John P Knorr1, Mariel Sjeime, Leonard E Braitman, Pankaj Jawa, Radi Zaki, Jorge Ortiz. 1. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Kevin Schulte; Jodok Püchel; Katrin Schüssel; Christoph Borzikowsky; Ulrich Kunzendorf; Thorsten Feldkamp Journal: Transplant Direct Date: 2019-06-27
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