Effects of Proton Pump Inhibitors on Patient Survival in Patients Undergoing Maintenance Hemodialysis

Abstract

Data to draw definite conclusions regarding the association between proton pump inhibitor (PPI) and all-cause mortality in patients undergoing hemodialysis (HD) remain insufficient. The object of this retrospective study was to assess the impact of PPIs on patient survival within a substantial cohort of individuals receiving maintenance HD. To achieve this, the study employed laboratory and clinical data sourced from the 4th, 5th, and 6th National HD Quality Assessment Programs. The programs included patients undergoing maintenance HD (n = 54,903). Based on the PPI prescription data collected over the 6-month HD quality assessment, the patients were categorized into three groups: Group 1, comprising individuals with not prescription; Group 2, consisting of patients prescribed PPIs for less than 90 days; and Group 3, comprising patients prescribed PPIs for 90 days or more. The respective number of patients in Groups 1, 2, and 3 was 43,059 (78.4%), 5065 (9.2%), and 6779 (12.3%), respectively. Among the study groups, the 5-year survival rates were as follows: Group 1-70.0%, Group 2-68.4%, and Group 3-63.0%. The hazard ratio for Group 3 was 1.09 (95% CI, 1.04 to 1.15; p < 0.001) and 1.10 (95% CI, 1.03 to 1.18; p = 0.007) compared to Groups 1 or 2 based on multivariable analysis. Multivariable analyses revealed a lower rate of patient survival in Group 3 compared to the other groups, while Groups 1 and 2 exhibited similar patient survival rates. Our study revealed a significant association between long-term PPI usage and increased mortality among patients undergoing HD. However, distinct trends were observed in subgroup analyses. The association between long-term PPI usage and mortality was prominent in patients who did not have a high gastrointestinal burden or comorbidities. Meanwhile, this association was not observed in patients who did have a high gastrointestinal burden or comorbidities.

Keywords: dialysis; hemodialysis; mortality; proton pump inhibitor.

Figure 1

Patient survival curves.

Figure 2

HRs and 95% CIs by subgroups, visualized in forest plots. (A) Univariate and (B) multivariable Cox regression analyses. The analyses were adjusted according to underlying cause of end-stage renal disease, vascular access type, Charlson Comorbidity Index score, age, gender, hemodialysis vintage, ultrafiltration volume, systolic blood pressure, diastolic blood pressure, Kt/V_urea, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, the use of anti-hypertensive drugs, aspirin, and statin. Abbreviations: adHR, adjusted hazard ratio; CI, confidence interval; DM, diabetes mellitus; G1, Group 1; G2, Group 2; G3, Group 3; ref, reference; unHR, unadjusted hazard ratio; Yr, years.