Session Name: Concurrent Session: New Pathways in Allograft Rejection
Date: Tuesday, May 2, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
To determine the impact of dietary administration of the gut microbial metabolite sodium acetate (SA) on kidney rejection and survival in a fully MHC-mismatched murine model of kidney transplantation.
Methods: Life-sustaining transplants were performed: BALB/c kidney into nephrectomised C57BL/6 mice. The intervention group received 200mg/kg SA ip for 14 days post-transplantation, followed by oral 150mM SA solution (WT+SA allografts, whilst the control group received neither (WT allografts). Two experiments were performed: (1) survival study to 100 days; (2) Histological and functional assessment of groups sacrificed on days 14 and 100, to assess impact on acute and chronic allograft rejection responses respectively.
Results: WT+SA allografts had significantly increased survival compared to WT allografts (Figure 1, 16/27 vs 12/32, p<0.05). At day 14, WT+SA allografts exhibited significant reductions in serum creatinine (32.0±3.94 vs 50±19.2[micro]mol/L, p<0.05) and tubulitis scores (76.33±14.4 vs 142.7±35.3, p<0.0001) compared to WT allografts. WT+SA allografts also exhibited increased CD4+ T cell (107.1±20.6 vs 73.1±31.7 cells/HPF, p<0.05) and Foxp3+ Treg accumulation (34.3±8.2 vs 22.7±6.3 cells/HPF, p<0.01) compared to WT allografts. Similarly, day 100 WT+SA allografts also had significantly improved renal function (28.5±6.12 vs 48.8±26.8, p<0.05) and reduced proteinuria (0.40±0.27 vs 1.21±0.31mg/16hr, p<0.0001). The survival benefit conferred by SA was abolished by depletion of CD25+ Tregs using the monoclonal antibody PC61 (16/27 vs 5/17, p<0.05).
Conclusions: Dietary administration of SA was protective against the development of acute allograft rejection and chronic allograft injury. The mechanism is likely to involve increased regulation by T regulatory cells.
CITATION INFORMATION: Wu H, Kwan T, Loh Y, Chen X, Macia L, Alexander S, Chadban S. Gut Microbial Metabolite Improves Function and Prolongs Kidney Allograft Survival in Mice. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Wu H, Kwan T, Loh Y, Chen X, Macia L, Alexander S, Chadban S. Gut Microbial Metabolite Improves Function and Prolongs Kidney Allograft Survival in Mice. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/gut-microbial-metabolite-improves-function-and-prolongs-kidney-allograft-survival-in-mice/. Accessed August 3, 2021.
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