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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.