Association between Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Acute Kidney Injury: A Nested Case-Control Study.

KEY POINTS

This is the first study to use a large database of patients with cancer to examine the association between the studied drugs and AKI. The use of either proton pump inhibitors or immune checkpoint inhibitors was associated with an increased risk of AKI. However, their additive interaction was not identified.

BACKGROUND

An association between proton pump inhibitor (PPI) use and an increased risk of AKI has been confirmed. This study aimed to evaluate the effects of PPI use on the risk of AKI in patients with cancer who were administered immune checkpoint inhibitors (ICIs), a class of drugs used in cancer treatment, and in those who were not.

METHODS

We used a database provided by the Health, Clinic, and Education Information Evaluation Institute, which included demographic data, diagnoses, prescriptions, and laboratory results. We conducted a nested case–control study of 38,930 patients with cancer who were new PPI or ICI users and had no history of AKI before cohort entry. The odds ratio (OR) for AKI was estimated using conditional logistic regression models.

RESULTS

During a mean follow-up of 8.3 months, 5870 cases of AKI were identified (incidence rate, 21.9/100 person-years). Compared with never or past PPI use without ICI use, the adjusted ORs of AKI for current PPI use without ICI use, past or never PPI use with prior ICI use, current PPI use with prior ICI use were 2.20 (95% confidence interval [CI], 2.01 to 2.40), 1.72 (95% CI, 1.37 to 2.17), or 2.62 (95% CI, 1.75 to 3.93), respectively. The risk of AKI in patients treated with both PPIs and ICIs was not higher than the additional or multiplication of the risks in those who were treated with PPIs or ICIs alone.

CONCLUSIONS

This study reinforces the association between PPI and ICI use and the increased risk of AKI. Although the interaction between the two drug classes was not detected, these findings highlight the need for careful monitoring and evaluation of kidney function in patients treated with PPIs and ICIs.