Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation

Gurp, Eveline Van; Bustamante, Jesús; Franco, Antônio; Rostaing, Lionel; Becker, Thomas; Rondeau, Éric; Czajkowski, Z; Rydzewski, Andrzej; Alarcón, Antonio; Bachleda, Petr; Samlík, J; Burmeister, Dirk; Pallardó, Luís; Moal, Marie-Christine; Rutkowski, Bolesław; Włodarczyk, Zbigniew

doi:10.1155/2010/731426

Cited by 17 publications

(7 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results from recent studies, however, have suggested that de novo CNI-free immunosuppression with an mTORi may incur an increased risk of acute rejection (6)(7)(8) and adverse events (9), such that complete CNI avoidance is not generally considered advisable (10). Instead, attention has focused on employing mTORi to achieve low-exposure CNI regimens (11)(12)(13)(14)(15)(16) or to facilitate CNI elimination after the initial high-risk period posttransplant (17)(18)(19)(20)(21)(22). Continuing therapy with low-exposure CNI in the presence of an mTORi, while offering effective immunosuppression, has not shown a convincing benefit in terms of renal function when initiated either at the time of transplant (6,(11)(12)(13)15) or subsequently (23,24).…”

Section: Introductionmentioning

confidence: 99%

“…Instead, attention has focused on employing mTORi to achieve low-exposure CNI regimens (11)(12)(13)(14)(15)(16) or to facilitate CNI elimination after the initial high-risk period posttransplant (17)(18)(19)(20)(21)(22). Continuing therapy with low-exposure CNI in the presence of an mTORi, while offering effective immunosuppression, has not shown a convincing benefit in terms of renal function when initiated either at the time of transplant (6,(11)(12)(13)15) or subsequently (23,24). Elimination of CNI after the period of highest immunological risk, but before development of extensive CNI-related irreversible tubulointerstitial damage (2), may be a more promising strategy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conversion From Cyclosporine to Everolimus at 4.5 Months Posttransplant: 3-Year Results From the Randomized ZEUS Study

Budde

Lehner

Sommerer

et al. 2012

American Journal of Transplantation

View full text Add to dashboard Cite

†Members listed in the Appendix.The long-term effect of conversion from calcineurin inhibitor (CNI) therapy to an mTOR inhibitor requires clarification. Following completion of the 12-month, open-label, multicenter ZEUS study, in which 300 kidney transplant recipients were randomized to continue cyclosporine (CsA) or convert to everolimus at 4.5 months posttransplant, outcomes were assessed at month 36 (n = 284; 94.7%). CNI therapy was reintroduced in 28.4% of everolimus patients by month 36. The primary efficacy endpoint, estimated glomerular filtration rate (Nankivell, ANCOVA) was significantly higher with everolimus versus the CsA group at month 24 (7.6 mL/min/1.73 m 2 , 95%CI 4.3, 11.0 mL/min/ 1.73 m 2 ; p < 0.001) and month 36 (7.5 mL/min/1.73 m 2 , 95%CI 3.6, 11.4 mL/min/1.73 m 2 ; p < 0.001). The incidence of biopsy-proven acute rejection from randomization to month 36 was 13.0% in the everolimus arm and 4.8% in the CsA arm (p = 0.015). Patient and graft survival, as well as incidences of malignancy, severe infections and hospitalization, were similar between groups. Kidney transplant patients who are converted from CsA to everolimus at month 4.5 and who remain on everolimus thereafter may achieve a significant improvement in renal function that is maintained to 3 years. There was a significantly higher rate of rejection in the everolimus arm but this did not exert a deleterious effect by 3 years posttransplant.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Conversion From Cyclosporine to Everolimus at 4.5 Months Posttransplant: 3-Year Results From the Randomized ZEUS Study

Budde

Lehner

Sommerer

et al. 2012

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…Thirty‐one RCTs evaluated sirolimus whereas six RCTs evaluated everolimus. For the primary quantitative analysis, a total of 28 RCTs were published on kidney transplantation reporting on 8916 patients (Tables 1 and 2, Table S1), [13–43] four RCTs were published on heart transplantation reporting on 1289 patients (Table S2), [44–47] one RCT [48] was published on liver transplantation reporting on 78 patients (Table S3) and one RCT [49] was published on simultaneous kidney and pancreas transplantation reporting on 123 patients (Table S4). In kidney transplantation, 14 RCTs evaluated mTOR inhibitors together with CNIs, 13 RCTs evaluated mTOR inhibitors together with antimetabolites and 1 RCT evaluated an mTOR inhibitor together with belatacept.…”

Section: Resultsmentioning

confidence: 99%

Do wound complications or lymphoceles occur more often in solid organ transplant recipients on mTOR inhibitors? A systematic review of randomized controlled trials

Pengel¹,

Liu²,

Morris³

2011

Transplant International

View full text Add to dashboard Cite

Summary mTOR inhibitors have been associated with wound complications and lymphoceles. We systematically reviewed randomized controlled trials (RCTs) to compare these outcomes for solid organ transplant recipients. Relevant medical databases were searched to identify RCTs in solid organ transplantation comparing mTOR inhibitors with an alternative therapy reporting on wound complications and/or lymphoceles. Methodological quality of RCTs was assessed. Pooled analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Thirty‐seven RCTs in kidney, heart, simultaneous pancreas‐kidney and liver transplantation were included. Pooled analyses showed a higher incidence of wound complications (OR 1.77, CI 1.31–2.37) and lymphoceles (OR 2.07, CI 1.62–2.65) for kidney transplant recipients on mTOR inhibitors together with calcineurin inhibitors (CNIs). There was also a higher incidence of wound complications (OR 3.00, CI 1.61–5.59) and lymphoceles (OR 2.13, CI 1.57–2.90) for kidney transplant recipients on mTOR inhibitors together with antimetabolites. Heart transplant patients receiving mTOR inhibitors together with CNIs also reported more wound complications (OR 1.82, CI 1.15–2.87). We found a higher incidence of wound complications and lymphoceles after kidney transplantation and a higher incidence of wound complications after heart transplantation for immunosuppressive regimens that included mTOR inhibitors from the time of transplantation.

show abstract

“…Renal function at 6 months of follow-up was comparable; however, the study was limited by short followup (27). The Edmonton protocol for islet cell transplantation consists of Tac/SRL maintenance and has been associated with nephrotoxicity (28).…”

Section: Discussionmentioning

confidence: 96%

Long-Term Kidney Allograft Function and Survival in Prednisone-Free Regimens

Chhabra

Skaro

Leventhal

et al. 2012

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryBackground and objectives The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined.Design, setting, participants, & measurements This observational study prospectively compared tacrolimus/ sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up. Patients received methylprednisonlone and anti-IL2 receptor antagonist (Basiliximab) induction and were blindly randomized to either the tacrolimus/mycophenolate mofetil (n=45) or tacrolimus/sirolimus (n=37) groups. Outcome measures included patient and renal allograft survival, incidence of acute rejection, and estimated GFR.Results The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival (91% versus 70%, P=0.02); 13 patients (35.1%) in the tacrolimus/sirolimus group and 8 patients (17.8%) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection (P=0.07). By 3 months post-transplant, estimated GFR was significantly lower in the tacrolimus/ sirolimus group compared with the tacrolimus/mycophenolate mofetil group (47.7 versus 59.6 ml/min per 1.73 m 2 , P=0.0002), and this trend persisted throughout the follow-up period. Also, the slope of decline in the tacrolimus/ sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group.Conclusions This study shows that, in a prednisone-free immunosuppressive regimen, long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/ mycophenolate mofetil group. The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival.

show abstract

Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation

Cited by 17 publications

References 21 publications

Conversion From Cyclosporine to Everolimus at 4.5 Months Posttransplant: 3-Year Results From the Randomized ZEUS Study

Conversion From Cyclosporine to Everolimus at 4.5 Months Posttransplant: 3-Year Results From the Randomized ZEUS Study

Do wound complications or lymphoceles occur more often in solid organ transplant recipients on mTOR inhibitors? A systematic review of randomized controlled trials

Long-Term Kidney Allograft Function and Survival in Prednisone-Free Regimens

Contact Info

Product

Resources

About