TORONTO—Twelve-month results of the Spare-the-Nephron study show that a regimen that spares calcineurin inhibitors (CNI) can improve renal allograft function and glomerular filtration rate (GFR).


The study compared a regimen of mycophenolate mofetil (MMF; Cellcept) plus sirolimus and a regimen of MMF plus a CNI (either tacrolimus or cyclosporine) in 298 renal transplant recipients.

Continue Reading


“The improvements we saw were significant enough to suggest that we would have fewer graft losses down the road with a Cellcept-based regimen in combination with sirolimus than with a standard CNI-containing regimen,” said lead investigator Shamkant Mulgaonkar, MD, chief of the Renal and Pancreas Transplant Division at St. Barnabas Medical Center in Livingston, N.J.


“However, I don’t think this study will change our choice of current immunosuppressant therapy drastically … but it will certainly make most physicians think of sirolimus as one option. This trial provides evidence that a CNI-free regimen can be achieved in selected patients, at least up to one year. Longer-term follow-up is required to firmly established safety and efficacy of this CNI-free regimen.”


The subjects were males and females aged 13-75 years who had received a primary renal allograft from a living or deceased donor in the previous 30-180 days. The investigators excluded subjects who had either a corticosteroid-resistant, biopsy-proven acute rejection or had been treated for acute rejection with antibody therapy in the previous 30 days.


The patients were maintained on MMF + CNI (tacrolimus [TAC] or cyclosporine [CsA]) with or without corticosteroids for 14 days before being randomized to either a continuation of MMF + CNI or to MMF + sirolimus. The medication doses were MMF 1-1.5 mg twice daily, sirolimus 2-10 mg as a loading dose and CNIs or corticosteroids at the individual centers’ standards of dosing.


Researchers randomized 148 patients to receive MMF + sirolimus and 150 to the other arm, with 119 receiving MMF/TAC and 31 receiving MMF/CsA. At baseline, the members of the two groups had similar demographic characteristics as well as donor mix, PRA levels, time post-transplant, and fraction receiving induction therapy.


The investigators, who presented study results here at the 2008 American Transplant Congress, observed a significant difference in the mean improvement in measured GFR from baseline to 12 months between the MMF/sirolimus and MMF/TAC groups (27.8% and 6.1%, respectively).


They also observed a significant difference between all three groups’ mean change in calculated GFR over one year, with a 7.4% increase for MMF/sirolimus, 1.3% increase for MMF/CNI, and a 0.1% decline for the MMF/TAC subset of CNI patients.


Additionally, the team noted a significant difference favoring sirolimus in the percentage change in calculated creatinine clearance and in the urine-protein-to-creatinine ratio. Seven percent of the patients in the three groups suffered biopsy-proven rejection, whereas similar but smaller percentages experienced graft loss or died. Both study arms had similar adverse events. Proteinuria occurred in 11% and 4% of the MMF/sirolimus and MMF/CNI arms and leucopenia occurred in 22% and 19%, respectively.