Clinical Significance of Macrophage Polarization in Antibody-Mediated Rejection of Renal Allograft

Background: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. Methods: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival. Results: The glomerular M2 polarization group showed significantly higher chronic glomerulopathy scores, serum creatinine levels, and lower eGFR at the time of biopsy (P =.019 and P =.015, respectively) and 3-month postbiopsy (P =.016 and P =.032, respectively) than the M1 polarization group. The tubulointerstitial M2 polarization group had significantly lower glomerulitis, arteritis, peritubular capillaritis, and glomerulitis + peritubular capillaritis scores than the M1 polarization group, but there was no significant difference in renal function. Long-term graft survival was not associated with macrophage polarization. Conclusion: Glomerular M2 polarization in ABMR biopsy samples is associated with chronic glomerular injury and poorer graft function, but without graft survival.