Everolimus in liver transplant patients preserves GFR. PROTECT study – 35 month update.

Long term exposure to calcineurin inhibitors (CNI) is nephrotoxic. It is believed that these drugs are therefore responsible for the significant number of patients with non-renal solid organ transplants that subsequently develop CKD. This was best seen in the NEJM paper by Ojo et al where 7-21% of solid organ recipients developed CKD by 5 years post transplant. Subsequently the TRY study revealed that 58% of liver transplant recipients develop CKD stage 3 by 60 months post transplant. It would then make sense to use alternative immunosuppressive agents in solid organ transplant recipients to preserve kidney function – as long as the drug does not compromise graft outcome. The PROTECT study aimed to assess just that.

During a plenary session at the ATC, Dr. H. Schliff from University Hospital Regensburg, Germany, presented 35 month follow up results of a multicenter, open labeled, prospective randomized controlled trial which compared kidney function in liver transplant patients maintained on CNI versus those converted to everolimus 4 weeks post transplant. Their one year published data revealed the GFR in patients on everolimus to be about 8 mL higher than those maintained on CNI. Of those 203 patients, 33 patients on everolimus and 27 patients on CNI completed the extension study. Baseline characteristics of the two groups were similar. At the end of the study, there was about a 10 mL difference in GFR between everolimus group and the CNI group. Due to low power, the difference was not significant using the MDRD equation, but was when the Nankivill formula was used. Furthermore graphic display of baseline and follow up revealed GFR to remain stable in patients on everolimus while it deteriorated in the CNI group. Equally important was that liver transplant outcome, including graft survival and rejection, were the same in both groups. There was slightly more anemia and hyperlipidemia in the everolimus group but it was generally well tolerated.

Some audience criticisms: It is possible that the GFR was worse in the CNI group because of the drugs hemodynamic effects. The lack of hard endpoints such as need for dialysis makes this hard to argue against, however, there did seem to be some deterioration of kidney function in the CNI group as opposed to preserved GFR in the everolimus group.

The number of solid organ transplant recipients is increasing as is their long term graft survival. This study offers some potential solutions to the problem of CKD in liver transplant patients.

Post written by Dr. Vinay Nair, eAJKD Advisory Board member.

Check out all of eAJKD’s coverage of the 2013 American Transplant Congress.