Grenda Ryszard, Obrycki Łukasz
Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.
Children (Basel). 2022 Apr 11;9(4):536. doi: 10.3390/children9040536.
Therapy of immune-mediated kidney diseases has evolved during recent decades from the non-specific use of corticosteroids and antiproliferative agents (like cyclophosphamide or azathioprine), towards the use of more specific drugs with measurable pharmacokinetics, like calcineurin inhibitors (cyclosporine A and tacrolimus) and mycophenolate mofetil, to the treatment with biologic drugs targeting detailed specific receptors, like rituximab, eculizumab or abatacept. Moreover, the data coming from a molecular science revealed that several drugs, which have been previously used exclusively to modify the upregulated adaptive immune system, may also exert a local effect on the kidney microstructure and ameliorate the functional instability of podocytes, reducing the leak of protein into the urinary space. The innate immune system also became a target of new therapies, as its specific role in different kidney diseases has been de novo defined. Current therapy of several immune kidney diseases may now be personalized, based on the detailed diagnostic procedures, including molecular tests. However, in most cases there is still a space for standard therapies based on variable protocols including usage of steroids with the steroid-sparing agents. They are used as a first-line treatment, while modern biologic agents are selected as further steps in cases of lack of the efficacy or toxicity of the basic therapies. In several clinical settings, the biologic drugs are effective as the add-on therapy.
近几十年来,免疫介导性肾脏疾病的治疗已从非特异性使用皮质类固醇和抗增殖药物(如环磷酰胺或硫唑嘌呤),发展到使用具有可测量药代动力学的更特异性药物,如钙调神经磷酸酶抑制剂(环孢素A和他克莫司)和霉酚酸酯,再到使用靶向详细特定受体的生物药物,如利妥昔单抗、依库珠单抗或阿巴西普。此外,分子科学的数据表明,一些以前仅用于调节上调的适应性免疫系统的药物,也可能对肾脏微观结构产生局部作用,并改善足细胞的功能稳定性,减少蛋白质漏入尿腔。先天性免疫系统也成为新疗法的靶点,因为其在不同肾脏疾病中的具体作用已重新确定。基于详细的诊断程序,包括分子检测,目前几种免疫性肾脏疾病的治疗现在可以实现个性化。然而,在大多数情况下,基于包括使用类固醇和类固醇节约剂的可变方案的标准疗法仍有空间。它们被用作一线治疗,而现代生物制剂则在基础治疗缺乏疗效或出现毒性的情况下作为进一步的治疗选择。在几种临床情况下,生物药物作为附加疗法有效。