肾毒性，包括电解紊乱和急性肾损伤（AKI），限制了铂类抗肿瘤药物（例如顺铂）的临床剂量和用途。顺铂肾毒性体现为累及近端和远端肾小管的髓质 S2 和 S3 段的肾小管病变。较高剂量会扩大皮质 S1 段的损伤并加剧整体损伤。然而，基于血浆肌酐以及新型损伤生物标志物的标准诊断缺乏足够的病理生理学特异性。肾损伤检测的进一步粒度将有助于了解个性化患者处理所需的个体损伤模式的影响。在本文中，我们研究了尿神经节苷脂 GM2 激活蛋白 (GM2AP) 与 5 和 10 mg/kg 顺铂在大鼠中产生的肾小管损伤模式的关系。我们的结果表明，GM2AP 仅在近端小管皮质段受损后才出现在尿液中。 GM2AP 提供的信息与尿中性粒细胞明胶酶相关脂质运载蛋白 (NGAL) 提供的信息并不冗余，而是截然不同且互补。同样，用150mg/kg/天庆大霉素治疗会损害肾皮质并增加GM2AP尿排泄；而肾缺血不影响皮质，对 GM2AP 没有影响。由于皮质近曲小管在肾功能中的关键作用，我们认为 GM2AP 作为一种潜在的诊断生物标志物，可以根据潜在的损伤对 AKI 患者进行分层，并跟踪其演变和预后。前瞻性地，尿 GM2AP 通过成为非侵入性液体活检的一部分，可能有助于对铂类抗肿瘤肾毒性的严重程度进行分级。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.Copyright © 2024 Elsevier B.V. All rights reserved.