Angiotensin receptor-neprilysin inhibitor and sodium-dependent glucose cotransporter-2 inhibitor-associated renal injury: a pharmacovigilance study

ABSTRACT

Background

Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-dependent glucose cotransporter-2 inhibitors (SGLT-2Is) had a certain risk of renal injury. However, overlapping nephrotoxicity of combination therapy was unclear.

Research design and methods

We performed a disproportionality analysis based on the Food and Drug Administration Adverse Event Reporting System from 1 January 2004 to 31 December 2020. Renal injury cases were defined as acute kidney injury (AKI) and chronic kidney disease (CKD) cases.

Results

We detected a significant association between ARNI, SGLT-2Is, the combination therapy and AKI as well as CKD, in which the combination therapy generated the highest strength association with both AKI (ROR: 8.06, 95% CI 5.41–12.01) and CKD (ROR: 2.69, 95% CI 1.27–5.71). Compared with ARNI or SGLT-2I alone, the combination therapy generated AKI signals. There were no differences in the onset time of renal injury cases between the combination therapy and monotherapy. Compared to cases without renal injury, the combination therapy did not increase the proportion of fatality and hospitalizations in cases with AKI or CKD.

Conclusion

The combination of ARNI and SGLT-2Is was associated with a significantly increased reporting proportion of AKI. However, due to the limitations of the FAERS database, our results required further studies to assess our findings.

KEYWORDS:

• Acute kidney injury
• Chronic kidney disease
• Angiotensin receptor-neprilysin inhibitor
• Sodium-glucose cotransporter-2 inhibitors
• Pharmacovigilance

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer is a consultant for Lexicon (sotagliflozin), Bayer, astra zeneca, Boehringer ingelheim/Lilly (empagliflozin), Merck. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Author contributions

C Chen: designed the work, analyzed the data, and drafted the article. B Win and T Xu designed the work, acquired and analyzed the data, and corrected the manuscript. CY Zhang participated in the study design and plotted figures.

Data availability statement

The FAERS datasets are available to the public online: https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-latest-quarterly data-files. The data that support the findings of this study are available from the corresponding author, [BW], upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2022.2120609

Additional information

Funding

This study is supported by the National Key Research and Development Program of China (NO:2020YFC2008302).