Avaliação de marcadores endoteliais e hemostáticos no transplante renal e suas associações com a evolução do enxerto.

Abstract

Even after successful kidney transplantation, complications can occur leading to allograft loss or even death. Among the main associated complications, we can mention those occurring due to endothelial dysfunction and hemostasis alterations, both associated with reduced allograft survival. Thus, our objective was to evaluate endothelial (endocan, homocysteine) and hemostatic (ADAMTS13 activity and thrombin generation) markers in renal transplant recipients (RTR) and correlate them with allograft evolution. One hundred and fifteen RTRs were included, evaluated in a cross-sectional design, distributed into subgroups according to renal filtration function [creatinine levels (C1 ≤1.4 and C2 >1.4 mg/dL) and estimated glomerular filtration rate – eRFG ( R1 ≤60 and R2 >60 mL/min/1.73m2] and with time after transplantation [T1: 3 to 24; T2: 25 to 60; T3: 61 to 120 and T4: over 120 months post-transplant ] A prospective longitudinal analysis was also performed through the evaluation of medical records for a follow-up period of 5 years. Endocan was measured by the ELISA method. The evaluation of homocysteine levels was performed by enzymatic-colorimetric assay and the determination of ADAMTS13 activity by fluorescence resonance energy transfer. Thrombin generation test (TGT) was performed by the CAT (Calibrated Automated Thrombogram) method using low (LTF) and high (HTF) concentrations of tissue factor. Higher levels of endocan and homocysteine were observed among RTR with worse renal filtration function (subgroups C2 and R1), compared to RTR with better filtration function (subgroups C1 and R2). As for post-transplant time, patients with recent transplantation had higher levels of endocan (T1 subgroup) than the other RTRs, the same not being observed for homocysteine, whose values did not differ in relation to this variable. No significant differences were observed for ADAMTS13 activity values between the subgroups. Lower thrombin generation was observed among patients with worse renal filtration function (C2 subgroup), compared to RTR with preserved filtration function (C1 subgroup). According to post-transplant time, patients with longer post-transplant time (T3 and T4 subgroups) had higher levels of thrombin compared to RTR with shorter post-transplant time (T1 and T2 subgroups). Positive correlations were found for endogenous thrombin potential (ETP) and peak (in LTH and HTF) versus triglycerides and post-transplant time. Linear regression models showed that post-transplant time was an independent predictor of thrombin generation assessed by ETP. The prospective longitudinal evaluation showed that among the most frequent complications after 5 years of follow-up were urinary and respiratory infections; allograft rejection and neoplasms. When evaluating the influence of the markers measured in the cross-sectional phase of the study and their association with long term allograft rejection episodes, no significant differences were observed. Finally, all the data analyzed together allow us to conclude that endocan, homocysteine and the thrombin generation test showed to be promising tools for diagnosing and monitoring endothelial and hemostatic changes among kidney transplant patients over time. Further studies are needed to better understand the possible associations between such markers and the occurrence of long-term rejection.