Background. Proton pump inhibitors (PPIs) are commonly prescribed post-kidney transplantation and often continued thereafter. However, numerous studies have reported complications associated with PPI use, particularly nephrotoxicity affecting native kidneys. Nonetheless, data regarding PPI use in kidney transplantation remains limited.
Methods. We conducted a retrospective analysis of all kidney transplant recipients at Nantes University Hospital between 01/01/2000 and 31/12/2020. To assess the specific effects of PPIs, we employed time-dependent survival analysis to investigate the association between PPI presence and various endpoints. The primary endpoint was patient and graft survival. Secondary endpoints included biopsy-proven rejection, all-cause infections, and gastrointestinal bleeding complications. Analyses were conducted using a multivariate Cox model.
Results. A total of 2799 patients were included in the analysis, with a median follow-up time of 6 years. In time-dependent multivariate analysis, PPI use was significantly associated with patient survival (HR = 1.46; 95% CI [1.25;1.69]). Specifically, PPI use increased the risk of death due to infectious complications (HR = 2.01; 95% CI [1.34; 3.02]) and cardiovascular events (HR = 1.42; 95% CI [1.01;1.99]) in a time-dependent manner. Additionally, PPI use impacted allograft survival (HR = 1.96; 95% CI [1.66; 2.32]) despite having no effect on allograft rejection (HR = 0.97; 95% CI [0.78;1.20]). Furthermore, PPI use was not associated with a reduction in gastrointestinal complications (HR = 1.15; 95% CI [0.81;1.64]) and did not affect the occurrence of the first infectious complication (HR = 1.07; 95% CI [0.95;1.20]) or the first cardiovascular event (HR = 1.11; 95% CI [0.90;1.38]).
Conclusion. PPIs significantly worsen patient survival due to increased severity of infectious and cardiovascular complications. PPI use also impacts allograft survival without increasing rejection episodes, possibly through an increase in allograft arteriosclerosis. Therefore, the prescription of PPIs should be strictly limited to identified indications and deprescribed as often as possible due to the associated risk of severe side effects.