NSAID-Induced acute kidney injury risk in patients on renin-angiotensin system inhibitors and diuretics: nationwide cohort study.

Background: Triple Whammy (TW) therapy, a combination of renin-angiotensin system inhibitors (RASIs), diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs), is associated with an increased risk of acute kidney injury (AKI). However, there is no consensus regarding the impact of NSAID type on the risk of AKI. Therefore, in this study, we evaluated the incidence and risk of NSAID-induced AKI in patients taking concomitant RASIs and diuretics, focusing on NSAID type.

Methods: We conducted an observational retrospective cohort study using a Japanese medical claims database. In the cohort analysis, 41,904 patients who received concomitant RASIs, diuretics, and newly added NSAIDs between April 2020 and March 2021 were included to estimate AKI incidence. In the case-crossover analysis, 2,909 patients who developed AKI while on RASIs and diuretics were analyzed to assess the short-term risk associated with NSAID use. Incidence rates were calculated using the person-year method. Conditional logistic regression was used to estimate adjusted odds ratios (aOR), accounting for surgical procedures and concomitant AKI risk drugs.

Results: Among 41,904 patients, 54 developed AKI (20.0 [95% CI: 14.8-25.6] per 1,000 person-years). The incidence rate ratio of TW to RASIs and diuretics without NSAIDs was 2.08 [95% CI: 1.58-2.74]. Case-crossover analysis showed an aOR of 1.44 [95% CI: 1.17-1.78] for AKI associated with NSAID use. No substantial differences were observed between COX-2 selective and nonselective NSAIDs (aOR: 0.99 [95% CI: 0.66-1.50]).

Conclusions: The addition of NSAIDs to RASIs and diuretics significantly increased AKI risk, emphasizing the need for careful monitoring regardless of the NSAID type.