Wound Healing Complications in Kidney Transplant Recipients Receiving Everolimus (EVR).

Abstract

Introduction: De novo use of EVR has been associated with lower incidence of CMV infection but is associated with a concentration dependent increase in wound healing adverse events (WHAE). This study specifically evaluated WHAE within a prospective randomized trial comparing EVR and mycophenolate (MPA) in kidney transplant recipients receiving tacrolimus (TAC). Methodology: In this single center prospective randomized study 288 low immunological risk kidney transplant recipients were randomized to: (G1, N=85) single 3 mg/kg dose of antithymocyte globulin, reduced exposure (TAC<5 ng/ml), EVR (4-8 ng/mL) and prednisone; (G2, N=102) basiliximab, reduced exposure TAC (6 ng/ml for 3 months then <5 ng/mL thereafter), EVR (4-8 ng/mL) and prednisone; (G3, N=101) basiliximab, TAC (6-8 ng/ml), MPA(1440 mg/day) and prednisone. All drugs were started within 24 hours of graft revascularization. None of the patients received any CMV prophylaxis. All 12 surgeons involved were not aware of the trial and therefore no specific surgical procedures were implemented. A specific case report form was developed to capture all WHAE. An ultrasound evaluation was also scheduled for all patients reaching 30 days to capture subclinical abnormalities. Results: No differences in main demographic characteristics were observed. Mean EVR concentrations at day 7 were 4.1±1.3 in G1 and 4.0±1.4 ng/ml in G2. There was no difference in the incidence of patients with at least one WHAE (28 vs. 35 vs. 25%, p=0.246) or those requiring surgical reintervention (13 vs. 13 vs. 12%, p=0,972). Total number of events was higher in G2 (35 vs. 61 vs. 42). The most frequent events observed were lymphocele (16 vs. 25 vs. 12), incisional hernia (6 vs. 11 vs. 2), urinary fistula (6 vs. 7 vs. 7) and surgical site infection (1 vs. 10 vs. 8). Ultrasound was performed in 96% of patients reaching 30 days. Among patients without previous WHAE, specific findings were observed in 13%, 11% and 4% of patients in G1, G2 and G3, respectively, mostly small fluid collections. The incidence of CMV infection was lower among patients receiving EVR (4.7 vs. 7.8 vs. 35.6, p < 0.0001), respectively. Conclusion: In this rigorous analysis involving 12 blinded surgeons the proportion of patients with any WHAE were comparable in patients receiving EVR compared to MPA, although the total number of events appears to be higher in patients receiving basiliximab induction and EVR.