Disproportionality Analysis of Acute Kidney Injury Reports Associated with Sacubitril/Valsartan (ARNI) in the Japanese Adverse Drug Event Report Database

Abstract

BACKGROUND: Prescriptions of angiotensin receptor neprilysin inhibitor (ARNI) have increased in recent years; however, few pharmacovigilance studies have investigated acute kidney injury (AKI) reporting associated with ARNI. This study evaluated the disproportionate AKI reporting associated with ARNI in the Japanese Adverse Drug Event Report (JADER) database, compared AKI reporting between reports involving ARNI and valsartan, and explored the factors associated with AKI reporting among reports involving ARNI. METHODS: Reports published in JADER between April 2020 and August 2023 were analyzed. AKI was identified using the narrow and broad scope Preferred Terms of the Standardized MedDRA Query (SMQ) "acute renal failure" (SMQ:20000003). The reporting odds ratios (RORs) and 95% confidence intervals (CIs) were calculated for ARNI and valsartan. Multivariable logistic regression analyses were performed to estimate adjusted RORs (aRORs) for sex, age, heart failure (HF), diabetes mellitus, chronic kidney disease (CKD), concomitant diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs). An additional adjusted analysis directly compared AKI reports between ARNI and valsartan. RESULTS: A disproportionality signal for AKI was identified in the reports involving ARNI (ROR 7.11, 95% CI 6.27-8.07). Multivariable logistic regression showed that HF (aROR 1.68, 95% CI 1.22-2.31; p = 0.002) and CKD (aROR 2.17, 95% CI 1.60-2.93; p < 0.001) were independently associated with increased AKI reporting among reports involving ARNI. In the adjusted direct comparison, reports involving ARNI had higher odds of AKI reporting than those involving valsartan (aROR 2.03, 95% CI 1.50-2.74). CONCLUSIONS: Disproportionate AKI reporting signals were identified in reports involving ARNI in the JADER database. HF and CKD were independently associated with increased AKI reporting after adjustment. These findings have provided additional pharmacovigilance evidence regarding ARNI-associated AKI in Japan and should be interpreted in light of the inherent limitations of spontaneous reporting data.

The authors' abstract, as published at the source. Drugs - Real World Outcomes, 2026 · DOI ↗