This retrospective multi-center study was conducted to evaluate the effect of PPI use on CV events and mortality in PD patients. We studied 904 PD patients from the Second Affiliated Hospital of Guangzhou Medical University and Zhujiang Hospital Affiliated to Southern Medical University from January 1, 2010 to December 31, 2016. Patients were divided into PPI group (Use of PPIs at baseline) and no-PPI group. Patients using PPI for more than 1 week continuously were included in the PPI group. Patients were exclude for the following reasons: age younger than 18 years or older than 80 years (n=22), PD was maintained for less than 3 months (n=21), missing data (n=33). In all, 829 patients were enrolled in the study, including 211 on PPI therapy and 618 not receiving PPI. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was warranted by the Institutional Review Board of two PD centers. Owing we had collected the existing medical records, written informed consent wasn’t required.
All patients were followed up until CV events or death, transferring to HD therapy, transferring to kidney transplantation, transferring of care to other centers, lost to follow up or censoring on December 31, 2017. The primary outcome was all-cause mortality, the second outcome was CV events. CVD are defined as recording any of the following conditions in the patient's medical records: coronary heart disease, coronary atherosclerotic heart disease, acute myocardial infarction, cardiac arrest, cerebrovascular accident, stroke, congestive heart failure.
The baseline demographic data included center, age, gender and comorbid (history of hypertension, diabetes, CVD and gastrointestinal bleeding). Baseline data were collected within 3 month of the initiation of PD. Clinical biochemical indicators included body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), medication history (including calcium channel blockers (CCB), angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB),βblockers, aspirin, statins), hemoglobin, creatinine, urea nitrogen, uric acid, fasting blood glucose (FBG), cholesterol, triglycerides, calcium, potassium, phosphorus, total Kt/v, residual renal function (RRF). Patients who reported current use of insulin or oral hypoglycemic agents and / or who had a clinical diagnosis of type 1 or type 2 diabetes mellitus were considered to have diabetes mellitus. Hypertension was recorded if the patient took antihypertensive drugs or had 2 separate blood pressure measurements ≥ 140/90mmHg.
Laboratory measurements were obtained using standard methods in the clinical laboratory. Total Kt/V were calculated using PD Adequest software 2.0 (Baxter, Deerfield, IL). Medicine use was recorded based on prescriptions. Patients returned to these centers for quarterly evaluation, and trained nurses interviewed the patients by telephone monthly to assess general conditions.
Continuous variables were described as means±standard deviations (SD) or median (25th-75th percentile), and categorical data were given as number (percentages). Comparisons of the variable between groups were performed using the t test for normally distributed variables and Mann-Whitney U test for skewed continuous variables. Differences among the two groups were tested using chi-square test for categorical variables. Mortality and incidence of CV events were calculated using the Kaplan-Meier curve and differences among distributions were assessed by log-rank test. Cox regression models were used to evaluate the relationship among PPI use with mortality and CV events in patients undergoing PD, initially without adjustment and subsequently adjusting for several groups of covariates. Inverse probability of treatment weighting (IPTW) analysis was applied to assess the influence of PPI use. IPTW analysis is obtained by using the propensity scores of all indicators before matching, and statistically adjusting the covariates to reduce the bias, thereby achieving randomization. Variables included in the IPTW analysis were center, age, sex, BMI, diabetes mellitus, hypertension, systolic pressure, history of CVD, history of gastrointestinal bleeding, ACEI / ARB use, βblcoker use, CCB use, aspirin use, statins use, hemoglobin, creatinine, urea nitrogen, cholesterol, triglycerides, uric acid, calcium, potassium, phosphorus and Kt/V, RRF.
In Cox regression models, time at risk was from study entry until CV events, death, transferring to HD therapy, transferring to kidney transplantation, transferring of care to other centers, or the end of study on December 31, 2017. Missing data were filled by miss Forest method. Statistical analysis are completed by SPSS 23.0 and R software(version R-3.6.2, www.r-project.org). All tests were performed bilaterally, and P < 0.05 was considered to be statistically significant.