Effects of Three Immunosuppressive Regimens On Renal Function in Kidney Transplant Recipients.

Abstract

Introduction: Renal function is associated with long-term renal allograft survival. Everolimus (EVR) have been combined with reduced exposure of calcineurin inhibitors (CNi) and therefore may determine superior renal function compared to those patients receiving standard exposure CNi and mycophenolate (MPA). Methods: 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 h of revascularization. No patient received CMV prophylaxis. This analysis evaluated renal function at 6 months using estimated glomerular filtration rate (eGFR) by MDRD. A last observation carried forward was used for patients who died with functioning graft. An eGFR=0 was attributed to patients with graft loss. Results: The mean age was 44.6±13.3 years, 66% male, 52% Caucasian, 69% recipients of deceased donors. There was no difference in the incidence of delayed graft function (DGF, 48 vs. 53 vs. 45%, p=0.3) or in the incidence of biopsy proven acute rejection (8 vs. 20 vs. 14%, p=0.08). At month 6 there were no differences in mean creatinine (1.5±1.0 vs. 1.4±0.6 vs. 1.4±1.0 mg/dl, p=0.54), mean eGFR (64±24 vs. 58±23 vs. 66±29ml/min, p=0.06) and mean urinary protein concentration (0.5±1.0 vs. 0.4±0.7 vs. 0.3±0.9 g/l, p=0.5), respectively. Among patients with DGF, lower eGFR was observed in G2 (67±28 vs. 48±24 vs. 63±35 ml/min, p=0.03). There were no differences in eGFR among patients with biopsy proven acute rejection (56±26 vs. 46±22 vs. 71±45 ml/min, p= 0.11) and CMV infection (78±22 vs. 55±29 vs. 68±30 ml/min, p=0.38), respectively. The proportion of patients with eGFR<50ml/min was higher in G2 (24% vs. 38% vs. 24%, p=0.033). Protocol biopsies performed at month 12 in 86/181 patients (G1=31, G2=32 G3=23) showed chronic allograft nephropathy in 7(22%), 5(15%) and 4(17%) patients (p= 0.76). Conclusion: This preliminary analysis suggests that EVR with antithymocyte globulin induction is associated with similar renal function compared to patients receiving MPA. DISCLOSURES:Tedesco, H.: Grant/Research Support, Novartis.