Related Experiment Video
Updated: Dec 29, 2025
Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry
Published on: October 18, 2016
M2 macrophages predict worse long-term outcomes in human acute tubular necrosis
Myung-Gyu Kim1, Kijoon Lim1, Yoo Jin Lee2
1Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
Abstract:
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.
Insights
In human acute kidney injury (AKI), specific macrophage subtypes play a role in kidney repair. Higher levels of CD163+ M2 macrophages predict poor renal recovery and lower estimated glomerular filtration rate (eGFR).
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Macrophages are crucial in animal models of acute kidney injury (AKI) but their role in human AKI is unclear.
- Limited human biopsy studies hinder understanding of macrophage involvement in human AKI pathogenesis and recovery.
Purpose of the Study:
- To investigate the role and subtypes of macrophages in human acute tubular necrosis (ATN), a common form of AKI.
- To analyze the association between macrophage density and renal functional recovery in patients with ATN.
Main Methods:
- Examined kidney biopsies from 72 patients with biopsy-proven ATN and 6 healthy controls.
- Identified macrophage subtypes using CD68 and CD163 immunohistochemistry.
- Correlated macrophage densities with clinical outcomes, including renal function recovery and estimated glomerular filtration rate (eGFR).
Main Results:
- Both CD68+ and CD163+ macrophage subtypes infiltrated significantly in ATN kidneys compared to healthy controls.
- CD68+ macrophage density correlated with advanced AKI stage, while CD163+ macrophage density did not.
- Higher CD163+ macrophage density predicted poorer renal recovery and lower eGFR at 3 months, independent of AKI stage.
Conclusions:
- This study provides the first human evidence suggesting macrophages contribute to both injury and repair phases in human AKI.
- CD163+ M2 macrophages may serve as a predictive biomarker for non-recovery and long-term renal dysfunction after ATN.
- Further research is warranted to elucidate the precise mechanisms of macrophage action in human AKI.
