The Effects of Pantoprazole on Kidney Outcomes
Bibliographic record
Abstract
Key Points In this post hoc analysis of a randomized controlled trial, the proton pump inhibitor pantoprazole led to a faster rate of eGFR decline as compared with placebo. Additional studies are needed to determine the effect of proton pump inhibitors on those at higher risk of adverse kidney outcomes. Background Observational studies have found an association between proton pump inhibitor use and worsening kidney function. It is unclear whether these associations are causal. We conducted post hoc analyses to determine the effect of pantoprazole on kidney function using data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, a 17,598-participant randomized trial comparing pantoprazole (8791) with placebo (8807). Methods The primary outcome was the rate of eGFR change. Rate of eGFR change was based on the two eGFR measures available: the eGFR at randomization and at the open-label extension study that enrolled at trial conclusion. Secondary outcomes included incident CKD (defined by eGFR <60 ml/min per 1.73 m 2 at open-label extension or case report forms) as well as AKI, acute nephritis, and nephrotic syndrome. Results Eight thousand nine hundred ninety-one of the 17,598 participants randomized to pantoprazole/placebo (51%) had eGFR recorded at baseline and open-label extension enrollment and were included in the rate of eGFR change population (mean age 67 [SD 8] years, 22% female, mean baseline eGFR 75 [SD 17.5] ml/min per 1.73 m 2 ). The mean duration between randomization and open-label extension eGFR was 3.3 (SD 0.8) years. The placebo rate of eGFR change was −1.41 (SD 4.45) ml/min per 1.73 m 2 per year. The pantoprazole rate of eGFR change was −1.64 (SD 4.47) ml/min per 1.73 m 2 per year. In adjusted analyses, pantoprazole had a 0.27 ml/min per 1.73 m 2 per year greater decline in eGFR (95% confidence interval [CI], 0.11 to 0.43). The odds ratio for the effect of pantoprazole on incident CKD was 1.11 (95% CI, 0.98 to 1.25) and on AKI was 0.89 (95% CI, 0.65 to 1.21). There were five nephrotic syndrome outcomes recorded and one event of acute nephritis. Conclusions In this post hoc analysis of the COMPASS trial, pantoprazole resulted in a statistically significant greater rate of eGFR decline as compared with placebo. Clinical Trial registry name and registration number: Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS), NCT01776424.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.025 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.007 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.011 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".