Excellent Kidney-Transplant Outcomes Seen After Early Steroid Withdrawal

Marlene Busko

January 18, 2007

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.

"This experience confirms the findings of a number of other single centers that have reported low rates of rejection and generally excellent outcomes after early steroid withdrawal in kidney-transplant recipients," Don Hricik, MD, from the University Hospitals of Cleveland and Case Western Reserve University, in Ohio, who was not involved in this study, told Medscape.

Are Steroid-Sparing Protocols Superior?

The researchers explain that in recent years, as immunosuppressive regimens in solid-organ transplant have become more effective in improving 1-year graft survival, the primary concern in selecting an immunosuppressive protocol has shifted from preventing acute rejection to minimizing long-term morbidity and mortality. They add that corticosteroids are associated with risk for diabetes, hyperlipidemia, hypertension, bone disease, and obesity. When transplant recipients were asked, in a recent survey, which drug they would choose to discontinue if there were no associated risk, 65% chose to discontinue steroids.

In the past 5 years, several centers have adopted steroid-free maintenance immunosuppressive protocols and have reported encouraging results &#8212; acute rejection rates ranging from 10% to 25%.
In the present study, the team examined the clinical outcomes of all patients who received first kidney transplants at their center from April 2002 to October 2004 under a new steroid-free maintenance immunosuppressive protocol. They compared this with outcomes of all patients at their center who received first kidney transplants from January 2000 to June 2003 under a steroid-based protocol.

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.


Excellent Outcomes, Relatively Low-Risk Patients

The 1-year patient and graft survival were excellent in both groups, and the acute rejection was only 4.9% in the steroid-free group.

1-Year Post&#8211;Kidney-Transplant Outcomes
Outcome
Steroid-Free Maintenance (%)
Steroid-Based Maintenance (%)
P
Patient survival
93.1
95.2
NS
Death-censored graft survival
98.1
95.2
NS
Biopsy-proven acute rejection
4.9
9.4
< .01

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.

In the first year posttransplant, the mean weight gain in patients in the steroid-free group was lower than in the comparator group (8.1% vs 13.5%; P < .05), but both groups had similar blood lipid levels and blood pressure control. It is "somewhat disappointing" that the authors were not able to demonstrate any other discernible metabolic benefits of the steroid-free regimen, said Dr. Hricik.

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.

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