Glomerular macrophage index (GMI) in kidney transplant biopsies is associated with graft outcome

Abstract

Background: Macrophages in renal transplants have been shown to participate in antibody-mediated rejection and are associated with impaired renal function. We calculated the glomerular macrophage index (GMI) in a large transplant biopsy cohort, studied its quantity in different diagnostic groups, to clarify its possible impact on graft survival.Methods: GMI, defined as the mean number of macrophages in 10 glomeruli, was prospectively quantified in 1440 renal transplant biopsies over a 10-year period. The main histopathological diagnoses were grouped into eight disease entities, and GMI was compared to normal transplant biopsies as the reference group. The impact of GMI on graft survival was analyzed.Results: GMI was highest in chronic (mean 9.4) and active (9.7) antibody mediated rejections (ABMR), mixed rejections (7.6), and recurrent or de novo glomerulonephritis (7.5) and differed significantly from normal transplants (1.3) in almost all diagnostic groups. Hazard ratios for graft loss were significantly increased for all biopsies with GMI ≥1.9 compared to GMI < .5 (reference group) in an adjusted Cox regression model and increased with higher GMI levels. Biopsies with GMI ≥ 4.6 had < 60% 10-year graft-survival, compared to > 80% with GMI ≤ 1.8. Conclusion:GMI levels were predictive of graft loss independent of histological diagnoses and may guide clinicians to decide follow-up and therapy.

Changes in Numbers of Glomerular Macrophages Between Two Consecutive Biopsies and the Association With Renal Transplant Graft Survival

“…A higher GMI in those with longer time from transplantation to biopsy may be explained by an increased number of ABMR versus TCMR is seen later posttransplantation [19]. This fits with the finding of a higher GMI for ABMR versus TCMR as shown in our previous study [12].…”

“…The break points for the GMI-categories were based on relevant and clinically significant cut-offs that were presented in a previous study [12]. In the first step, Kaplan-Meier survival curves with log-rank test and univariable Cox proportional hazard regression were used to explore the association between GMI-groups and graft survival.…”

“…Besides histological evaluation, all renal transplant biopsies were scored for glomerular macrophage index (GMI) at the time of biopsy as described in detail in the study by Mölne et al [12].…”

“…Using renal transplant biopsies it was shown that the number of macrophages in the renal cortex increases/escalates during renal ischemia [5] as well as in cases of acute [9][10][11] and chronic rejection [6]. Similarly, a high number of glomerular macrophages were conclusively linked to biopsy-proven rejections and glomerular disorders [12]. Among rejections, the highest prevalence of glomerular macrophages is found in antibody-mediated rejection (ABMR) scenarios, both chronic and active [6,9,[12][13][14][15][16], but also in chronic T-cell mediated rejection (TCMR) [10][11][12].…”

“…Among rejections, the highest prevalence of glomerular macrophages is found in antibody-mediated rejection (ABMR) scenarios, both chronic and active [6,9,[12][13][14][15][16], but also in chronic T-cell mediated rejection (TCMR) [10][11][12]. The concept of a glomerular macrophage index (GMI), denoting the average number of glomerular macrophages in a biopsy, was initially explored by Magil in glomerular diseases in native kidneys [17] and later extended to transplant settings [9,12,18].…”