Impact of Perioperative Proton Pump Inhibitors on Renal Cancer Progression. A Retrospective Study

ABSTRACT Background Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. Metastatic disease causes most deaths. We investigated the association between ATP4A gene status and survival following nephrectomy. ATP4A encodes H + /K + ATPase, targeted by proton pump inhibitors (PPIs). We also examined how perioperative use of these drugs affects cancer progression post‐surgery. Methods Using a publicly available database, we employed in silico analysis to investigate the association between the ATP4A gene and recurrence‐free survival and overall survival. After receiving institutional review board approval from the University of Texas‐MD Anderson Cancer Center (#2020‐0380), we conducted a retrospective analysis to investigate the association between perioperative PPIs use and progression of nonmetastatic ccRCC. We performed a propensity score analysis and utilized inverse probability of treatment weighting to balance potential discrepancies between exposure groups. A Cox proportional hazards model, weighted by inverse probability of treatment weighting, was subsequently fitted for multivariable analysis. Results ATP4A gene expression analysis showed that high tumor levels were associated with a significant reduction in overall survival. The analysis included a total of 1775 patients with ccRCC. After propensity matching, the analysis revealed that the use of perioperative PPIs was not independently associated with a worse oncological prognosis following nephrectomies. Conclusion Elevated ATP4A gene expression correlates with reduced survival, while perioperative PPI use shows no significant impact on survival outcomes.