Precision Medicine for Acute Kidney Injury (AKI): Redefining AKI by Agnostic Kidney Tissue Interrogation and Genetics

摘要

Acute kidney injury (AKI) is currently diagnosed by a temporal trend of a single blood analyte, the serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lcn2, Siderocalin) or kidney injury molecule-1 (KIM-1, HAVCR1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine elevation. Nonetheless, these biomarkers lack the capacity to further sub-fractionate AKI (e.g. sepsis vs ischemia vs nephrotoxicity from medications, enzymes or metals) or inform us about the primary and the secondary sites of injury. It is also unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single cell and single nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification and staging, and provide the renal community with a significant advance towards precision medicine in the analysis AKI.