Non-indicated initiation of proton pump inhibitor and risk of adverse outcomes in patients with underlying chronic kidney disease: a nationwide, retrospective, cohort study

Abstract

Objective: Evidence related to the risk of kidney damage by proton pump inhibitor (PPI) initiation in patients with 'underlying' chronic kidney disease (CKD) remains scarce, although PPI use is generally associated with acute interstitial nephritis or incident CKD. We aimed to investigate the association between PPI initiation and the risk of adverse outcomes in patients with CKD in the absence of any deterministic indications for PPI usage.

Design: Retrospective observational study.

Setting: Korea National Health Insurance Service database from 2009 to 2017.

Participants: A retrospective cohort of new PPI and histamine H₂-receptor antagonists (H2RA) users among people with CKD. Patients with a history of gastrointestinal bleeding or those who had an endoscopic or image-based upper gastrointestinal tract evaluation were excluded.

Primary and secondary outcome measures: The study subjects were followed to ascertain clinical outcomes including mortality, end-stage kidney disease (ESKD), myocardial infarction and stroke. The HRs of outcomes were measured using a Cox regression model after adjusting for multiple variables. We applied an inverse probability of treatment weighting (IPTW) model to control for residual confounders.

Results: We included a total of 1038 PPI and 3090 H2RA users without deterministic indications for treatment. IPTW-weighted Cox regression analysis showed that PPI initiation was more significantly associated with a higher ESKD risk compared with that of H2RA initiation (adjusted HR 1.72 (95% CI 1.19 to 2.48)), whereas the risks of mortality or cardiovascular outcomes were similar between the two groups. In the subgroup analysis, multivariable Cox regression analysis showed that the association between PPI use and the progression to ESKD remained significant in non-diabetic and low estimated glomerular filtration rate (<60 mL/min/1.73 m²) groups (adjusted HR 1.72 (95% CI 1.19 to 2.48) and 1.63 (95% CI 1.09 to 2.43), respectively).

Conclusions: Initiation of PPI administration may not be recommended in patients with CKD without deterministic indication, as their usage was associated with a higher risk of ESKD.

Keywords: Acute renal failure; Adult nephrology; Chronic renal failure; End stage renal failure.