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Abstract: TH-PO994

Long-Term Outcomes of Tacrolimus Conversion to Sirolimus in Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Tawhari, Ibrahim, King Khalid University College of Medicine, Abha, Saudi Arabia
  • Park, Sookhyeon, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Ansari, Mohammed Javeed, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Leventhal, Joseph, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Gallon, Lorenzo G., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

Although calcineurin inhibitors (CNIs) such as tacrolimus have improved the outcomes of kidney transplantation, those drugs are associated with long nephrotoxicity and renal allograft dysfunction. CNI exposure minimization have gained significant interest. The long-term outcomes of late conversion of tacrolimus to sirolimus in a steroid-free immunosuppressive regimen in kidney transplant recipients have not been widely investigated by clinical trials.

Methods

Two hundred and seven kidney transplant recipients who received an induction with alemtuzumab and rapid steroid withdrawal, and a maintenance therapy with tacrolimus and mycophenolate, were randomized in 2:1 ratio to undergo conversion of tacrolimus to sirolimus or continue tacrolimus respectively at 6-12 months post-transplantation. The endpoints included the change in estimated glomerular filtration rate (eGFR), renal allograft loss, patient loss, biopsy proven graft rejection and development of de novo donor specific antibody (DSA) over 10 years follow up

Results

Of the 207 subjects, 132 subjects underwent conversion of tacrolimus to sirolimus at 6-12 months, and 75 subjects continued tacrolimus. The baseline characteristics were well-balanced between the two groups. At 10 years, the sirolimus group showed 8.18 ml/min/1.73 m2 increase in the eGFR [95% CI, 6.55 to 9.81], whereas the tacrolimus group showed a decline in the eGFR by 5.12 [95% CI, -6.71 to -3.53], the difference was statistically significant, P<0.001. There was no significant difference in terms of graft survival (hazard ratio, 1.16; 95% CI, 0.50 to 2.71), patient survival (hazard ratio, 1.26; 95% CI, 0.48 to 3.31), biopsy-proven acute rejection (hazard ratio, 1.68; 95% CI, 0.60 to 4.66], and development of de novo DSA (incidence rate; 8.33% in sirolimus group versus 10.67% in tacrolimus group, p= 0.758). The adverse effect profile was similar between the two groups.

Conclusion

This study demonstrated that late conversion of tacrolimus to sirolimus (≥ 6 months post-transplantation), is associated with a long-term improvement in the eGFR without increased risk of renal allograft rejection or graft loss.