Comparing safety of proton‐pump inhibitors versus H2‐receptor antagonists in kidney transplant recipients: A systematic review and meta‐analysis

Abstract

Multiple studies have been conducted to compare the safety of proton-pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) as acid-suppressive treatment in kidney transplant recipients with conflicting results. This systematic review and meta-analysis aimed to evaluate the risk of adverse effects in kidney transplant patients receiving PPIs compared to those treated with H2RAs. A systematic search was performed on the databases from inception to June 2021. The treatment effects were expressed as odds ratio (OR), weighted mean differences (WMD) and their 95% confidence intervals (CI) and pooled by a random-effects model. Eight studies, consisting 4,844 patients, were included. Patients were followed for a mean duration of 23.57months after transplantation. Compared with H2RAs, PPIs exposure was associated with similar rate of biopsy-proven acute rejection (BPAR) (OR= 1.05, 95% CI 0.83-1.34, p=0.67), mortality (OR=1.31, 95% CI 0.56-3.07, p=0.533), graft loss (OR=1.06, 95% CI 0.59-1.93, p=0.842), Clostridioides difficile infection (OR=1.37, 95% CI 0.49-3.85, p=0.545) and pneumonia (OR=1.83, 95% CI 0.95-3.52, p=0.072). The estimated glomerular filtration rate (eGFR) at 12months was lower in patients who received PPIs than those treated with H2RAs (WMD=-1.01, 95% CI -1.89 to -0.12ml/min/1.73m2 , p=0.02). The PPI-treated kidney transplant patients experienced higher rate of antibody-mediated rejection (AMR) (OR=1.87, 95% CI 1.03-3.04, p=0.039) and hypomagnesemia (OR=2.16, 95% CI 1.46-3.20, p˂0.001). Compared with H2RAs, PPIs were not associated with higher risks of BPAR, mortality, graft loss or infection-related outcomes. However, taking PPIs was associated with higher rates of AMR and hypomagnesemia, and lower eGFR at one year after transplantation. Further well-controlled studies are needed to assess the impact of acid-suppressive strategy on long-term outcomes in KTRs.