Steroid free induction and maintainence protocols in kidney transplant

Excellent Kidney-Transplant Outcomes Seen After Early Steroid Withdrawal

Marlene Busko

January 18, 2007 — Primary kidney-transplant recipients maintained on sirolimus (Rapamune, Wyeth) and cyclosporine (Neoral, Novartis) immunosuppression after a 5-day induction with antithymocyte globulin (Thymoglobulin, Genzyme Transplant) and prednisone (Solu-Medrol, Pfizer) had excellent 1-year graft and patient survival, similar to that of a comparator group receiving steroids. In this single-center study, the steroid-free group also had a lower incidence of biopsy-proven acute rejection than the comparator group (4.9% vs 9.4%; P < .01).

"We conclude that excellent graft survival with a significantly lower incidence of acute rejection can be achieved using a steroid-free maintenance immunosuppressive protocol consisting of Neoral and sirolimus," the group, led by Amer Rajab, MD, from Ohio State University in Columbus, write.

The article is published in the December 2006 issue of Clinical Transplantation.
The immunosuppressive regimens of the 2 groups were:

• Steroid-free-maintenance group (n=301) — Induction therapy with Thymoglobulin and prednisone over 5 and 4 days, respectively, followed by maintenance therapy with sirolimus and Neoral.
• Steroid-based-maintenance group (n = 502) — Induction therapy with basiliximab (Simulect, Novartis), followed by maintenance therapy with prednisone, mycophenolate mofetil (MMF, Cellcept, Roche), and Neoral.

The low rate of acute rejection is a "remarkable" contrast with studies from the early 1990s that suggested that early steroid withdrawal was associated with high rates of acute rejection, said Dr. Hricik. He added that the only logical explanation is that the combination of sirolimus and Neoral is more potent than earlier immunosuppressants, which is discussed in a recent review article about steroid sparing that he coauthored (Clin J Am Soc Nephrol. 2006;1:1080-1089). In the current study, therapy with sirolimus and Neoral produced no significant adverse effects.

He noted that 1 weakness of this study is that there were more cadaveric donors and fewer living donors in the comparator group than in the steroid-free group, possibly accounting for the different rejection rates. Also, it is also not clear whether the results can be extrapolated to high-risk patients such as non-primary-kidney-transplant recipients or African Americans.

Clin Transplant. 2006;20:537-546.