Calcineurin Free Protocol Is Associated With Increase in FOXP3 Expression in the Peripheral Blood of Recipients of Extended Criteria Donor Kidneys.

Abstract

Background: The significance of the factor forkhead box (FOXP3) expression in the peripheral blood of renal transplant recipients (RTx) of extended (ECD) or standard (SCD) criteria donor kidneys is yet to be determined. Aim: To investigate the clinical significance of FOXP3 level in relation to the type of kidney donor, immunosuppressive protocol (ISS) and graft function in stable ECD RTx. Methods: Prospective, open label study with 36 stable RTx randomized according to the type of donor to receive tacrolimus (TAC; n= 19) or everolimus (EVL; n=17) based protocols combined to mycophenolate sodium, prednisone and induction therapy with basiliximab. Using qRT-PCR we measured FOXP3 expression in the peripheral blood of patients (pts) at the 3rd month after Tx. Results: Greater expression of FOXP3 was observed in recipients of ECD when compared to SCD (ECD=1.98 ± 2.8 vs SCD= 0.63 ± 0.71; p=0.02). EVL based immunosuppression (EVL= 1.49 ± 2.1 vs TAC= 0.51 ± 0.57; p=0.03) and absence of DGF post-Tx (DGF- = 1.94 ± 2.5 vs DGF+ = 0.54 ± 0.6; p=0.014) were also associated with high levels of FOXP3 expression. Cold ischemia time, acute rejection episodes and serum creatinine (sCr) at 3rd month were not associated with changes in FOXP3 expression. Multivariate logistic regression analysis showed that ECD (p= 0.025) absence of DGF (0.015) were independently associated with high levels of FOXP3. Correlation between sCr and FOXP3 was inverse in TAC treated pts and positive in those taking EVL (r= 0.74, P = 0.007). FOXP3 expression was low in kidneys with mild or no chronic lesions (IFTA score < 2) regardless the ISS. Patients treated with EVL presenting IFTA score ≥ 2 had increased expression of FOXP3 (p=NS vs TAC). Conclusions: Results suggest that recipients of ECD kidneys without having undergone DGF, treated with EVL presented an increased expression of FOXP3 in their peripheral blood. The higher FOXP3 levels associated with more chronic histological lesions may represent an anti-inflammatory response elicited by ongoing chronic allograft damage. DISCLOSURES:Abbud-Filho, M.: Grant/Research Support, Novartis. Dias, C.: Grant/Research Support, Novartis. Caldas, H.: Grant/Research Support, Novartis. Nunes, R.: Grant/Research Support, Novartis. Mazeti, C.: Grant/Research Support, Novartis. Fernandes-Charpiot, I.: Grant/Research Support, Novartis. Baptista, M.: Grant/Research Support, Novartis. Abbud-Filho, M.: Grant/Research Support, Novartis.