Meta-analysisindependent cross-checkabstract checked I-PPI-112 standard review
PPIs linked with chronic kidney disease in pooled studies
Association between Proton Pump Inhibitor Use and Risk of Incident Chronic Kidney Disease: Systematic Review and Meta-Analysis.
Overview
Ang SP et al.. Biomedicines 2024 · PMID 39061988 · DOI 10.3390/biomedicines12071414
Pooling 12 observational studies, PPI users had about 26% higher relative risk of developing chronic kidney disease.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Pool studies on PPIs and CKD.
- How was the study done?
Meta-analysis.
- How many people, animals or samples were studied?
700,125 participants.
- What was actually found?
HR 1.26 vs non-users; 1.34 vs H2RA.
- How large was the observed effect?
1.26 (1.16-1.38).
- What do the results mean in everyday life?
Association is consistent but may reflect sicker users.
- What are the study's limitations?
Observational only.
- What does it say about Elawady's specific claim?
Supports the association, not causation.
- Do the results apply to Germany and Europe?
Moderate.
- What can explicitly not be concluded from this study?
Cannot prove PPIs damage kidneys.
Scientific in-depth review
1. Full reference
- Authors
- Ang SP et al.
- Journal
- Biomedicines
- Year
- 2024
- Identifier
- PMID 39061988 DOI 10.3390/biomedicines12071414
- 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 declared
2. Research question
Is PPI use associated with incident CKD?
3. Study design and population
- Study design
- Meta-analysis – Systematic review and meta-analysis of observational studies
- Population
Adults in 12 observational studies
- Country
International
- Period
Search to March 2024
- Sample size
12 studies; 700,125 participants
- Inclusion and exclusion criteria
Studies comparing PPI with non-use or H2RA
4. Methods and endpoints
- Exposure / intervention
PPI
- Comparator
Non-use; H2RA
- Endpoints
Incident CKD
- Statistical methods
DerSimonian-Laird random effects; leave-one-out
5. Actual results
- Results
Incident CKD vs non-users HR 1.26 (1.16-1.38); vs H2RA HR 1.34 (1.13-1.59); robust in leave-one-out analysis.
- Absolute risks
Not reported
- Authors' conclusion
PPI use is associated with higher CKD incidence; judicious use advised.
6. Strengths
- Includes active-comparator analyses
7. Weaknesses
- Observational studies only
- Overlaps with archive-cited cohorts (A-PPI-01/02)
- No formal certainty rating in abstract
8. Risk of bias
- Orienting tool
- AMSTAR 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Pooled confounded estimates; overlap with included primary studies.
9. Assessment of the statistical interpretation
Consistent association of modest size; pooled observational estimate overlaps the COMPASS CKD CI (stats/C-PPI-01_kidney_mortality.py). Not independent of A-PPI-01/02.
10. Relevance to the specific claim
Supports that the CKD association is reproducible; does not establish causation.
11. Independent contrary findings
Gonzalez-Perez 2025 (I-PPI-111), COMPASS (I-PPI-01).
12. Transferability to Germany and Europe
Moderate.
13. Overall methodological judgement
Confirms association, not cause.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | high |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | mixed |
| Regional transferability | moderate |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Causal designs.