Utility of Surveillance Biopsies in Kidney Transplant Recipients with Delayed Graft Function Under Current Immunosuppressive Therapy

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Abstract

Current guidelines recommend performing surveillance biopsies in kidneys of patients with delayed graft function (DGF). The guidelines were produced in an era in which the effectiveness of immunosuppressive therapy was substantially lower in terms of preventing acute rejection. The elevated incidence of DGF observed in Brazil, after deceased donor kidney transplantation, leads to an elevated necessity of performing surveillance biopsies since a higher incidence of acute rejection is observed in these patients.

Single center retrospective cohort study including deceased donor kidney transplant recipients (KTR) that received a transplant between January 2006 and July 2017 and had a graft biopsy during the DGF period. Biopsies were interpreted according to the current Banff classification. C4d deposition was evaluated in the peri-tubular capillaries and anti-donor HLA antibodies were analyzed by the Luminex® technology.

Three hundred and nine biopsies were performed in 306 KTR, predominantly males (60%), caucasians (73.5%) and unsensitized (50.3%). The mean cold ischemia time was 22.2 ± 8.5 hours and the biopsies occurred at day 13 ± 7.3 after transplantation. All patients received a calcineurin inhibitor (263 patients; 85.9%, tacrolimus), an anti-proliferative agent (295 patients; 96.4%, sodium mycophenolate) and steroids. Two hundred and eighty one patients (91.8%) received antibody induction therapy with either Basiliximab or anti T cell polyclonal antibodies. Six biopsies (1.9%) were read as normal, 126 (40.8%) presented isolated acute tubular necrosis (ATN), 83 (26.9%) presented borderline acute rejection, 83 (26.9%) presented acute rejection (AR) either cellular (79 cases) or antibody mediated (4 cases), 8 (2.6%) with cortical necrosis, 2 (0.7%) with pyelonephritis and 1 (0.3%) presented thrombotic microangiopathy. No correlation was found between recipient’s age, race, sensitization, flow cytometry cross match and graft from expanded criteria donor and acute rejection. C4d deposition in > 10% of peritubular capillaries correlated with histological acute rejection (P<0.001). In the biopsies the incidence of acute rejection varied according to the strength of the initial immunosuppressive regimen being lower in the group that received induction with anti-T cell polyclonal antibodies (12.3%), followed by induction with Basiliximab (37.0%) and by the group that did not received induction (50.0%). In unsensitized patients and in those without anti-HLA donor specific antibodies receiving induction anti-T cell polyclonal antibodies with tacrolimus, mycophenolate and prednisone a low incidence of acute rejection was found (<5%).

In conclusion surveillance biopsies in KTR undergoing DGF remain an essential tool for their clinical care. The strength of the immunosuppressive regimen alters substantially the incidence of acute rejection in this setting.

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