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

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.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.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.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.