Comparison of Sirolimus with Low‐Dose Tacrolimus Versus Sirolimus‐based Calcineurin Inhibitor‐Free Regimen in Live Donor Renal Transplantation

Abstract

, 132 live donor renal allotransplant recipients were included in a prospective, randomized controlled trial where they were divided into two groups. All patients received steroids and basiliximab induction therapy. For maintenance immunosuppression, tacrolimus and sirolimus were used in group A. In group B, mycophenolate mofetil (MMF) and sirolimus were utilized. Patients were followed up for a minimum of 24 months. One-year patient and graft survival rates were not significantly different between group A (96.9%, 92.3%) and group B (100%, 98.4%), respectively. However, the incidence of biopsy-proven acute rejection was less in group B but the difference was not statistically significant (13.5% vs. 18.5% in group A). Statistically significant better renal function was encountered among group B patients at two years post-transplantation as measured by serum creatinine (1.25 vs. 1.43 mg/dl; P = 0.017) and calculated glomerular filtration rate (GFR) (94.9 vs. 79.6 ml/min; P = 0.005). One year protocol biopsies showed insignificant differences relative to chronic allograft damage index (CADI) between either group (Group A: 2.41 vs. Group B: 2.69; P = 0.436). Conclusion: Similar outcome was noted among patients in whom calcineurin inhibitors were not included in their immunosuppressive regimen. The long term impact of this observation on graft survival and function needs longer follow up.

Long-term Efficacy and Safety of a Calcineurin Inhibitor-free Regimen in Live-Donor Renal Transplant Recipients

“…15 We have previously reported on the 2-yr safety and efficacy profile of SRL/steroids based regimens in combination with either low-dose Tac (group A) or MMF (group B) together with basiliximab induction therapy among live-donor renal allotransplant recipients in a prospective randomized study, and it was shown that the SRL/MMF regimen was safe regarding patient and graft survival and was associated with significant better renal function at 2 yr than the Tac/SRL regimen. 14 We hereby report on the long-term safety and efficacy profile of the same randomized patients.…”

“…Based on intention-to-treat analysis, statistically significant higher renal function obtained at 2 yr among SRL/MMF patients, 14 was maintained until the last follow-up period, a finding that comes in accordance with all short-term 12,13,20 and long-term studies 16 ; however, more recently, Larson et al, 21 in a comparison of TAC/MMF versus SRL/MMF, showed that the iothalamate clearance at 1 mo was higher in the SRL/MMF than in the TAC/MMF group (67 Ϯ 18 ml/min versus 58 Ϯ 17 ml/min); however, this difference was lost at 1 yr because of the unexpected loss of GFR in the SRL/MMF group. Differences in renal function between Larson's and other studies may be explained by the different anti-calcineurinic drugs used in the control group because it seems that CsA induces more profound renal hemodynamic changes than TAC, at least at the current target levels for clinical immunosuppression.…”

“…On studying the impact of chronic allograft damage index (CADI) obtained from protocol graft biopsies (originally 86 cases) at the end of the first post-transplant year, 14 we opted to classify whole patients of the two groups together into nearly equal two divisions: those with CADI score equal 0, 1, or 2 and those whose the score equals 4, 5, 6, or 7. Table 4 shows higher Figure 3.…”

“…11,12 However, the introduction of induction therapy with monoclonal or polyclonal antilymphocyte antibodies to the SRL/MMF and steroid combination brings an efficient acute rejection prophylaxis while improving renal function and/or reducing chronic allograft nephropathy. 13,14 However, a recent review article of an organ-by-organ review of Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients data showed a decline in the number of renal transplant patients who were discharged on regimens containing SRL down to 16% in 2004. Moreover, the use of the SRL/MMF combination has remained less than 1%.…”

“…15 We have previously reported on the safe and efficient use of SRL/MMF combination regimen together with steroids and basiliximab induction therapy in a short-term prospective randomized trial. 14 We hereby report on the safety and efficacy of the longer-term use of such a regimen in living donor renal transplant recipients.…”