The Effects of Pantoprazole on Kidney Outcomes: Post Hoc Observational Analysis from the COMPASS Trial

Background: Observational studies have found an association between proton pump inhibitor (PPI) 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 (8,791) to placebo (8,807). Methods: The primary outcome was the rate of change of estimated glomerular filtration rate (eGFR). 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 chronic kidney disease (CKD) (defined by eGFR <60 ml/min/1.73 m(2) at open label extension or case report forms) as well as acute kidney injury (AKI), acute nephritis, and nephrotic syndrome. Results: 8,991 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/1.73 m(2)). The mean duration between randomization and open label extension eGFR was 3.3 years. The placebo rate of eGFR change was -1.41 (SD 4.45) ml/min/1.73 m(2) per year. The pantoprazole rate of eGFR change was -1.64 (SD 4.47) ml/min/1.73 m(2) per year. In adjusted analyses pantoprazole had a 0.27 ml/min/1.73 m(2) per year greater decline in eGFR (95% 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 5 nephrotic syndrome outcomes recorded and 1 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 to placebo. The clinical importance of this is uncertain.