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The use of proton pump inhibitors does not increase the risk of acute rejection after renal transplantation

Boekel, G.A.J. van, Kerkhofs, C.H.H., Logt, F. van de, Hilbrands, L.B.

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Background Mycophenolate mofetil (MMF), is the pro-drug of mycophenolic acid (MPA), which is formed after de-esterification of MMF in the stomach. Adequate exposure to MPA is associated with a decreased rate of acute rejection after renal transplantation. Several studies indicate that concomitant use of proton pump inhibitors (PPI) might impair the exposure to MPA due to incomplete de-esterification of MMF at elevated gastric pH. This could result in an increased risk of acute rejection. In our centre, renal transplant patients are prophylactically treated with a PPI (pantoprazole) or an H2 antagonists (ranitidine) for at least three months after renal transplantation.

 

Aim To investigate whether MMF-treated renal transplant patients who concomitantly used pantoprazole, had a higher risk of acute rejection within the first 3 months after transplantation than those who used ranitidine.

 

Patients and methods We performed a retrospective study in adult patients, who underwent a kidney transplantation between January 2007 and December 2011. Their immunosuppressive therapy consisted of steroids, tacrolimus and MMF. Exclusion criteria were a history of bowel surgery, the use of a phosphate binder, the switch between PPI and H2 antagonist, and the combined use of PPI and H2 antagonist.

 

Results 207 patients were included: 126 with pantoprazole and 81 with ranitidine. Both groups were comparable regarding age, body weight, dose of prednisone and tacrolimus, retransplantations, and donor type. In the first 3 months after transplantation, the cumulative dose of MMF was 142,894±17,718 mg in patients with pantoprazole and 144,289±18,097 mg in patients with ranitidine (NS). The number of patients with a clinical diagnosis of acute rejection within three months after transplantation did not differ between both groups: 26 (19.5%) in the pantoprazole group versus 15 (20,0%) in the ranitidine group. There was also no difference in the number of patients with biopsy-proven acute rejection (13 [10,0%] versus 7 [9,1%]). Logistic regression analysis did not reveal a correlation between the cumulative dose of pantoprazole and the risk of acute rejection. Three months after renal transplantation, the mean estimated glomerular filtration rate did not differ significantly: 49.4±12.5 ml/min/1.73m2 versus 50.7±12.5 ml/min/1.73m2, respectively.

 

Conclusions There was no evidence for an increased incidence of acute rejection in patients who concomitantly use MMF and pantoprazole.