Chronic kidney disease progression with proton pump inhibitors versus H2 receptor antagonists in NSAID users

Clinical evidence comparing the renal impact of proton pump inhibitors (PPIs) and Histamine-2 receptor antagonists (H2RAs) in patients with chronic kidney disease (CKD) receiving traditional non-steroidal anti-inflammatory drugs (tNSAIDs) is lacking. We evaluated CKD progression risk associated with PPIs versus H2RAs within a tNSAID-treated cohort to inform clinical prescribing.

This retrospective cohort study used South Korean nationwide claims data (2018-2023). Stabilized inverse probability of treatment weighting (SIPTW) balanced the cohorts. Restricted cubic spline Cox regression addressed non-linear associations between CKD progression and cumulative exposure to tNSAIDs and acid suppressants (PPIs or H2RAs). Sensitivity analyses addressing unspecified CKD stages confirmed the robustness of the primary findings.

Among 141 093 tNSAID initiators with CKD prescribed PPIs (n = 5315) or H2RAs (n = 7112), PPIs were associated with higher CKD progression risk than H2RAs (adjusted hazard ratio [aHR] 1.38, 95% CI 1.10-1.74). Baseline comorbidities-hypertension (aHR 2.03, 95% CI 1.37-2.99]), diabetes (1.69 [1.29-2.21]), and a history of kidney disease (1.43 [1.13-1.81])-and prior diuretic use (2.00 [1.56-2.58]) were associated with increased risk of CKD progression. In contrast, dapagliflozin or empagliflozin use was protective (0.49 [0.27-0.89]). The risk of CKD progression for PPIs relative to H2RAs was most pronounced in females, those with CKD stage 3, patients aged ≥71 years, and those with 1-15 days of treatment (all P < .05).

Our findings suggest that H2RAs may be associated with a lower risk of CKD progression than PPIs in tNSAID users with CKD, potentially offering a safer alternative when PPI therapy is not indispensable.