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Thymoglobulin Induction with Tacrolimus and Everolimus Maintenance Therapy in Elderly Kidney Transplantation Results in Prolonged Lymphocyte Depletion and Do Not Favor Regulatory Profile

E. David-Neto1, G. Ramos de Freitas1, M. Fernandes1, F. Agena1, F. Brambate Carvalhinho Lemos1, F. Jota de Paula1, V. Coelho2, N. Zocoler Galante1

1Renal Transplantation Service, Hospital das Clínicas - University of São Paulo School of Medicine, Sao Paulo, Brazil, 2Laboratory of Immunology – LIM 19, Heart Institute - University of São Paulo School of Medicine, Sao Paulo, Brazil

Meeting: 2019 American Transplant Congress

Abstract number: D143

Keywords: CD4, Kidney, Lymphocytes, T cells

Session Information

Session Name: Poster Session D: Lymphocyte Biology: Signaling, Co-Stimulation, Regulation

Session Type: Poster Session

Date: Tuesday, June 4, 2019

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Despite the growing number of elderly kidney transplant (Ktx) recipientes few studies describe the effects of immunosuppression on this group. We evaluated the immunological effects of rabbit antithymocyte globulin (rATG) induction and early everolimus(EVL) conversion in elderly individuals.

*Methods: We compared three groups of KTx patients: a- Non-Elderly (n=20, 36±7y) receiving standard immunosuppression (SIS) (prednisone, tacrolimus and mycophenolate sodium) (Non-Elderly); b- Elderly receiving SIS (n=35, 65±3y) (Elderly SIS) or c- Elderly SIS with early mycophenolate to EVL conversion (EEC) (Elderly EEC) (n=16, 65±3y). At 365 days(d) elderly ISIS were 19, since 16 were converted to EVL. All with a single dose of rATG 2,0mg/Kg. Naïve, memory and regulatory peripheral blood T lymphocytes were analyzed at 0d, 30d and 365d after Ktx.

*Results: Elderly SIS presented lowering of lymphocyte absolute counts within 30 days(d) [1310(1000-16000) vs. 910 (700-11980) cells/mm3, p=0.0012], but within 365d there was no difference compared to baseline neither in Elderly SIS [1130(460-1325) cells/mm3, p=0.62] nor in those switched to Elderly EEC [1410(805-1895) cells/mm3, p>0.99] groups. Non-Elderly absolute counts did not change over time [2100(1630-2400) vs 1960(1270-2970) vs 1850(1590-2120)cells/mm3]. T central memory percentages decreased within 30d for Non-Elderly [6.2(3.77-10.8) vs 5.32(2.49-7.28)% of CD4+, p=0.036] and Elderly SIS [8.17(5.28-12.88) vs 6.74(4.36-11) % of CD4+, p=0.05], but at 365d returned to baseline. At 365d Elderly SIS presented higher percentages of T central memory cells compared to Non-Elderly [21.2(10.94-27.95) vs 8.62(4.95-13.5) % of CD4+, p=0.048], but lower percentages of TEMRA cells [7.22(5.55-11.4) vs 15.7(9.05-30.2) % of CD4+, p=0.048]. Regulatory CD39+ T cells (TREG) percentages decreased within 30d in Elderly SIS [2.01(1.23-3.51) vs 1.69(0.8-2.66) % of CD4+, p=0.0028] and Non-Elderly [1.29(0.45-1.85) vs 0.84(0.18-1.82) % of CD4+, p=0.0038] and within 365d returned to baseline in Elderly SIS and EEC groups. In Non-Elderly regulatory CD39+ T cells remained decreased at 356d [vs 0.86(0.70-1.34) % of CD4+, p=0.0156].

*Conclusions: Lymphocyte repopulation time after rATG suggests that usual rATG dose in elderly recipient should be revised in spite of the maintenance immunosuppression regimen. In this study, it was not observed a favorable effect of rATG or EVL conversion on TREG profile. Otherwise, rATG affected memory subsets. Aging favored TREG maintenance on late transplantation period and seemed to occur despite of maintenance immunosuppression.

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To cite this abstract in AMA style:

David-Neto E, Freitas GRamosde, Fernandes M, Agena F, Lemos FBrambateCarvalhinho, Paula FJotade, Coelho V, Galante NZocoler. Thymoglobulin Induction with Tacrolimus and Everolimus Maintenance Therapy in Elderly Kidney Transplantation Results in Prolonged Lymphocyte Depletion and Do Not Favor Regulatory Profile [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/thymoglobulin-induction-with-tacrolimus-and-everolimus-maintenance-therapy-in-elderly-kidney-transplantation-results-in-prolonged-lymphocyte-depletion-and-do-not-favor-regulatory-profile/. Accessed June 1, 2025.

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