Impact of Acid Suppression Therapy on Renal and Survival Outcomes in Patients with Chronic Kidney Disease: A Taiwanese Nationwide Cohort Study

Abstract

Histamine-2-receptor antagonist (H2RA) has shown beneficial effects on the kidney, heart, and sepsis in animal models and on the heart and COVID-19 infection in clinical studies. However, H2RAshave been used as a reference in most epidemiological studies examining the association of proton pump inhibitors (PPI) with outcomes. Therefore, we aimed to evaluate the effect of H2RA on renal and survival outcomes in chronic kidney disease (CKD) patients. We used a Taiwanese nationalhealth insurance database from 2001 to 2016 to screen 45,767 CKD patients for eligibility. We identified new users of PPI (n = 7121), H2RA (n = 48,609), and users of neither PPI nor H2RA (as controls) (n = 47,072) during follow-up, and finally created 1:1:1 propensityscore-matchedcohorts; each cohort contained 4361 patients. Participants were followed up after receivingacid-suppression agents or on the corresponding date until the occurrence of end-stage renal disease (ESRD) in the presence of competing mortality, death, or through the end of 2016. Compared toneither users, H2RAand PPI users demonstrated adjusted hazard ratios of 0.40 (95% confidence interval, 0.30-0.53) for ESRDand 0.64 (0.57-0.72) for death and 1.15 (0.91-1.45) for ESRD and 1.83 (1.65-2.03) for death, respectively. A dose-response relationship betweenH2RA use with ESRD and overall, cardiovascular, and non-cardiovascular mortality was detected. H2RA consistently provided renal and survival benefits on multivariable stratified analyses and multiple sensitivity analyses. In conclusion, dose-dependent H2RA use was associated with a reduced risk of ESRD and overall mortality in CKD patients, whereas PPI use was associated with an increased risk of overall mortality, not in a dose-dependent manner.

Keywords: CKD; ESRD; dose-response relationship; histamine-2-receptor antagonist; mortality; proton pump inhibitor.

Figure 1

Flow diagram of the enrollment process. Abbreviations: CKD, chronic kidney disease; ESRD, end-stage renal disease; H2RA, H2-receptor antagonist; PPI, proton pump inhibitor.