Simultaneous vascular and antibody-mediated rejection (AMR) in pediatric patients caused poor prognosis in renal allograft
Alev Ok Atilgan1, B. Handan Ozdemir1, Esra Baskin2, F. Nurhan Ozdemir3, Mehmet Haberal4.
1Department of Pathology, Baskent University, Ankara, Turkey; 2Department of Pediatric Nephrology, Baskent University, Ankara, Turkey; 3Department of Nephrology, Baskent University, Ankara, Turkey; 4Department of General Surgery, Division of Transplantation, Baskent University, Ankara, Turkey
Introduction: The prognostic significance of simultaneous vascular rejection (VR) and AMR on graft survival is not clear enough, especially in the pediatric population. Accordingly, this study aims to determine the impact of simultaneous VR and AMR on the development of transplant glomerulopathy (TG) and interstitial fibrosis (IF) with the resulting graft survival.
Methods: Forty-five recipients younger than 18 were separated into Group 1 patients (n:25) with pure AMR and Group 2 patients (n:20) with simultaneous VR+AMR. Tubular expression of TNF-α, TGF-β, and HLA-DR was evaluated. Peritubular capillary (PTC) and interstitial leukocytes were highlighted with TNF-α, HLA-DR, and CD68. The loss of HLA-DR expression on PTCs was studied to determine the PTC destruction. Diffuse IF and TG development were analyzed in the follow-up biopsies.
Results: The response of Group 2 patients to rejection therapy was lower than Group 1 (p<0.001). PTC C4d expression was found higher in Group 2 than Group 1 (P<0.001).
Group 2 showed a higher PTC destruction, IF, and TG incidence than Group 1(P<0.01). The development of IF and TG increases with the increasing degree of glomerulitis, C4d expression, and PTC destruction (p<0.01). Tubular and interstitial TNF-α, TGF-β, and HLA-DR expressions were found higher in Group 2 compared to Group 1 (p<0.01). The degree of PTC destruction and C4d expression increased with increasing leukocyte and macrophage infiltration in PTCs and interstitium (p<0.001). The development time of IF and TG decreased with increasing intensity of PTC and interstitial infiltration, glomerulitis, PTC destruction, and C4d expression (p<0.01). Also, the development of IF and TG shortened with increasing HLA-DR, TNF-α expression in inflammatory cells and increasing TNF-α, TGF-β, HLA-DR expression in tubular cells (P<0.01). Overall, the 1-, 3- and 5-year graft survival was 96%, 92%, and 79%, respectively, for Group 1 patients, while 95%, 40%, and 10% respectively for Group 2 recipients (p<0.001).
Conclusion: The prognosis and course of antibody-mediated vascular rejection are noticeably different from pure AMR, with antibody-mediated vascular rejection having the poorest outcome through leading the early development of IF and TG via augmenting inflammatory and fibrotic pathways. Thus, developing new treatment strategies for antibody-mediated vascular rejection could salvage many kidney allografts.
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