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Randomized Controlled Trial
. 2011 Sep;22(9):1758-68.
doi: 10.1681/ASN.2011010006. Epub 2011 Aug 1.

Randomized trial of immunosuppressive regimens in renal transplantation

Giselle Guerra  1 , Gaetano Ciancio, Jeffrey J Gaynor, Alberto Zarak, Randolph Brown, Lois Hanson, Junichiro Sageshima, David Roth, Linda Chen, Warren Kupin, Lissett Tueros, Phillip Ruiz, Alan S Livingstone, George W Burke 3rd
Affiliations
Randomized Controlled Trial

Randomized trial of immunosuppressive regimens in renal transplantation

Giselle Guerra et al. J Am Soc Nephrol. 2011 Sep.

Abstract

The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown. We conducted a randomized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus, tacrolimus/mycophenolate mofetil (MMF), and cyclosporine/sirolimus. All patients received daclizumab induction and maintenance corticosteroids. Median follow-up was 8 yr post-transplant. Acute rejection (AR) occurred significantly less often among those treated with tacrolimus/MMF (12%) than among those treated with tacrolimus/sirolimus (30%) or cyclosporine/sirolimus (28%). Mean estimated GFR was consistently higher in the tacrolimus/MMF arm, especially after controlling for donor age in a multivariable model during the first 36 mo (P ≤ 0.008). The rate of dying with a functioning graft was significantly higher among those treated with tacrolimus/sirolimus (26%) than among those treated with tacrolimus/MMF (12%) or cyclosporine/sirolimus (4%). We did not observe significant differences in actuarial graft survival at 8 yr post-transplant between the groups. Patient noncompliance seemed responsible for 45% (13/29) of observed graft failures, with 11 of these occurring after 36 mo. Significantly more viral infections, protocol violations, and need for antilipid therapy occurred among patients receiving sirolimus, but we did not observe differences between the groups with regard to infections requiring hospitalization or new-onset diabetes. Taken together, these results suggest that maintenance therapy with tacrolimus/MMF is more favorable than either tacrolimus/sirolimus or cyclosporine/sirolimus.

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Figures

Figure 1.
Figure 1.
Freedom-from-AR by treatment arm (intent-to-treat).
Figure 2.
Figure 2.
Freedom-from-AR Comparison of TAC/MMF versus TAC/SRL and CSA/SRL arms combined, among higher-risk patients (those having ≥2 of non-Caucasian race/ethnicity, recipient age <50 yr, and donor age ≥50 yr; intent-to-treat). Note that separate Kaplan-Meier curves for the TAC/SRL (n = 23, 13 events) and CSA/SRL (n = 24, 12 events) arms would overlay on top of the curve shown for the two arms combined.
Figure 3.
Figure 3.
Freedom-from-graft failure-with-compliance by treatment arm (intent-to-treat).
Figure 4.
Figure 4.
Graft survival by treatment arm (intent-to-treat).
Figure 5.
Figure 5.
Freedom-from-protocol violation by treatment arm (intent-to-treat).
See this image and copyright information in PMC

References

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