Histological subtyping of interstitial infiltrates and correlation with renal prognosis in anca-associated glomerulonephritis

Abstract Background and Aims Interstitial inflammatory infiltrates in ANCA associated glomerulonephritis (AAGN) are frequently observed but their correlation to clinicopathological parameters remains elusive. Method Retrospective study of 40 patients with newly diagnosed AAGN. Histological assessments using the presence of interstitial inflammatory cells were performed. Biopsy tissues were investigated by CD3, CD20, CD4, CD8, CD68+ (PG-M1), CD138 immunohistochemical staining. We assessed the presence of inflammatory cells in terms of clinical, histopathological parameters as well as the renal prognosis in a large follow-up period [47.87 months (12-216)]. Results The interstitial infiltrates were consisted of lymphocytes (CD3 T cell> CD 20 B cell) at 83%, followed by plasma cells at 43%, neutrophils at 43%, macrophages at 40% and eosinophils at 20% of the biopsies. CD8 T cells dominated the interstitial area in focal and sclerotic class, while CD8 and CD4 tended to have different expression patterns in the interstitial area (figures 1,2). Interestingly, we reported that the presence of macrophages was correlated with higher chronicity index [interstitial fibrosis (39% vs 24%, p = 0.015) and creatinine at diagnosis (4.4 vs 2.6 mg/dL, p = 0.01)], while the presence of neutrophils, lymphocytes and eosinophils was correlated with higher activity index [cellular crescents (37% vs 6%, p<0.001, 26% vs 9%, p = 0.021, 49% vs 24%, p = 0.021, respectively)]. In terms of short-term renal prognosis, only the macrophages were correlated with worst renal function at the 1st year (Cre 3.2 vs 1.8 mg/dL, p = 0.042). Regarding the long-term renal prognosis, we validated as the most reliably predictive score, amongst Berden classification and Mayo Clinic chronicity score, the ANCA renal risk score (AUC 0.694, p = 0.05) and we found that the low-risk group tended to present less severe inflammation (p = 0.029), while the presence of macrophages and eosinophils was less often present (p = 0.03 and 0.05, respectively) compared to the higher risk groups. Conclusion Identifying the differences in histopathological subtypes, in yet underestimated active tubulointerstitial lesions, could be the first step toward improving our understanding of distinct pathophysiological mechanisms and anticipating to specific treatment regimens.