Effect of "triple whammy" combination in hospitalization due to acute kidney injury: a protocol of a nested casecontrol study

Abstract Objective: Acute kidney injury (AKI) is a life-threatening condition characterized by an abrupt deterioration in kidney function. The simultaneous use of diuretics, renin-angiotensin-aldosterone system inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs) or metamizol, known as "triple whammy" (TW), has been associated with an increased risk of AKI. The main objective of the study is to analyse the risk of hospitalization due to AKI with the TW combination versus non-exposure to TW. Additionally, hospitalization due to AKI according to the time and duration of the TW exposure, and depending on whether the TW includes NSAIDs or metamizol; mortality; and the requirement of renal replacement therapy will be determined. Methods: A case-control study nested in a cohort will be carried out. Data for the study will be extracted from the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP), managed by the Spanish Agency for Medicines and Medicine and Health Products (AEMPS). Adults admitted to hospital due to AKI between 2010 and 2018 (cases) will be matched with up to 10 controls per case. The exposure to TW during the 12 months prior to the index date will be determined. The association between the exposure to TW and the outcomes will be analysed using multivariate logistic regression models adjusting by potential confounding factors. A subgroup analysis will be performed to evaluate the risk of hospitalization due to AKI with the exposure to TW in patients older than 75 years.