The Association Between Proton Pump Inhibitors And All-cause Mortality As Well As New-onset Cardiovascular Events In Peritoneal Dialysis Patients

Background: Proton pump inhibitors(PPIs)were commonly prescribed drugs in clinical.Studies had found that 25% to 70% of patients taking PPIs do not have the appropriate indications.PPI use had been confirmed to be related to a variety of adverse events in the general population,such as dementia,fractures,hyper-magnesemia,vitamin B12 deficiency,pneumonia,cardiovascular(CV)events,and death.In addition,long-term PPI use might increase the probability of adverse kidney prognosis and accelerate the deterioration of chronic kidney disease.PPI use was associated with poor prognosis of hemodialysis patients,but it was rarely reported in peritoneal dialysis(PD)patients.Objectives: To investigate the relationship between PPIs and all-cause mortality as well as new-onset cardiovascular events in peritoneal dialysis patients.Methods: This was a retrospective study involving regular peritoneal dialysis patients from two hospitals.Nonparametric and chi-square tests were used to compare the differences in baseline data between the two groups.Multivariate Logistic regression model was used to find out risk factors associated with all-cause mortality and new-onset cardiovascular events in peritoneal dialysis patients.Kaplan-Meier curves were used to identify the incidence of adverse outcomes(all-cause mortality and new-onset cardiovascular events),and the multivariate COX regression analysis was applied to analyze hazard ratio(HR)for adverse outcomes in different groups.Finally,we performed inverse probability of treatment weighted(IPTW)method to verify the results of Kaplan-Meier curve and multivariate COX regression analysis.Forest plot was used to represent the relationship between PPIs and all-cause mortality as well as new-onset cardiovascular events in each subgroup.Results: A total of 904 patients were collected in the study and 75 were excluded after screening,and 829 patients were finally enrolled,including 211 patients on PPI treatment and 618 patients not taking PPIs.During follow-up,162 deaths and 102new-onset cardiovascular events were recorded.Kaplan-Meier curve showed that all-cause mortality(log rank 5.55,P=0.018)and the incidence of new-onset cardiovascular events(log rank 5.07,P=0.024)were significantly higher in the group which taking PPIs.Multivariate COX regression analysis and COX regression analysis after IPTW suggested that PPI use was independently associated with higher all-cause mortality(HR=1.33,95%CI=1.07-1.65,P=0.010)and new-onset cardio-vascular events(HR=1.81,95%CI =1.38-2.38,P<0.001).Forest plot showed that no matter in the diabetes,gender,and age subgroups,there is no interaction between PPI use and poor prognosis(all-cause mortality and new-onset cardiovascular events)in patients with peritoneal dialysis.Conclusions: PPI use was associated with higher all-cause mortality and the incidence of new-onset cardiovascular events in peritoneal dialysis patients.Clinicians are supposed to be more careful when using PPIs and need to master the indications and treatments more rigorously in peritoneal dialysis patients.