Clinical Roles for Biomarkers Of Sepsis - Associated Acute Kidney Injury

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Acute kidney injury (AKI) is defined as an abrupt decrease of the glomerular filtration caused by different etiologies and is classified according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine (sCr) and urine output (UO). Acute kidney injury is one of the possible organ dysfunctions that could be present in sepsis (and also being one of its determinants). Sepsis is the most common cause of AKI and AKI affects almost half of patients admitted to intensive care units. AKI is also an important risk factor for sepsis and the presence of sepsis-associated acute kidney injury (SA-AKI) strongly impact patients’ outcomes. Early detection of AKI in sepsis is crucial for getting optimal treatment and avoiding further kidney injury. In addition, the early detection of AKI in the setting of infection plays a crucial role since it may define sepsis itself. Combining markers of kidney stress or injury together with markers of function (e.g., sCr and UO) may provide clinicians more information than either alone. Several markers have been studied in SA-AKI, in particular urinary kidney injury molecule-1 (KIM-1) and urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) together with insulin-like growth factor-binding protein 7 (IGFBP7). In addition, the soluble form of the tyrosine kinase receptor Mer (sMer) and its ligand growth arrest-specific 6 protein (Gas6) since they have pleiotropic effects related to the immune system regulation and inflammation/sepsis as well. In this thesis we reported the results of five scientific articles exploring different potential clinical roles for biomarkers of SA-AKI. We showed their prognostic role, that they can help with AKI staging and stratification, and that they may even guide the application of treatment strategies.