Department of Nephrology, Hypertension, Transplantation and Internal Medicine, Central University Hospital, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.
Int J Mol Sci. 2024 Nov 13;25(22):12174. doi: 10.3390/ijms252212174.
Minimal Change Disease (MCD) is a predominant cause of idiopathic nephrotic syndrome in the pediatric population, yet presents significant clinical challenges due to its frequent relapses and steroid resistance. Despite its relatively benign histological appearance, MCD is characterized by severe proteinuria, hypoalbuminemia, and edema, which may affect patient outcomes. Current treatment strategies primarily rely on corticosteroids, which are effective in inducing remission but are associated with high relapse rates, steroid resistance, and numerous long-term side effects, underscoring the need for more targeted and effective therapeutic approaches. This narrative review synthesizes current knowledge on the pathophysiological mechanisms underlying MCD, focusing on the following three critical areas: podocyte dysfunction, immune dysregulation, and genetic susceptibility. Podocyte dysfunction, particularly involving alterations in nephrin, plays a central role in the breakdown of the glomerular filtration barrier, leading to the characteristic proteinuria observed in MCD. Immune dysregulation, including the presence of autoantibodies against nephrin and other podocyte components, exacerbates podocyte injury and contributes to disease progression, suggesting an autoimmune component to the disease. Genetic factors, particularly mutations in the NPHS1 and NPHS2 genes, have been identified as significant contributors to disease susceptibility, influencing the variability in treatment response and overall disease severity. Understanding these mechanisms is crucial for developing targeted therapies that address the underlying causes of MCD rather than merely managing its symptoms. This review highlights the need for further research into these pathophysiological processes to pave the way for more personalized and effective treatment strategies, ultimately improving patient outcomes and reducing reliance on corticosteroids.
微小病变性肾病（MCD）是儿童特发性肾病综合征的主要病因，但由于其频繁复发和对类固醇的耐药性，仍存在显著的临床挑战。尽管其组织学表现相对良性，但 MCD 表现为严重的蛋白尿、低白蛋白血症和水肿，可能影响患者的预后。目前的治疗策略主要依赖于皮质类固醇，其在诱导缓解方面有效，但与高复发率、类固醇耐药性和许多长期副作用相关，突出了需要更有针对性和有效的治疗方法。本综述综合了目前关于 MCD 病理生理机制的知识，重点关注以下三个关键领域：足细胞功能障碍、免疫失调和遗传易感性。足细胞功能障碍，特别是涉及nephrin 的改变，在肾小球滤过屏障的破坏中起核心作用，导致 MCD 中观察到的特征性蛋白尿。免疫失调，包括针对 nephrin 和其他足细胞成分的自身抗体的存在，加剧了足细胞损伤并促进疾病进展，表明该疾病具有自身免疫成分。遗传因素，特别是 NPHS1 和 NPHS2 基因的突变，已被确定为疾病易感性的重要因素，影响治疗反应的可变性和整体疾病严重程度。了解这些机制对于开发针对 MCD 根本原因的靶向治疗至关重要，而不仅仅是管理其症状。本综述强调了需要进一步研究这些病理生理过程，为更个性化和有效的治疗策略铺平道路，最终改善患者的预后并减少对皮质类固醇的依赖。
