Elderly Patients' Prognostic Disadvantage Might Be Substantiated by Distinct Tubulointerstitial Lesions in Newly Diagnosed ANCA-Associated Renal Vasculitis

Background: Although advanced age negatively predicts renal survival in antineutrophil cytoplasmic antibody (ANCA-)associated renal vasculitis (AArV), histopathological lesions substantiating this prognostic disadvantage remain elusive. Thus, we aimed to identify histopathological correlates in relation to patient’s age in newly diagnosed AArV. Methods: A total of n=45 biopsy-affirmed AArV cases were enrolled in a single-center retrospective cohort study. Receiver operating characteristics (ROC) curve analyses enabled group dichotomization. Age subgroups were compared concerning clinicolaboratory and histopathological parameters. Correlative analyses were performed regarding tubulointerstitial lesions and complement deposition in distinct renal compartments. Results: Serum C4 levels inversely correlated with patient’s age (β=-0.32, p=0.009). Maximized Youden index of ROC curve analyses for serum C4 levels (AUC 0.7, p=0.044) provided an age cut-off of 54 years enabling group dichotomization. Significantly more interstitial fibrosis (ci, p=0.0415), interstitial inflammation (i-IFTA, p=0.0062) and tubulitis (t-IFTA, p=0.0069) in areas of scarred cortex (IFTA) was observed in the elderly's subgroup. C4d-deposited interlobular arteries prevailed more often in the elderly (p=0.0031) and were associated with interstitial fibrosis (β=0.31, p=0.038) and crescent formations (β=0.44, p=0.009). Conclusion: We here show that age-dependency of renal survival in AArV might be substantiated by specific histopathological lesions characterized by interstitial fibrosis and complement deposition in the tubulointerstitial compartment of the elderly. A latent complement-driven interstitial fibrogenesis might constitute to a vulnerability of the elderly to be severely affected by an acute flare of AArV.