Dissecting the heterogeneity of acute kidney injury in critical care

Dissecting the heterogeneity of acute kidney injury in critical care

Acute kidney injury (AKI) is a rapid decline in renal function caused by inflammatory, ischemic, or nephrotoxic insults, often triggered by sepsis, trauma, or complex surgery. Affecting up to 60% of ICU patients, AKI is associated with high morbidity, mortality, and long-term kidney dysfunction. Despite advances in supportive care, early diagnosis and effective treatment remain limited due to the heterogeneity of AKI in terms of etiology and clinical presentation.

This thesis of Daniela Jou-Valencia aims to improve early AKI detection and classification by identifying renal biomarkers and clinical variables in critically ill patients. It integrates plasma biomarker profiling and clinical data in a general ICU cohort with renal tissue analysis from patients with sepsis- and COVID-19-associated AKI. The role of Klotho is further explored through translational studies in murine endotoxemia models and human sepsis-related AKI.

Findings reveal that biomarker expression varies across AKI etiologies and timepoints, limiting their stand-alone diagnostic utility. Even within a single etiology such as sepsis, distinct biomarker patterns suggest the presence of sepsis-AKI subtypes. COVID-19-related AKI displays unique features, including microvascular thrombosis and endothelial dysfunction, consistent with ischemic injury. My mechanistical work on Klotho shows protective effects against renal damage, inflammation, and endothelial activation.

This work highlights the need for a biomarker-informed AKI classification by integrating clinical, histopathological, and molecular data. It contributes to the development of patient-specific diagnostics and therapies for AKI in critically ill patients.

Dissertation: https://hdl.handle.net/11370/0ac82be3-b7d9-4804-a283-1d36275c44f2