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Lupus nephritis: An update on treatments and pathogenesis

机译:狼疮肾炎:治疗和发病机制的更新

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Immunosuppressive therapies for lupus nephritis (LN) have improved significantly over the past few decades, resulting in growing number of choices for treatment individualization and improved renal and patient outcomes. Corticosteroids combined with mycophenolate or cyclophosphamide induces a satisfactory response in a high proportion of Asian and Caucasian patients, but the rate of improvement varies considerably between patients. Relatively low disease flare rate was observed in Chinese patients receiving low-dose prednisolone and mycophenolate maintenance. Short-term results with calcineurin inhibitors (CNI) are encouraging, attributed both to their immunosuppressive efficacy and the action of these agents on podocyte biology leading to more rapid proteinuria suppression. Additional data, especially on the avoidance of nephrotoxicity and metabolic side effects, is required to facilitate selection of patients appropriate for this treatment. Modifications of standard regimens such as reducing corticosteroid exposure or using enteric-coated mycophenolate might help reduce treatment-related toxicities without compromising efficacy. While clinical outcomes of patients have improved with recent therapeutic advances, individual and ethnic variations in disease manifestations and treatment response, as well as the prevention of infections and long-term complications still present challenges to frontline clinicians. Recent data from histological examination and translational studies also suggest that complement activation via the alternative pathway, immune deposition on renal tubular basement membrane, and local inflammatory responses involving resident kidney cells are of pathogenic relevance in LN. The progress of clinical and translational studies has improved not only the understanding of disease mechanisms but also clinical decision making in the management of LN.
机译:在过去的几十年里,狼疮肾炎(LN)的免疫抑制疗法显着改善,导致治疗个体化和改善肾病和患者结果的选择越来越多。皮质类固醇与霉酚酸酯或环磷酰胺相结合,以高比例的亚洲和白种人患者诱导令人满意的反应,但是患者之间的改善速度变化很大。在接受低剂量泼尼松龙和霉酚酸酯维持的中国患者中观察到相对较低的疾病耀斑率。钙素素抑制剂(CNI)的短期结果是令人鼓舞的,旨在归因于其免疫抑制效果和这些药物对泛细胞生物学的作用导致更快速的蛋白尿抑制。需要额外的数据,特别是在避免肾毒性和代谢副作用时,需要促进适合这种治疗的患者。标准方案的修改,如减少皮质类固醇暴露或使用肠溶蛋白霉酚酸酯,可能有助于减少治疗相关的毒性而不会影响疗效。虽然患者的临床结果改善了最近的治疗性进展,但疾病表现和治疗反应的个体和种族变异,以及预防感染和长期并发症仍然对前线临床医生呈现挑战。来自组织学检查和翻译研究的最近数据还表明,通过替代途径,免疫沉积对肾小管基底膜的免疫沉积以及涉及常驻肾细胞的局部炎症反应的补体激活在LN中具有致病相关性。临床和翻译研究的进展不仅改善了对疾病机制的理解,而且改善了LN管理的临床决策。

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