Sirolimus Does Not Exhibit Nephrotoxicity Compared to Cyclosporine in Renal Transplant Recipients

Abstract

Sirolimus and cyclosporine (CsA) prevent acute rejection in man when used as primary therapies in triple drug regimens. Sirolimus does not act via the calcineurin pathway and therefore is not expected to produce the same renal side-effects. This paper presents the pooled 2-year data analysis of renal function parameters from two open-label, randomized, multicenter studies. Patients (18-68 years) receiving a primary renal allograft were randomized to receive concentration-controlled sirolimus (n Ω 81) or CsA (n Ω 80), in combination with azathioprine and steroids (n Ω 83), or mycophenolate mofetil (MMF) and steroids (n Ω 78). From week 10 through year 2, calculated glomerular filtration rate (GFR) was significantly higher in sirolimus-than in CsA-treated patients (69.3 vs. 56.8 mL/min, at 2 years, p Ω0.004). Serum uric acid was significantly higher in the CsA-treated patients and magnesium was significantly lower; these parameters were more likely to be within normal limits in the sirolimus group. Mean serum potassium and phosphorus were lower in sirolimus-treated patients. In conclusion, sirolimus, when administered as primary therapy in combination with azathioprine or MMF, has a favorable safety profile compared to CsA with regards to renal function.

Sirolimus Prolongs Recovery from Delayed Graft Function After Cadaveric Renal Transplantation

“…This effect was surprising since lack of nephrotoxicity is a well-known characteristic of sirolimus (21)(22)(23)(24). Sirolimus exerts its immunosuppressive effect by inhibiting the mammalian target of rapamycin, an enzyme required for T-and B-cell proliferation and differentiation.…”

Safety and Efficacy of a Calcineurin Inhibitor Avoidance Regimen in Pediatric Renal Transplantation

“…The target levels of sirolimus that were used in this study were based on early studies of CNI-free protocols in adults (44). Earlier, uncontrolled use of sirolimus in children suggested that they may have an increased rate of metabolism of the drug, requiring more frequent dosing.…”

Factors Associated with Improvement in Deceased Donor Renal Allograft Function in the 1990s

“…Because withdrawal or avoidance of calcineurin inhibitors has been associated with an 8 to 29% increase in GFR, calcineurin-free regimens have the promise of significantly improving graft survival (11)(12)(13)(14)(15)(16). So far in early trials with early withdrawal or complete avoidance of calcineurin inhibitors, AR rates similar to those seen with calcineurin inhibitors have been achieved (13)(14)(15)(16). However, if AR rates are significantly higher with calcineurin-free regimens, then the detrimental effect of AR could negate the benefit of reduced renal toxicity with this approach to immunosuppression.…”