Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
Department of Pathology, Korea University Anam Hospital, Seoul, Republic of Korea.
Sci Rep. 2020 Feb 7;10(1):2122. doi: 10.1038/s41598-020-58725-w.
Although macrophages are important players in the injury/repair processes in animal models of acute kidney injury (AKI), their roles in human AKI remains uncertain owing to a paucity of human biopsy studies. We investigated the role of macrophages in 72 cases of biopsy-proven acute tubular necrosis (ATN) and six cases of healthy kidney. Macrophages were identified by CD68 and CD163 immunohistochemistry and analyzed for their effect on renal outcomes. CD163+ M2 macrophages outnumbered CD68+ cells in the healthy kidneys, suggesting that CD163+ macrophages are resident macrophages. The infiltration of both subtypes of macrophages increased significantly in ATN. The density of the CD68+ macrophages was significantly higher in advanced-stage AKI, whereas CD163+ M2 macrophages was not. Eighty percent of patients exhibited renal functional recovery during follow-up. Older age and a higher density of CD163+ macrophages predicted non-recovery, whereas the AKI stage, tubular injury score, and density of CD68+ cells did not. The density of CD163+ M2 macrophages was an independent predictor of low eGFR at 3 months in advanced-stage AKI. This is the first human study demonstrating the possible role of macrophages in the injury and repair phases of AKI.
虽然巨噬细胞在急性肾损伤（AKI）动物模型的损伤/修复过程中是重要的参与者，但由于缺乏人类活检研究，其在人类 AKI 中的作用仍不确定。我们研究了巨噬细胞在 72 例经活检证实的急性肾小管坏死（ATN）和 6 例健康肾脏中的作用。通过 CD68 和 CD163 免疫组织化学鉴定巨噬细胞，并分析其对肾脏结局的影响。健康肾脏中 CD163+ M2 巨噬细胞数量多于 CD68+细胞，表明 CD163+巨噬细胞是固有巨噬细胞。两种亚型的巨噬细胞在 ATN 中的浸润均显著增加。在晚期 AKI 中，CD68+巨噬细胞的密度显著更高，而 CD163+ M2 巨噬细胞则不然。80%的患者在随访期间表现出肾功能恢复。较老的年龄和较高密度的 CD163+巨噬细胞预示着无法恢复，而 AKI 分期、肾小管损伤评分和 CD68+细胞密度则没有。在晚期 AKI 中，CD163+ M2 巨噬细胞的密度是 3 个月时 eGFR 较低的独立预测因子。这是第一项证明巨噬细胞在 AKI 的损伤和修复阶段可能发挥作用的人类研究。
