - Xiaoxiao Zhang
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
- Department of nephrology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
| | - Huanan Jin
- Department of nephrology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
| | - Luying Sun
- Department of nephrology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
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Zhang XJ, Ji CF, Yuan JZ, Wang L, Zhang J, Fang W, Bai DF, Hu Z. Efficacy and safety of tacrolimus-based treatment for nephrotic idiopathic membranous nephropathy in young adults: A retrospective study. Kaohsiung J Med Sci 2019; 35:633-639. [PMID: 31225949 DOI: 10.1002/kjm2.12098] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 05/16/2019] [Indexed: 11/09/2022] Open
Abstract
In China, the prevalence of idiopathic membranous nephropathy (IMN) is increasing with a younger age of onset. From January 2012 to October 2018, biopsy-proven nephrotic IMN patients aged between 15 and 40 in Taian City Central Hospital treated with tacrolimus (TAC) were retrospectively analyzed. Twelve-month follow-up data were collected. A total of 86 patients were enrolled in this study. Forty patients in the TAC group received TAC monotherapy with an initial dose of 0.05 to 0.1 mg/kg/day. Forty-six patients in the TAC + Pred group received TAC combined with oral prednisone (0.5 mg/kg/day initially). Remission rate, relapse rate, and adverse events in the two groups were assessed. Total remission (TR) rates at the end of the 3rd, 6th, and 12th month were 15%, 35%, and 77.5% (TAC group) and 28.3%, 56.5%, and 80.4% (TAC + Pred group), respectively. Compared with the TAC group, the TAC + Pred group had higher complete remission rates at the end of the 6th and 12th month, and TR rate at the 6th month was significantly higher. Twenty-four-hour urinary protein excretion, serum albumin and estimated glomerular filtration rate between the two groups were comparable during the follow-up. Decrease in proteinuria was significantly greater in the TAC + Pred group. No significant difference of relapse rate was found between the two groups. Adverse effects in the two groups were mild and controllable. Both TAC monotherapy and TAC combined with medium-dose prednisone are effective and safe for young adults with nephrotic IMN, while TAC + Pred regimen brings more benefits.
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Affiliation(s)
- Xiao-Juan Zhang
- Department of Nephrology, Qi Lu Hospital of Shandong University, Jinan, Shandong, China.,Department of Nephrology, Taian City Central Hospital, Taian, Shandong, China
| | - Cheng-Fa Ji
- Shandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co., Ltd., Linyi, Shandong, China
| | - Jiang-Zi Yuan
- Department of Nephrology, RenJi Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lei Wang
- Department of Nephrology, Taian City Central Hospital, Taian, Shandong, China
| | - Jing Zhang
- Shandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co., Ltd., Linyi, Shandong, China
| | - Wei Fang
- Department of Nephrology, RenJi Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dong-Fang Bai
- Department of Nephrology, Taian City Central Hospital, Taian, Shandong, China
| | - Zhao Hu
- Department of Nephrology, Qi Lu Hospital of Shandong University, Jinan, Shandong, China
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Yang Y, Zhao L, Xiao L, Liang Y, Wang C, Fu X, Zhu X, Yuan S, Zhu J, Zhu X, Liu Y, Li J, Luo J, Liu F, Sun L. Chlormethine Hydrochloride is Not Inferior to Tacrolimus in Treating Steroid-Resistant Nephrotic Syndrome. Kidney Blood Press Res 2018; 43:68-79. [DOI: 10.1159/000486911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 01/18/2018] [Indexed: 11/19/2022] Open
Abstract
<b><i>Background/Aims:</i></b> The present study aimed to explore the equivalence of CHL and tacrolimus (TAC), despite reports regarding the efficacy and safety of TAC in treating SRNS patients. <b><i>Methods:</i></b> A retrospective cohort study of CHL or TAC treatment was performed by collecting the medical records of SRNS patients with a pathological classification of focal segmental glomurular sclerosis (FSGS) or membranous nephropathy (MN) from December 2008 to December 2014 in a 3A grade hospital in southern China. The treatment regimen includes 6 months of induction therapy and a subsequent 6 to 30 months of maintenance therapy, which were evaluated by the scheduled follow-up and the detection of proteinuria and serum creatinine levels. The treatment outcomes were classified as complete remission, partial remission or no remission. <b><i>Results:</i></b> In a total of 146 SRNS patients, CHL treatment showed a higher proportion of complete remission (27.8% vs 14.9%) or partial remission (52.8% vs 37.8%) compared to TAC treatment (<i>P</i> < 0.10) at the stage of induction therapy. The CHL treatment of SRNS patients with FSGS showed better efficacy than treatment of the TAC group, but the difference of efficacy in the pathological type of MN between CHL and TAC group was not significant (<i>P</i> > 0.10). During maintenance therapy, the difference between the CHL and TAC groups was not significant in the SRNS patients with FSGS or MN (<i>P</i> > 0.10). In addition, the difference of adverse effects between CHL and TAC group was not significant (<i>P</i> > 0.10), although there was a slightly higher proportion of nausea and vomiting in the CHL group. <b><i>Conclusion:</i></b> The non-inferior efficacy of CHL treatment on the SRNS patients with FSGS or MN compared to TAC treatment, which highlighted CHL can be considered to be alternative treatment for SRNS patients in the clinical setting.
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