Lee Han Sean, Wu Henry H L, Ponnusamy Arvind, Alderson Helen, Chinnadurai Rajkumar
Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK.
Renal Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, The University of Sydney, Sydney, NSW 2065, Australia.
Antibodies (Basel). 2025 Mar 12;14(1):25. doi: 10.3390/antib14010025.
Diabetic nephropathy (DN) is one of the key causes of end-stage kidney disease worldwide, especially in developed countries. The classic pathogenic development of DN is characterized by microalbuminuria which would progress to nephrotic-range proteinuria and loss of kidney function. The degree of albuminuria is considered an independent risk factor for all-cause mortality in patients with DN. It is now well established that albuminuria stems from disruptions in podocyte structure and function. Podocytes play a major role in the glomerular filtration barrier. The nephrin protein has been identified as a core component of the slit diaphragm in podocytes, and as such, the downregulation of nephrin expression has been described well in various proteinuric glomerulopathies, including DN. Previous studies have shown that the presence of urinary nephrin potentially signifies an early marker of podocyte injury in DN. More recently, there have been increasing bodies of evidence which suggest that circulating autoantibodies targeting nephrin contributes to the pathogenesis of podocytopathies. However, the functional significance of these circulating autoantibodies in patients with DN is not well understood. In this review, we aim to evaluate the significance of nephrin dysregulation in the pathogenesis of DN based on the current available literature and provide an overview on the application of circulating anti-nephrin autoantibodies in relation to its diagnostic as well as prognostic role in podocytopathies, including DN.
糖尿病肾病（DN）是全球范围内终末期肾病的主要病因之一，在发达国家尤为如此。DN的典型致病发展特征为微量白蛋白尿，进而会发展为肾病范围蛋白尿和肾功能丧失。蛋白尿程度被认为是DN患者全因死亡率的独立危险因素。现已明确，蛋白尿源于足细胞结构和功能的破坏。足细胞在肾小球滤过屏障中起主要作用。nephrin蛋白已被确定为足细胞裂孔隔膜的核心成分，因此，在包括DN在内的各种蛋白尿性肾小球病中，nephrin表达下调已有充分描述。既往研究表明，尿中nephrin的存在可能预示着DN中足细胞损伤的早期标志物。最近，越来越多的证据表明，靶向nephrin的循环自身抗体参与了足细胞病的发病机制。然而，这些循环自身抗体在DN患者中的功能意义尚不清楚。在本综述中，我们旨在根据现有文献评估nephrin失调在DN发病机制中的意义，并概述循环抗nephrin自身抗体在包括DN在内的足细胞病诊断及预后方面的应用。
