M2 macrophages predict worse long-term outcomes in human acute tubular necrosis

• Published in: Scientific reports 2020-02, Vol.10 (1), p.2122-2122, Article 2122
• Main Authors: Kim, Myung-Gyu, Lim, Kijoon, Lee, Yoo Jin, Yang, Jihyun, Oh, Se Won, Cho, Won Yong, Jo, Sang-Kyung
• Format: Article
• Language: English
• Subjects: 13/51; 692/308/53/2422; 692/4022/1585/4; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Animal models; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Biopsy; CD163 antigen; Cell Count - methods; Epidermal growth factor receptors; Female; Glomerular Filtration Rate - physiology; Humanities and Social Sciences; Humans; Immunohistochemistry; Immunohistochemistry - methods; Kidney - metabolism; Kidney - pathology; Kidney Tubular Necrosis, Acute - metabolism; Kidney Tubular Necrosis, Acute - pathology; Kidneys; Macrophages; Macrophages - metabolism; Macrophages - pathology; Male; Middle Aged; multidisciplinary; Necrosis; Receptors, Cell Surface - metabolism; Recovery of function; Retrospective Studies; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• 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.