Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors

Abstract

Early renal dysfunction following liver transplantation is associated with increased morbidity and mortality. To evaluate the impact of delayed initiation of calcineurin inhibitor on renal function, we conducted a retrospective study comparing 118 liver transplant recipients who received rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitor with 80 liver transplant recipients who received no antibody and early initiation of calcineurin inhibitor (control group). All patients received mycophenolate mofetil and steroids. Delayed calcineurin inhibitor initiation with anti-thymocyte globulin was associated with significant improvement in renal function throughout the first year post-transplant. At 12 months post-transplant, patients treated with this regimen experienced lower serum creatinine (1.4 Ϯ 0.5 versus 1.7 Ϯ 0.5 mg/dL, P Ͻ 0.001), a higher estimated glomerular filtration rate (57.4 Ϯ 20.5 versus 43.7 Ϯ 14.4 mL/min/1.73 m 2 , P Ͻ 0.001), and less dependence on dialysis (0.8% versus 13%, P Ͻ 0.001) in comparison with no antibody and early calcineurin inhibitor initiation. Patient survival and graft survival were similar between groups; however, there was a trend of a lower incidence of early biopsy-proven acute rejection with anti-thymocyte globulin. Overall infection and cytomegalovirus infection were significantly lower in anti-thymocyte globulin-treated patients, and there was no increased incidence of hepatitis C recurrence in comparison with controls. In conclusion, delayed initiation of calcineurin inhibitor with anti-thymocyte globulin in liver transplant recipients is safe and is associated with improvements in renal function and a lower incidence of early acute rejection in comparison with no antibody and early initiation of calcineurin inhibitor. Liver Transpl 14: 66-72, 2008.

Immunosuppression in liver transplant recipients with renal impairment

“…Interestingly, the same group recently reported that a longer (10-day) Thymoglobulin-based induction therapy [29] was associated with an increased risk of infection, supporting the concept that the best risk-benefit ratio was achieved with the short induction phase. Similar results were observed by Bajjoka et al [30]. In this study, all the patients had post-operative renal dysfunction defined by the need for hemodialysis or a creatinine >1.5 mg/dl, and received MPA.…”

“…Impact of induction therapies and delayed introduction of calcineurin inhibitors on renal function after [28,[30][31][32][33]. [36] References CNI, calcineurin inhibitors; IL 2R Ab, IL2 receptors Antibodies; ATG, anti-thymocyte globulins; MMF, mycophenolate mofetil.…”

Thymoglobulin induction in liver transplant recipients with a tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: A five-year randomized prospective study

“…In the same way, similar features were observed in a large randomized study when daclizumab induction was used instead of TMG 27. The beneficial effect of TMG induction and delayed CNI introduction was shown to improve posttransplant kidney function in several studies, especially in comparison with no induction therapy and immediate CNI treatment 23, 24, 25, 28. In a retrospective study of 391 LT patients, 3‐day ATG induction therapy with the delayed use of CNIs was associated with a lower rejection rate at 1 year (14.5% versus 31.8%) and better serum creatinine levels and glomerular filtration rates at 1 year in comparison with a group of patients who received a CNI immediately after transplantation 24.…”

“…There are few studies comparing TMG and no TMG induction in LT. The majority of studies have stated that induction therapy with TMG is associated with less incidence of acute rejection, acute rejection episodes requiring corticosteroids, and corticoresistant rejection in comparison with no induction immunosuppressive regimens 13, 21–25. Only 1 randomized study from the Berlin group,26 comparing a quadruple Tac‐based induction therapy including azathioprine and TMG to a standard regimen with Tac and steroids, did not found any differences in terms of the number and severity of rejection episodes; moreover, the incidence of CMV infection was higher in the quadruple group.…”

Antibody immunosuppressive therapy in solid-organ transplant

“…Moreover, 16% of patients in the RATG group who were dialysis-dependent prior to transplant had recovered renal function. 13 According to 2007 UNOS data, 53.9% of heart transplant patients received induction therapy, with RATG being the most commonly used agent (19.2%). 7 Universal induction therapy has been shown to reduce rejection rates, but also predispose patients to a higher incidence of infectious complications and malignancies.…”