title: Concomitant proton pump inhibitors with mycophenolate mofetil and the risk of rejection in kidney transplant recipients.
abstract: BACKGROUND
  Recent pharmacokinetic studies have demonstrated that proton pump inhibitors (PPI) reduce exposure of mycophenolic acid. However, the clinical significance of this drug-drug interaction on transplantation outcomes has not been determined.
  
  
  METHODS
  This was a retrospective cohort study in kidney transplant recipients who were prescribed rabbit antithymocyte globulin, calcineurin inhibitor, mycophenolate mofetil, and steroids. We evaluated the impact of PPI use on the 1-year rates of biopsy-proven acute rejection (BPAR).
  
  
  RESULTS
  Two hundred thirteen patients who were prescribed PPI were compared with 384 patients who were on standard acid-suppressive therapy with ranitidine. BPAR occurred in similar rates in both groups (15% vs. 12%; P=0.31). In a multivariable analysis, black race was associated with a higher risk of rejection (risk ratio [RR], 2.38; 95% confidence interval [CI], 1.41-4.03). While controlling for rejection risk factors, PPI exposure was associated with an increased risk of rejection in black patients (RR, 1.93; 95% CI, 1.18-3.16) but not in non-black patients (RR, 0.54; 95% CI, 0.19-1.49). At 1 year, BPAR type, BPAR grade, patient and graft survival, graft function, and time to BPAR were not associated with PPI exposure.
  
  
  CONCLUSIONS
  In this retrospective study, PPI use in the first transplant year was associated with an increased risk for BPAR in black patients but not in non-black patients. It is possible that a reduction in mycophenolic acid exposure contributed to the increased risk.
authors.affiliation: 1 Department of Pharmacy, Einstein Medical Center, Philadelphia, PA. 2 Department of Statistics, Einstein Medical Center, Philadelphia, PA. 3 Department of Medicine, Einstein Medical Center, Philadelphia, PA. 4 Department of Surgery, Einstein Medical Center, Philadelphia, PA. 5 Address correspondence to: John P. Knorr, Pharm.D., B.C.P.S., Department of Pharmacy, Einstein Medical Center, 5501 Old York Road, Philadelphia, PA.
authors.forename: John P
authors.initials: JP
authors.lastname: Knorr
authors.forename: Mariel
authors.initials: M
authors.lastname: Sjeime
authors.forename: Leonard E
authors.initials: LE
authors.lastname: Braitman
authors.forename: Pankaj
authors.initials: P
authors.lastname: Jawa
authors.forename: Radi
authors.initials: R
authors.lastname: Zaki
authors.forename: Jorge
authors.initials: J
authors.lastname: Ortiz
mesh_terms: D000328:Adult; D000368:Aged; D044383:Black People; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000208:ethnology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D044469:Racial Groups; D012189:Retrospective Studies; D012307:Risk Factors; D014180:Transplantation; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D054328:Proton Pump Inhibitors; D009173:Mycophenolic Acid