Cohort studyindependent cross-checkabstract checked★ key study I-PPI-111 in-depth review
No extra kidney decline with PPIs vs H2 blockers in Spain
Proton Pump Inhibitor Use and Worsening Kidney Function: A Retrospective Cohort Study Including 122,606 Acid-Suppressing Users.
Overview
González-Pérez A et al.. J Gen Intern Med 2025 · PMID 39627545 · DOI 10.1007/s11606-024-09213-8
In 122,606 new users, kidney function worsened equally often with PPIs and ranitidine after accounting for differences between users.
Does the study support the specific claim? No · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Compare kidney outcomes of PPI and H2RA starters.
- How was the study done?
Population cohort.
- How many people, animals or samples were studied?
122,606 people in Aragon.
- What was actually found?
Adjusted HR 0.99 for eGFR<60; less AKI with PPI.
- How large was the observed effect?
HR 0.99 (0.66-1.48).
- What do the results mean in everyday life?
PPIs are unlikely to be a major cause of kidney decline.
- What are the study's limitations?
Few H2RA users; short follow-up.
- What does it say about Elawady's specific claim?
Contradicts PPIs causing CKD.
- Do the results apply to Germany and Europe?
Directly applicable.
- What can explicitly not be concluded from this study?
Cannot exclude small long-term effects.
Scientific in-depth review
1. Full reference
- Authors
- González-Pérez A et al.
- Journal
- J Gen Intern Med
- Year
- 2025
- Identifier
- PMID 39627545 DOI 10.1007/s11606-024-09213-8
- Verification
- verified – PubMed efetch 2026-10-26 + Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
No conflicts of interest declared
2. Research question
Do PPI initiators have a higher risk of worsening kidney function or AKI than H2RA initiators?
3. Study design and population
- Study design
- Cohort study – Retrospective population-based new-user active-comparator cohort (BIGAN, Aragon)
- Population
Initiators of PPIs or H2RAs with preserved renal function
- Country
Spain
- Period
2015-2021
- Sample size
119,520 PPI and 3086 H2RA initiators
- Inclusion and exclusion criteria
Preserved kidney function at baseline
4. Methods and endpoints
- Exposure / intervention
PPI (e.g., omeprazole)
- Comparator
H2RA (ranitidine)
- Endpoints
Worsening kidney function (eGFR<60, sCr doubling, eGFR fall 30-50%, ESRD); AKI
- Statistical methods
Cox regression adjusted for confounders
5. Actual results
- Results
Crude incidence of eGFR<60 higher with omeprazole (31.2/1000 PY) than ranitidine (18.7), but adjusted HR 0.99 (0.66-1.48). AKI lower with omeprazole: HR 0.54 (0.42-0.70).
- Absolute risks
Crude IR 31.2 vs 18.7 per 1000 PY (eGFR<60); not different after adjustment
- Authors' conclusion
No clinically relevant difference in worsening kidney function between PPI and H2RA initiators.
6. Strengths
- Active comparator
- Laboratory-defined outcomes
7. Weaknesses
- Small H2RA group
- Short follow-up (up to ~6 y)
- Observational
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Confounding by indication reduced by active comparator.
9. Assessment of the statistical interpretation
Crude difference vanishes after adjustment: a sign that baseline differences drive crude associations (stats/C-PPI-01_kidney_mortality.py).
10. Relevance to the specific claim
European active-comparator data not supporting a kidney-damaging effect of PPIs.
11. Independent contrary findings
Xie 2017 (A-PPI-02) and Ang 2024 (I-PPI-112) report higher CKD risk vs H2RA.
12. Transferability to Germany and Europe
Directly applicable.
13. Overall methodological judgement
Adds to uncertainty about causality of the CKD signal.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | low |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | mixed |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Long-term (>5 y) effects.