The influence of mTOR inhibitors on the incidence of CMV infection in high-risk donor positive-recipient negative (D+/R-) kidney transplant recipients.

INTRODUCTION: Several studies and meta-analysis suggest the mTOR inhibitors are associated with reduced incidence of CMV infection after kidney transplantation, although their effects on the high-risk population have not been investigated thoroughly. OBJECTIVE: This retrospective cohort study investigates the association between immunosuppression and CMV infection in D+/R- kidney transplant recipients receiving preemptive therapy. METHODS: All patients received rabbit anti-thymocyte globulin, tacrolimus, prednisone and azathioprine (AZA), mycophenolate (MPA) or everolimus (EVR). RESULTS: Among 89 D+R-, the overall incidence of CMV infection was 76%, with no difference among the groups AZA vs MPA vs EVR (73 vs 83 vs 74%, P = 0.643). CMV infection occurred later (31 in AZA vs 31 in MPA vs 43 days in EVR group, P < 0.001) and showed a lower trend of recurrences (57% in AZA vs 79% in MPA vs 48% in EVR group, P = 0.058) in the everolimus group. There were no differences in the IgG seroconversion rate (82% in AZA vs 76% in MPA vs 72% in EVR group, P = 0.983). There were no differences in the incidence of biopsy-proven acute rejection (10% in AZA vs 8% in MPA vs 6% in EVR group, P = 0.811) and renal function at 12 months (53.6 in AZA vs 60.3 in MPA vs. 55.4 mL/min/1.73 m2 in EVR group). CONCLUSION: In this cohort of high-risk CMV D+/R- kidney transplant recipients receiving rATG induction and tacrolimus, the use of mTOR inhibitors could only show a tendency towards but not a significant difference on the incidence of CMV events, when compared to antimetabolites.

Donor-Specific Anti-Human Leukocyte Antigens Antibodies, Acute Rejection, Renal Function, and Histology in Kidney Transplant Recipients Receiving Tacrolimus and Everolimus.

BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on protocol biopsies at 12 months, and the incidence of acute rejection, estimated glomerular filtration rate (eGFR) and proteinuria at 36 months. RESULTS: At 12 months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At 36 months, there were no differences in the incidence of treatment failure (19.0 vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8 vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 ± 1.05 vs. 0.62 ± 0.75 vs. 0.71 ± 1.24). eGFR was lower in the BAS/EVR compared to that in the BAS/MPS group (53.4 ± 20.9 vs. 50.8 ± 19.5 vs. 60.7 ± 21.2 mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 ± 23 vs. 47.5 ± 22.6 vs. 53.6 ± 27.8 mL/min/1.73 m2, p = 0.207). CONCLUSION: In this cohort, the use of EVR and reduced TAC concentrations were associated with comparable efficacy, renal function, and histological parameters compared to the standard-of-care immunosuppressive regimen.

Cost-Effectiveness Analysis of Everolimus versus Mycophenolate in Kidney Transplant Recipients Receiving No Pharmacological Prophylaxis for Cytomegalovirus Infection: A Short-Term Pharmacoeconomic Evaluation (12 Months).

BACKGROUND: Modern immunosuppressive regimens, although associated with improved 1-year graft survival, are associated with adverse effects, including opportunistic infections, diabetes mellitus after transplantation, cardiovascular complications, and de novo malignancies. OBJECTIVES: To determine the short-term (12 months) cost-effectiveness of everolimus (EVR) versus mycophenolate sodium (MPS) in kidney transplant recipients receiving induction therapy, tacrolimus, prednisone, and no prophylaxis for cytomegalovirus infection. METHODS: A Markov state transition model was designed. Data from a single-center prospective trial were used along with data from the center's medical bills database. The target population comprised adults with low immunological risk submitted to first ABO-compatible transplantation with kidneys recovered from living or deceased donors. The time horizon was 12 months. The interventions included tacrolimus and prednisone plus a single 3-mg/kg dose of rabbit antithymocyte globulin (ATG) and EVR or basiliximab (BAS) and EVR or BAS and MPS. The clinical outcomes considered for this analysis were cytomegalovirus infection/disease, acute rejection, graft dysfunction, surgical complications, graft loss, and life-years gained. RESULTS: ATG/EVR was cost-saving compared with BAS/MPS on all evaluated outcomes; BAS/EVR outperformed BAS/MPS on most of the evaluated outcomes. Results were confirmed by sensitivity analysis. CONCLUSIONS: Compared with MPS, EVR is an alternative immunosuppressive agent that is able to provide resource-saving to the health care provider with effectiveness gains for the patient.