(P-009) Proton Pump Inhibitors and Risk of End Stage Renal Disease in Patients with Chronic Kidney Disease

Background: Proton pump inhibitor (PPI) use has been shown to be associated with higher risk of incident chronic kidney disease (CKD) in general population. CKD patients are population with higher risk of developing end-stage renal disease (ESRD). A few studies had found increased risk of progression to ESRD in CKD patients with use of PPI. However, current evidence remains scarce.

Objectives: To evaluate the association between use of PPI and risk of ESRD in CKD population.

Methods: We identified newly diagnosed CKD patients between 2003 and 2013 from a random-selected sample of a million beneficiaries under the National Health Insurance coverage in Taiwan. We defined 365 days after CKD diagnosis day as the index date and identified incident users of PPI, histamine-2-receptor antagonist (H2RA) and none-users based on exposure during the landmark period. Only adults without ESRD were included in our study. Three groups of patients were followed until occurrence of ESRD, death or end of study (i.e., 31 Dec 2013). ESRD comprised initiation of hemodialysis or kidney transplantation. To mitigate confounding, covariates including demographics, gastrointestinal diseases related to acid-suppressant use, cardiovascular diseases, other comorbidities, concurrent medications and general health resource utilization were collected from baseline to generate a propensity score for every patient. We further applied inverse probability treatment weighting with stabilized weights to estimate average treatment effects PPI and H2RA compared with non-use group. In consideration of death as competing event, we applied subdistribution hazard model with Cox regression to obtain the hazard ratio and 95% confidence interval (95%CI).

Results: 463 PPI, 1511 H2RA and 6932 non-users were included in this study, respectively. Compared with H2RA and non-user group, PPI group were older (mean age of 71 vs. 68 and 67 for H2RA and non-user group) and contained higher proportion of patients with history of GERD, ulcer diseases, GI bleeding, diabetes, hypertension and heart failure. After a mean follow-up of 3.1 years, incidence rate of ESRD were calculated to be 56.1, 41.2 and 41.9 per thousand patient-years for PPI, H2RA and non-user group. Results of propensity score IPTW showed hazard ratios of ESRD for PPI and H2RA were 1.03 (95%CI 0.78 to 1.34) and 0.96 (95%CI 0.82 to 1.13) respectively when compared to non-user group.

Conclusions: We found use of PPI and H2RA did not increase risk of ESRD after controlling important confounders and consideration of competing risk of death. Positive findings from previous researches might be explained by factors other than PPI use.