Del Vecchio Lucia, Allinovi Marco, Rocco Paolo, Brando Bruno
Department of Nephrology and Dialysis, Sant'Anna Hospital, ASST Lariana, 22042 Como, Italy.
Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital, 50134 Florence, Italy.
J Clin Med. 2021 Dec 13;10(24):5847. doi: 10.3390/jcm10245847.
Rituximab is a chimeric anti-CD20 monoclonal antibody. It acts mainly through complement-dependent cytotoxicity on B cells expressing the CD20 marker. In this review, we analyse the efficacy and possible pitfalls of rituximab to treat nephrotic syndromes by taking into account pharmacological considerations and CD19 marker testing utility. Despite the fact that the drug has been in use for years, efficacy and treatment schedules in adults with nephrotic syndrome are still a matter of debate. Clinical trials have proven the efficacy and safety of rituximab in idiopathic membranous nephropathy. Data from observational studies also showed the efficacy of rituximab in minimal change disease and focal segmental glomerulosclerosis. Rituximab use is now widely recommended by new Kidney Disease Improved Outcome (KDIGO) guidelines in membranous nephropathy and in frequent-relapsing, steroid-dependent minimal change disease or focal segmental glomerulosclerosis. However, rituximab response has a large interindividual variability. One reason could be that rituximab is lost in the urine at a higher extent in patients with nonselective nephrotic proteinuria, exposing patients to different rituximab plasma levels. Moreover, the association between CD19+ levels and clinical response or relapses is not always present, making the use of this marker in clinical practice complex. High resolution flow cytometry has increased the capability of detecting residual CD19+ B cells. Moreover, it can identify specific B-cell subsets (including IgG-switched memory B cells), which can repopulate at different rates. Its wider use could become a useful tool for better understanding reasons of rituximab failure or avoiding unnecessary retreatments.
利妥昔单抗是一种嵌合抗CD20单克隆抗体。它主要通过对表达CD20标志物的B细胞产生补体依赖性细胞毒性作用。在本综述中，我们通过考虑药理学因素和CD19标志物检测的实用性，分析了利妥昔单抗治疗肾病综合征的疗效及可能存在的问题。尽管该药物已使用多年，但成人肾病综合征的疗效和治疗方案仍存在争议。临床试验已证明利妥昔单抗在特发性膜性肾病中的疗效和安全性。观察性研究的数据也显示了利妥昔单抗在微小病变肾病和局灶节段性肾小球硬化症中的疗效。目前，新的改善全球肾脏病预后组织（KDIGO）指南广泛推荐在膜性肾病以及频繁复发、依赖类固醇的微小病变肾病或局灶节段性肾小球硬化症中使用利妥昔单抗。然而，利妥昔单抗的反应存在较大的个体差异。一个原因可能是在非选择性肾病性蛋白尿患者中，利妥昔单抗在尿液中的丢失程度更高，导致患者体内利妥昔单抗的血浆水平不同。此外，CD19+水平与临床反应或复发之间的关联并不总是存在，这使得该标志物在临床实践中的应用变得复杂。高分辨率流式细胞术提高了检测残留CD19+ B细胞的能力。此外，它还可以识别特定的B细胞亚群（包括IgG转换记忆B细胞），这些亚群可以以不同的速率重新增殖。更广泛地使用高分辨率流式细胞术可能成为一个有用的工具，有助于更好地理解利妥昔单抗治疗失败的原因或避免不必要的再次治疗。
