Comparison of Sirolimus-Based Calcineurin Inhibitor-Sparing and Calcineurin Inhibitor-Free Regimens in Cadaveric Renal Transplantation

Abstract

Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.

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

“…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.…”

A Comparative, Randomized Trial of Concentration-Controlled Sirolimus Combined With Reduced-Dose Tacrolimus or Standard-Dose Tacrolimus in Renal Allograft Recipients

“…15 Numerous single-center reports describe sirolimus/tacrolimus-based immunosuppression in organ transplant recipients. [17][18][19][20][21][22][23][24][25] Consistent with the findings of our study, a retrospective analysis by El-Sabrout et al 19 emphasized the use of sirolimus loading doses to increase rejection-free survival. In a pilot study of early tacrolimus withdrawal, Grinyo et al reported improved renal function and blood pressure in patients randomly assigned to a regimen of tacrolimus withdrawal versus those who remained on standard-dose tacrolimus and sirolimus.…”

“…16 There is an expanding body of literature on the successful clinical application of the combination of sirolimus-and tacrolimusbased immunosuppression in renal and nonerenal allograft recipients. [17][18][19][20][21][22][23][24][25] In an attempt to minimize the toxicity of tacrolimus, this study was designed to investigate the clinical safety and efficacy of a regimen of sirolimus plus reduced-dose tacrolimus (rTAC) in renal allograft recipients.…”

Protocol Transplant Biopsies

“…Our current definition of subclinical rejection requires that the serum creatinine be increased by Ͻ10% 2 wk before the protocol biopsy and that the histologic Banff score is "ai2at2" (type IA acute rejection) or greater. Numerous groups since have confirmed the occurrence of subclinical rejection as defined above, in both adults (7)(8)(9)(10)(11)(12)(13)(14) and children (15,16). Some investigators include "borderline" rejection (Banff score Ͻai2at2) in the subclinical rejection category (7,9 -11,14).…”

“…In one study (12), protocol biopsies were performed at 3 and 12 mo in patients who were randomly assigned to sirolimus and low-dose tacrolimus (calcineurin inhibitor [CNI] sparing) or sirolimus and MMF (CNIfree). Subclinical rejection was found in 6 and 15% of patients and chronic allograft nephropathy (CAN) was found in 53 and 15% of patients in the CNI-sparing and CNI-free groups, respectively.…”