Acute kidney injury biomarkers in the single-cell transcriptomic era

Acute kidney injury (AKI) affects many hospitalized patients and is associated with increased morbidity and mortality even at milder and reversible stages. The current clinical definition relies on serum creatinine increases or decreased urinary output. However, both parameters are of limited use because of poor sensitivity, specificity, and timeliness. Furthermore, the complex pathophysiology and diverse etiologies underlying AKI confound these issues. Precise biomarkers for specific aspects of AKI are needed. Earlier AKI biomarkers were unsuccessful in addressing these needs because they either lacked sensitivity and specificity or failed to aid in guiding clinical management. The advent of single-cell transcriptomics technologies provides an unprecedented opportunity to analyze cells from urine, blood, or kidney biopsies to elucidate the detailed, cell-specific, molecular responses in AKI. These technologies uncover the cellular sources of traditional biomarkers, capture patient heterogeneity, define cell states associated with different AKI subtypes, and might eventually help to predict therapeutic response. We discuss how single-cell technologies might transform diagnostic approaches to AKI by moving from single biomarkers to cell-specific molecular signatures.