Background and Importance Acute kidney injury (AKI) is a highly prevalent condition among inpatients, usually attributed to pharmacological causes. One of the most clinically relevant drug-drug interactions (DDI) in this context is the triple whammy interaction (TWI), caused by the addition of three potential nephrotoxic groups of drugs: Non-steroidal anti-inflammatory drugs (NSAIDs), diuretics and ACE inhibitors/angiotensin receptor blockers (ARB).

Aim and Objectives To evaluate clinical significance of the TWI, as well as the role of pharmaceutical intervention (PI) in preventing possible adverse events due to this DDI.

Material and Methods Observational retrospective study that included patients who were prescribed the TWI over a period of 4 years (2018 to 2022). Data were collected using computerised medical records, nurse administration registry and PI data base. ICU patients were excluded from this study. Recommendation of monitoring serum creatinine and potassium, as well as discontinuing the triple therapy was carried out in all patients. Incidence of AKI was calculated according to AKIN criteria. Impact of PI was estimated based on average number of days patients received the combination and amount of time until complete resolution of AKI.

Results 34 patients were included and stratified according to their risk factors for developing AKI. 87,5% patients were considered at high risk. The first cause of admission was surgery in 62% of cases. Mean basal SCr was 0,99 (CI 95% 0,82–1,15). Acceptance of PI rate was estimated in 65,62%. Incidence of AKI was 29,4% (10/34), 8 of which were classified as AKIN 1. Mean duration of the triple therapy was 6,81 days (CI 95% = 3,47-10,15) in non-accepted PI group vs 3,17 days (CI 95% = 2,23-4,11) in the accepted PI group. AKI was detected more frequently in accepted PI patients (7/10). However, these patients recovered normal renal function faster than patients with no approved PI: 10 days (CI 95% = 5,41-14,58) vs 14,33 days (CI 95% = 8,52 – 20,14), respectively.

Conclusion and Relevance The TWI can participate in acute kidney injury, particularly in high risk patients. Clinical pharmacists play an important role detecting patients at increased risk of AKI, preventing adverse events due to TW interaction, monitoring AKI biomarkers and recommending deprescription of possible nephrotoxic drugs.

Conflict of Interest No conflict of interest