Switching to Sirolimus Doesn’t Slow Chronic Changes after Transplantation

For kidney transplant patients going through rapid steroid withdrawal, switching from tacrolimus to sirolimus doesn’t reduce the rate of long-term changes on subsequent renal biopsy specimens, according to a report in Transplantation.

The randomized controlled trial included 122 kidney transplant recipients undergoing rapid steroid withdrawal. At 1 month, the patients were assigned to switch from tacrolimus to sirolimus or to remain taking tacrolimus. Protocol biopsy specimens were obtained at 1 month, 1 year, and 2 years for assessment of long-term changes, including interstitial fibrosis and tubular atrophy (IFTA) and the sum of Banff chronic scores (Total Score). The influence of previous rejection episodes on the long-term scores was assessed as well.

One-year biopsy specimens were obtained from 90 percent of patients in both groups. The two groups had similar and significant increases in long-term changes—i.e., proportion of biopsy specimens with IFTA scores of 2 or greater and Total Scores greater than 2. At 1 year, patients who had previous episodes of rejection and who continued to receive tacrolimus had higher IFTA scores and were more likely to have Total Scores greater than 2. Among those without previous rejection, both the IFTA and the Total Score showed significant progression from 1 to 2 years.

Chronic calcineurin inhibitor nephrotoxicity contributes to the development of IFTA after kidney transplantation. In a previous report, the authors found no difference in 1-year kidney function among patients who were converted from tacrolimus to sirolimus 1 month after transplantation.

The new analysis showed no reduction in the progression of IFTA and other long-term changes through 2 years in kidney recipients switched to sirolimus, compared with those continuing with tacrolimus. This was so even in patients with no previous episodes of rejection. Further study of the progression of long-term changes after early steroid withdrawal is needed [Heilman RL, et al. Impact of early conversion from tacrolimus to sirolimus on chronic allograft changes in kidney recipients on rapid steroid withdrawal. Transplantation 2012; 93:47–53].

March 2012 (Vol. 4, Number 3)