Clinical

Enterocyte protein predicts acute rejection of liver transplant

Last Updated: 2006-02-23 12:34:09 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Elevated expression of a protein called MDR1 in enterocytes is a risk factor for acute cellular rejection of living-donor liver transplants, according to a report in the January issue of Clinical Pharmacology & Therapeutics.

MDR1 contributes to the metabolism of tacrolimus, and measuring its expression can help with tacrolimus dosing, the report suggests.

The findings are based on an analysis of MDR1 mRNA in 164 intestinal mucosa specimens obtained during liver transplantation.

Consistent with previous reports, a low trough level of tacrolimus soon after surgery was associated with acute cellular rejection, senior author Dr. Ken-ichi Inui, from Kyoto University in Japan, and colleagues note. Specifically, with a level below 7 ng/mL, the rate of rejection was 45.1%, whereas with higher levels, the rate was 22.9% (p = 0.004).

Elevated levels of MDR1 mRNA more than doubled the risk of acute cellular rejection before postoperative day 10, the report indicates. In addition, such levels were associated with a 7.4-fold increased risk of death during the first postoperative year.

The degree of MDR1 mRNA expression was inversely linked to the tacrolimus concentration/oral dose ratio in the first 4 days after transplantation, the authors note.

"Obtaining a sufficient tacrolimus blood level via this molecular information-based initial dosage adjustment may enable the episode of acute cellular rejection after liver transplantation to be reduced," Dr. Inui's team concludes.

Clin Pharmacol Ther 2006;79:90-102.