Costa, Filipa da Palma Carlos Alves daFernandez-Llimos, FernandoDuarte-Ramos, FilipaOliveira, Catarina Da Luz2025-07-302025-052025-03http://hdl.handle.net/10400.5/102565The thesis focuses on identifying the determinants and consequences of drug-induced acute kidney injury (AKI), investigating risk factors to enhance prevention strategies. Chapter 1 introduces the topic of AKI, providing a definition of the concept, its epidemiological context and summarising the evidence of its risk factors, diagnostic approaches and impact on the health system and the individuals' health and well-being. The main objective of the thesis (Chapter 2) was to contribute to the existing knowledge on the impacts of AKI on health and thus lead to formulate a hypothesis that an important proportion of medication-induced AKI cases occurring in hospitalized patients may be prevented by clinical pharmacy interventions. This thesis is structured into five chapters. We first take a health-system approach to understand why systems fail in preventing AKI (Chapter 3), we then focus on the individuals (Chapter 4), by exploring pharmacovigilance reports, and finalise by analysing the role of the clinical pharmacist in preventing AKI (Chapter 5), inferring on the extent to which international good practice examples could be adapted to the national context. In Chapter 3, we evaluated the real-world impact of hospital practices related to serum creatinine (SCr) testing on the identification and classification of AKI and its implications for drug dose adjustments. A historical cohort study was conducted using clinical records of all adult patients over a two-and-a-half-year period in a public general hospital serving the Tejo Estuary region, integrated into Portugal's National Health Service. The Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) criteria were applied to determine AKI, considering the time intervals between two SCr tests as outlined by these criteria. Additionally, patients with SCr increases exceeding AKI limits, regardless of the time interval, were also identified. Estimated glomerular filtration rate (eGFR) and kinetic eGFR (KeGFR) were calculated, and medications requiring dose adjustment were identified. Any stage of AKI was identified in 7.0% of patients using AKIN criteria and in 9.1% using KDIGO criteria. Ignoring time limits for both criteria revealed AKI in 1,942 patients (11.2%), suggesting a potential underdiagnosis of AKI by 37.5% or 19.1%, depending on the criterion used. A total of 76 medications requiring dose adjustments in patients with eGFR ≤50 mL/min were prescribed in 78.5% of hospitalizations. These medications were prescribed in 87.9% of patients potentially underdiagnosed by AKIN criteria and in 88.9% considering KDIGO criteria. To identify the medications most frequently reported as AKI inducers, we conducted a case/non case study based on the Portuguese National Pharmacovigilance Database (Chapter 4). Over an 11-year period, we identified the effects of specific therapeutic classes and individual medications. Significant disproportionality was observed in three therapeutic subgroups: antithrombotic, antiviral, and antineoplastic agents. Eleven medications were identified as potentially associated with AKI, some well documented and others requiring further investigation. Disproportionality analysis suggested an association between AKI and dabigatran etexilate, simvastatin, emtricitabine, and mycophenolic acid. Chapter 5 discusses the results of the previous chapters, highlighting the strenghts of the work conducted while acknowledging the limitations of the conducted studies. Overall, this project underscored the necessity of modifying hospital protocols to increase the frequency of SCr testing. Early identification of patients who could benefit from pharmaceutical intervention was emphasized. The project also underlined the importance of spontaneous reporting of adverse drug reactions (ADRs), allowing the identification of some medications requiring additional investigation to validate their association with AKI. This study underscores the risks associated with certain drugs, emphasizing that these risks may be influenced by existing healthcare practices. As the healthcare professional responsible for pharmaceutical validation, the clinical pharmacist can play a pivotal part in the systematic monitoring of renal function, particularly in patients with known risk factors or those receiving medications associated with an increased risck of AKI. To ensure timely monitoring and appropriate therapeutic adjustments, organizational changes would be required, aligning with international best practices where pharmacists are authorized to request laboratory tests and adjust medication dosages as needed. Implementing these measures could significantly enhance the early detection of AKI and support preventive strategies, such as minimizing the use of medications with the potential to cause AKI or nephrotoxicity in at-risk populations.engLesão Renal AgudaServiço de Farmácia HospitalarFarmacovigilânciaFarmácia ClínicaGestão do RiscoAcute Kidney InjuryPharmacy ServiceHospitalPharmacovigilanceClinical PharmacyRisk Managementdoctoral thesis101735219