Durable Improvement in Renal Function With Sirolimus in Kidney Transplant Patients

Jim Kling

May 14, 2010

May 14, 2010 (San Diego, California) —The Concept study has shown that delayed introduction of sirolimus, in combination with mycophenolate mofetil (MMF), has a beneficial effect on renal function at 1 year. Now, after 48 months of follow-up, the data show that these effects are durable. The work was presented here at the American Transplant Congress 2010.

Despite the improvement in renal function demonstrated 1 year after kidney transplantation, adverse effects have limited its use, the Concept researchers noted. The 155 patients enrolled in the 48-month follow-up phase were split into 2 groups: one given sirolimus plus MMF and the other given a cyclosporine A (CsA)-based regimen. Researchers evaluated safety and renal function, estimated with the simplified Modification of Diet in Renal Disease formula at each visit.

Patients receiving sirolimus plus MMF had a significantly higher estimated glomerular filtration rate than patients receiving CsA (58.71 mL/min per 1.73 m2 vs 51.41 mL/min per 1.73m2; P = .002).

Between months 12 and 48, there were 4 deaths (2 in each group), 3 graft losses (2 in the sirolimus group, 1 in the CsA group), and 6 cases of biopsy-proven acute rejection (4 in the sirolimus group, 2 in the CsA group).

At 48 months, there was no difference between the 2 groups in lipid profile or proteinuria. Three cancers occurred in the sirolimus group, and 12 occurred in patients taking MMF and a calcineurin inhibitor at the time of cancer diagnosis.

The results bolster the 1-year findings, announced lead investigator Yvon Lebranchu, MD, PhD, professor of nephrology and clinical immunology at the University of Tours in France.

"The calcineurin-inhibitor-free regimen maintains better renal function at 4 years. [That] is not very long term, but it is not short term," Dr. Lebranchu told Medscape Transplantation.

The study "demonstrated that you can convert someone from a calcineurin inhibitor to a noncalcineurin inhibitor regimen and you'll have an improvement of renal function with a long duration of follow-up," Todd Pesavento, MD, medical director of kidney and pancreas transplantation at the Ohio State University Medical Center in Columbus, who comoderated the session, told Medscape Transplantation.

"Most of the studies have been 1 year exclusively. I think it's reassuring that over a long period of time you still maintain good renal function," Dr. Pesavento noted.

The study received support from Roche. Dr. Lebranchu and Dr. Pesavento have disclosed no relevant financial relationships.

American Transplant Congress (ATC) 2010: Abstract 376. Presented May 4, 2010.