|
他克莫司较其它免疫抑制剂在儿童难治性肾病综合征中疗效比较
|
Abstract:
儿童难治性肾病综合征(Refractory nephropathy syndrome, RNS)影响着数以万计的儿童,发病率因种族和地点而异。检索文献发现近年来对于该疾病的治疗是一个巨大挑战。RNS常导致的最终结局为进行性肾功能衰竭,并且在治疗中通常存在与毒性相关的并发症、死亡率和成本问题从而变得复杂。为努力改善RNS患儿预后,同时考虑持续缓解和减少不良反应的问题,以下几种免疫抑制剂,如霉酚酸酯(MMF)、环孢菌素(CsA)、他克莫司(TAC)、环磷酰胺(CTX)和利妥昔单抗(RTX)、左旋咪唑(LMS)等已单独或结合世界各地儿童肾脏专科疾病中的广泛差异使用,因此结果各不相同。其中TAC疗效尤为突出,虽然有不少文献将TAC与各类免疫抑制剂进行两两疗效对比,但没有综合性归纳,因此,本文将对TAC与其他免疫抑制剂在治疗儿童RNS上的疗效做一个综合性论述。
Refractory nephropathy syndrome (RNS) affects tens of thousands of children, with rates varying by ethnicity and location. A search of the literature found that the treatment of the disease has been a major challenge in recent years. RNS often leads to progressive renal failure, which is often compli-cated by toxicity-related complications, mortality, and cost. In an effort to improve the prognosis of children with RNS, while considering sustained remission and reduction of adverse effects, the fol-lowing immunosuppressants, such as mycophenolate mofetil (MMF), cyclosporine (CsA), tacrolimus (TAC), cyclophosphamide (CTX) and rituximab (RTX), levamisole (LMS), etc., have been used alone or in combination with wide differences in specialist diseases of the kidney of children around the world, so the results vary. Among them, the efficacy of TAC is particularly prominent, although there are many literature comparing the efficacy of TAC with various immunosuppressants, but there is no comprehensive summary, therefore, this article will make a comprehensive discussion of the ef-ficacy of TAC and other immunosuppressants in the treatment of RNS in children.
[1] | 杨帆, 蒋小云. 儿童激素敏感、复发/依赖肾病综合征诊治循证指南(2016)解读[J]. 中华儿科杂志, 2017, 55(10): 738-742. |
[2] | Ahmed, H.M. (2019) Tacrolimus Can Induce Remission in Cyclosporine and Mycophenolate Mofetil Re-sistant Pediatric Onset Nephrotic Syndrome. Iranian Journal of Kidney Diseases, 13, 322-327. |
[3] | Sachdeva, S., Khan, S., Davalos, C., et al. (2021) Management of Steroid-Resistant Nephrotic Syndrome in Children. Cureus, 13, e19363. https://doi.org/10.7759/cureus.19363 |
[4] | Zotta, F., Vivarelli, M. and Emma, F. (2022) Update on the Treatment of Steroid-Sensitive Nephrotic Syndrome. Pediatric Nephrology, 37, 303-314. https://doi.org/10.1007/s00467-021-04983-3 |
[5] | Varghese, R. and Majumdar, A. (2022) A New Prospect for the Treatment of Nephrotic Syndrome Based on Network Pharmacology Analysis. Current Research in Physiology, 5, 36-47. https://doi.org/10.1016/j.crphys.2021.12.004 |
[6] | Vivarelli, M., Massella, L., Ruggiero, B., et al. (2017) Minimal Change Disease. Clinical Journal of the American Society of Nephrology, 12, 332-345. https://doi.org/10.2215/CJN.05000516 |
[7] | Rovin, B.H., Adler, S.G., Barratt, J., et al. (2021) Executive Summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney International, 100, 753-779. https://doi.org/10.1016/j.kint.2021.05.015 |
[8] | Mo, X., Chen, X., Wang, X., et al. (2022) Prediction of Tacrolimus Dose/Weight-Adjusted Trough Concentration in Pediatric Refractory Nephrotic Syndrome: A Machine Learning Ap-proach. Pharmacogenomics and Personalized Medicine, 15, 143-155. https://doi.org/10.2147/PGPM.S339318 |
[9] | Zhang, X., Lin, G., Tan, L., et al. (2018) Current Progress of Tacro-limus Dosing in Solid Organ Transplant Recipients: Pharmacogenetic Considerations. Biomedicine & Pharmacotherapy, 102, 107-114.
https://doi.org/10.1016/j.biopha.2018.03.054 |
[10] | 邓薇, 王利民, 黄远莲, 等. 霉酚酸酯联合他克莫司治疗激素抵抗型难治性肾病综合征分析[J]. 世界临床医学, 2019, 13(1): 64-65. |
[11] | 杨乔焕, 高岩. 免疫抑制剂在儿童难治性肾病综合征的应用进展[J]. 国际儿科学杂志, 2014, 41(3): 281-287. |
[12] | Trautmann, A., Vivarelli, M., Sam-uel, S., et al. (2020) IPNA Clinical Practice Recommendations for the Diagnosis and Management of Children with Ster-oid-Resistant Nephrotic Syndrome. Pediatric Nephrology, 35, 1529-1561.
https://doi.org/10.1007/s00467-020-04519-1 |
[13] | 耿海云, 季丽娜, 陈朝英, 等. 霉酚酸酯和环孢素A治疗儿童原发性难治性肾病综合征的临床疗效观察[J]. 中华儿科杂志, 2018, 56(9): 651-656. |
[14] | Vivarelli, M. and Em-ma, F. (2019) Levamisole for Children with Nephrotic Syndrome: New Evidence for the Use of an “Old” Drug. Kidney International, 95, 25-28. https://doi.org/10.1016/j.kint.2018.10.008 |
[15] | Muhlig, A.K., Lee, J.Y., Kemper, M.J., et al. (2019) Levamisole in Children with Idiopathic Nephrotic Syndrome: Clinical Efficacy and Pathophysiological Aspects. Journal of Clinical Medicine, 8, Article No. 860.
https://doi.org/10.3390/jcm8060860 |
[16] | Jiang, L., Dasgupta, I., Hurcombe, J.A., et al. (2015) Levamisole in Ster-oid-Sensitive Nephrotic Syndrome: Usefulness in Adult Patients and Laboratory Insights into Mechanisms of Action via Direct Action on the Kidney Podocyte. Clinical Science (London), 128, 883-893. https://doi.org/10.1042/CS20140749 |
[17] | 孙蕾, 匡新宇, 康郁林, 等. 环孢霉素A与他克莫司治疗儿童难治性肾病综合征疗效及安全性对照研究[J]. 中国实用儿科杂志, 2022, 37(8): 625-631. |
[18] | Sinha, A., Gupta, A., Kalaivani, M., et al. (2017) Mycophenolate Mofetil Is Inferior to Tacrolimus in Sustaining Remission in Children with Idiopathic Steroid-Resistant Nephrotic Syndrome. Kidney International, 92, 248-257.
https://doi.org/10.1016/j.kint.2017.01.019 |
[19] | Assadi, F., Mazaheri, M. and Sadeghi-Bodj, S. (2022) Randomized Controlled Trial to Compare Safety and Efficacy of Mycophenolate vs. Cyclosporine after Rituximab in Children with Steroid-Resistant Nephrotic Syndrome. Pharmacotherapy, 42, 690-696. https://doi.org/10.1002/phar.2721 |
[20] | Querfeld, U. and Weber, L.T. (2018) Mycophenolate Mofetil for Sustained Remission in Nephrotic Syndrome. Pediatric Nephrology, 33, 2253-2265. https://doi.org/10.1007/s00467-018-3970-y |
[21] | Ambarsari, C.G., Saraswati, M. and Laudza, G.S. (2022) Rituxi-mab, Mycophenolic Acid, and Calcineurin Inhibitors Achieve Long-Term Remission in Pediatric Focal Segmental Glo-merulosclerosis with Steroid-Resistant and Frequently Relapsing Nephrotic Syndrome: A Report of Two Cases. Case Reports in Nephrology and Dialysis, 12, 167-177.
https://doi.org/10.1159/000525776 |
[22] | Lv, J., Luo, S., Zhang, Y., et al. (2021) The Effectiveness of Cyclosporine A for Patients with Steroid-Resistant Nephrotic Syndrome: A Protocol for Systematic Review and Meta-Analysis. Medi-cine (Baltimore), 100, e28186.
https://doi.org/10.1097/MD.0000000000028186 |
[23] | Lombel, R.M., Hodson, E.M. and Gipson, D.S. (2013) Treatment of Steroid-Resistant Nephrotic Syndrome in Children: New Guidelines from KDIGO. Pediatric Nephrology, 28, 409-414. https://doi.org/10.1007/s00467-012-2304-8 |
[24] | 吴挺柏, 王婷, 阮静维. 他克莫司与环磷酰胺分别联合泼尼松治疗儿童难治性肾病综合征临床观察[J]. 中国实用医药, 2020, 15(14): 127-129. |
[25] | 张佳仪, 魏素玲, 芮淑敏, 等. 他克莫司治疗儿童激素抵抗型肾病综合征研究进展[J]. 中华实用儿科临床杂志, 2017, 32(5): 392-395. https://doi.org/10.3760/cma.j.issn.2095-428X.2017.05.020 |
[26] | Wang, L., Zhu, J., Xia, M., et al. (2022) Comparison of Rituximab, Cyclophosphamide, and Tacrolimus as First Steroid-Sparing Agents for Complicated Relaps-ing/Steroid-Dependent Nephrotic Syndrome in Children: An Evaluation of the Health-Related Quality of Life. Archives of Medical Science, 18, 275-278. https://doi.org/10.5114/aoms/145587 |
[27] | Esfahani, S.T., Afsharipour, M., Abedzadeh, A.A., et al. (2020) The Effect of Oral Cyclophosphamide in the Treatment of Children with Refractory Idio-pathic Nephrotic Syndrome. Iranian Journal of Kidney Diseases, 14, 478-481. |
[28] | Dai, P., Xie, W., Yu, X., et al. (2021) Efficacy and Cost of Different Treatment in Patients with Idiopathic Membranous Nephropathy: A Network Me-ta-Analysis and Cost-Effectiveness Analysis. International Immunopharmacology, 94, Article ID: 107376. https://doi.org/10.1016/j.intimp.2021.107376 |
[29] | Cui, K.H., Zhang, H. and Tao, Y.H. (2022) Idiopathic Membra-nous Nephropathy in Children: A Case Report. World Journal of Clinical Cases, 10, 5387-5393. https://doi.org/10.12998/wjcc.v10.i16.5387 |
[30] | Wang, R., Wang, M., Xia, Z., et al. (2021) Long-Term Renal Sur-vival and Related Risk Factors for Primary Membranous Nephropathy in Chinese Children: A Retrospective Analysis of 217 Cases. Journal of Nephrology, 34, 589-596.
https://doi.org/10.1007/s40620-020-00816-y |
[31] | Hahn, D., Hodson, E.M. and Craig, J.C. (2023) Interventions for Preventing and Treating Kidney Disease in IgA Vasculitis. The Cochrane Database of Systematic Reviews, 2, CD005128.
https://doi.org/10.1002/14651858.CD005128.pub4 |
[32] | Chang, D., Gong, M., Liu, C., et al. (2021) Efficacy and Safety of Rituximab for Childhood Refractory Nephrotic Syndrome: A Meta-Analysis of Randomized Controlled Trials. Medicina Clínica (Barc), 157, 418-426.
https://doi.org/10.1016/j.medcli.2020.07.039 |
[33] | Colucci, M., Carsetti, R., Cascioli, S., et al. (2016) B Cell Re-constitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome. Journal of the American Society of Nephrology, 27, 1811-1822.
https://doi.org/10.1681/ASN.2015050523 |
[34] | Bashford-Rogers, R., Bergamaschi, L., McKinney, E.F., et al. (2019) Analysis of the B Cell Receptor Repertoire in Six Immune-Mediated Diseases. Nature, 574, 122-126. https://doi.org/10.1038/s41586-019-1595-3 |
[35] | Roussel, A., Delbet, J.D., Micheland, L., et al. (2019) Quality of Life in Children with Severe Forms of Idiopathic Nephrotic Syndrome in Stable Remission—A Cross-Sectional Study. Acta Paediatrica, 108, 2267-2273.
https://doi.org/10.1111/apa.14912 |
[36] | Wang, L., Hua, R., Zhu, Y., et al. (2021) Single Dose of Rituximab in Children with Steroid-Dependent/Frequently Relapsing Nephrotic Syndrome, Clinical Efficacy and Evaluation of Health-Related Quality of Life. Iranian Journal of Kidney Diseases, 1, 109-115. |
[37] | Ravani, P., Lugani, F., Pisani, I., et al. (2020) Rituximab for Very Low Dose Steroid-Dependent Nephrotic Syndrome in Children: A Randomized Con-trolled Study. Pediatric Nephrology, 35, 1437-1444.
https://doi.org/10.1007/s00467-020-04540-4 |
[38] | Chan, E.Y., Webb, H., Yu, E., et al. (2020) Both the Rituximab Dose and Maintenance Immunosuppression in Steroid-Dependent/Frequently-Relapsing Nephrotic Syndrome Have Im-portant Effects on Outcomes. Kidney International, 97, 393-401. https://doi.org/10.1016/j.kint.2019.09.033 |
[39] | You, L., Ye, P., Xiao, G., et al. (2021) Rituximab for the Treatment of Idiopathic Membranous Nephropathy with Nephrotic Syndrome: A Systematic Review and Meta-Analysis. Turkish Journal of Medical Sciences, 51, 2870-2880.
https://doi.org/10.3906/sag-2104-177 |
[40] | Angioi, A., Lepori, N., Lopez, A.C., et al. (2018) Treatment of Primary Membranous Nephropathy: Where Are We Now? Journal of Nephrology, 31, 489-502. https://doi.org/10.1007/s40620-017-0427-5 |
[41] | Cybulsky, A.V., Walsh, M., Knoll, G., et al. (2014) Canadian So-ciety of Nephrology Commentary on the 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis: Management of Glomerulonephritis in Adults. American Journal of Kidney Diseases, 63, 363-377. https://doi.org/10.1053/j.ajkd.2013.12.001 |
[42] | Otukesh, H., Hoseini, R., Rahimzadeh, N., et al. (2013) Rituximab in the Treatment of Nephrotic Syndrome: A Systematic Review. Iranian Journal of Kidney Diseases, 7, 249-256. |
[43] | Zion, E., Borovitz, Y., Alfandary, H., et al. (2022) A Clinical Response-Adjusted Steroid Treatment Pro-tocol for Children with Newly Diagnosed Idiopathic Nephrotic Syndrome. American Journal of Kidney Diseases, 80, 473-482.
https://doi.org/10.1053/j.ajkd.2022.04.007 |
[44] | Dartevel, A., Chaigne, B., Moachon, L., et al. (2019) Levami-sole-Induced Vasculopathy: A Systematic Review. Seminars in Arthritis and Rheumatism, 48, 921-926. https://doi.org/10.1016/j.semarthrit.2018.07.010 |
[45] | Krischock, L., Pannila, P. and Kennedy, S.E. (2021) Levami-sole and ANCA Positivity in Childhood Nephrotic Syndrome. Pediatric Nephrology, 36, 1795-1802. https://doi.org/10.1007/s00467-020-04915-7 |
[46] | Gruppen, M.P., Bouts, A.H., Jansen-van, D.W.M., et al. (2018) A Randomized Clinical Trial Indicates That Levamisole Increases the Time to Relapse in Children with Steroid-Sensitive Idiopathic Nephrotic Syndrome. Kidney International, 93, 510-518. https://doi.org/10.1016/j.kint.2017.08.011 |
[47] | Sinha, A., Puraswani, M., Kalaivani, M., et al. (2019) Efficacy and Safety of Mycophenolate Mofetil versus Levamisole in Frequently Relapsing Nephrotic Syndrome: An Open-Label Randomized Controlled Trial. Kidney International, 95, 210-218. https://doi.org/10.1016/j.kint.2018.08.039 |
[48] | Larkins, N.G., Liu, I.D., Willis, N.S., et al. (2020) Non-Corticosteroid Immunosuppressive Medications for Steroid- Sensitive Nephrotic Syndrome in Children. The Cochrane Database of Systematic Reviews, 4, CD002290.
https://doi.org/10.1002/14651858.CD002290.pub5 |
[49] | Lombel, R.M., Gipson, D.S. and Hodson, E.M. (2013) Treatment of Steroid-Sensitive Nephrotic Syndrome: New Guidelines from KDIGO. Pediatric Nephrology, 28, 415-426. https://doi.org/10.1007/s00467-012-2310-x |
[50] | Basu, B., Babu, B.G. and Mahapatra, T.K. (2017) Long-Term Ef-ficacy and Safety of Common Steroid-Sparing Agents in Idiopathic Nephrotic Children. Clinical and Experimental Nephrology, 21, 143-151.
https://doi.org/10.1007/s10157-016-1266-8 |