PPI Use with MMF May Increase Acute Rejection Risk

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SAN DIEGO—Renal transplant recipients who use of proton pump inhibitors (PPIs) and mycophenolate mofetil (MMF) in the first year after transplantation may be at increased risk for allograft acute rejection, data presented at Kidney Week 2012 suggest.

Recent pharmacokinetic studies have shown that PPIs reduce exposure of mycophenolic acid (MPA), but the clinical significance of this drug-drug interaction on transplant outcomes has not been studied, according to researchers John P. Knorr, PharmD, and colleagues at Einstein Medical Center in Philadelphia. In a retrospective study, they evaluated the impact of PPI use on one-year rates of biopsy-proven acute rejection (BPAR) in 615 renal transplant recipients on MMF and steroids. Of these, 225 were prescribed PPIs and 390 were on standard acid-suppressive therapy with ranitidine.

BPAR occurred significantly more frequently in the PPI group than the ranitidine group (20% vs. 16.4%), a difference that translated into a 50% increased risk of BPAR associated with PPI use. The two groups were similar with respect to age, gender, cold ischemia time, HLA mismatch, donor age, cytomegalovirus status, and MMF dose at discharge.

At one year, PPI use did not affect BPAR type, BPAR grade, time to BPAR, graft function, and patient and graft survival.

It is possible that a reduction in MPA exposure contributed to the increased risk of BPAR in the first transplant year, the researchers concluded, adding that PPIs should be prescribed judiciously for kidney transplant patients on MMF.

Pankaj Jawa, MD, a transplant nephrology fellow who presented study findings, said the study's findings have changed practice in his institution's transplant nephrology department. For transplant patients on MMF who require medication for gastroesophageal reflux disease, doctors would try to avoid using PPIs and first prescribe H2-receptor antagonists.

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