Division of Nephrology, Department of Internal Medicine, Hannover Medical School , Hannover , Germany.
Department of Pathology, Hannover Medical School , Hannover , Germany.
Am J Physiol Renal Physiol. 2018 Sep 1;315(3):F701-F710. doi: 10.1152/ajprenal.00189.2017. Epub 2018 Apr 11.
Acute tubular injury (ATI) is common in renal allografts and is related to inferior long-term allograft function. However, it is unknown which of the morphological features of ATI can predict outcome and how they should be graded. Here, we examine features of ATI systematically in protocol biopsies and biopsies for cause to define the most predictive features. Analyses included 521 protocol biopsies taken at 6 wk, 3 mo, and 6 mo after transplantation and 141 biopsies for cause from 204 patients. Features of ATI included brush border loss, tubular epithelial lucency, flattening, pyknosis, nuclei loss, and luminal debris, each graded semiquantitatively. Additional immunohistochemical stainings were performed for markers of cell injury (neutrophil gelatinase-associated lipocalin), cell death [cleaved caspase-3, fatty acid-coenzyme A ligase 4 (FACL4)], and proliferation (K-67). Interobserver reliability was good for pyknosis, flattening, and brush border loss and poor for lucency, nuclei loss, and luminal debris. In protocol biopsies between 6 wk and 6 mo, the degree of ATI remained virtually unchanged. Biopsies for cause had generally higher injury scores. Deceased donor source, delayed graft function, ganciclovir/valganciclovir treatment, and urinary tract infection correlated with ATI. The degree of pyknosis, flattening, and brush border loss correlated best with impaired allograft function. FACL4 expression was observed in areas of ATI. Only patients with K-67 expression showed stable or improved allograft function in the longitudinal assessment. Reliable assessment of ATI is possible by semiquantitative grading of tubular epithelial cell brush border loss, flattening, and pyknosis. Examination of K-67 expression can help determine the potential for recovery from this damage.
急性肾小管损伤 (ATI) 在肾移植中很常见，与长期移植物功能低下有关。然而，目前尚不清楚 ATI 的哪些形态特征可以预测结局，以及如何对其进行分级。在这里，我们系统地检查了方案活检和因病因进行的活检中的 ATI 特征，以确定最具预测性的特征。分析包括 204 名患者的 521 份方案活检（移植后 6 周、3 个月和 6 个月时采集）和 141 份因病因进行的活检。ATI 的特征包括刷状缘丢失、管状上皮透明、扁平、固缩、核丢失和管腔碎片，每个特征均进行半定量评分。还进行了细胞损伤（中性粒细胞明胶酶相关脂质运载蛋白）、细胞死亡[裂解半胱氨酸天冬氨酸蛋白酶 3（cleaved caspase-3）、脂肪酸辅酶 A 连接酶 4（FACL4）]和增殖（K-67）的免疫组织化学染色。核丢失、管腔碎片。在 6 周至 6 个月的方案活检中，ATI 的程度几乎保持不变。因病因进行的活检通常具有更高的损伤评分。供体来源为已故、移植物延迟功能、更昔洛韦/缬更昔洛韦治疗和尿路感染与 ATI 相关。固缩、扁平、刷状缘丢失的程度与移植物功能受损相关性最好。在 ATI 区域观察到 FACL4 表达。仅在纵向评估中，具有 K-67 表达的患者显示稳定或改善的移植物功能。通过半定量评分对肾小管上皮细胞刷状缘丢失、扁平、固缩进行可靠的 ATI 评估是可能的。检查 K-67 表达有助于确定从这种损伤中恢复的潜力。
