Single-cell analysis to promote kidney repair

Key Personnel

Project Description

Acute kidney injury (AKI) has a wide spectrum of outcomes from recovery to a long-term transition to chronic kidney disease (CKD). Between 2000 and 2014, AKI hospitalizations have increased from 3.5 to 11.7 per 1000 persons. Medicare patients aged 66 years and older hospitalized for AKI have a 35% cumulative probability of a recurrent AKI hospitalization within one year and 28% will be diagnosed with CKD in the same time frame. Men have a higher risk of AKI, and of developing progressive CKD, although the mechanisms are poorly understood. In the mouse, males also show a heightened vulnerability to AKI. Recent single cell RNA-seq studies have highlighted marked differences in gene expression between the sexes in proximal tubule segments, the region of the nephron most susceptible to AKI. Other work has identified a cell type resulting from failed repair of proximal tubule cells (FR-PTC) following mild to severe AKI with a pro-inflammatory, pro-fibrotic signature. FR-PTCs are hypothesized to drive progressive kidney disease following AKI. This proposal centers on the postulates that an understanding of sex differences in response to AKI, and the application of genetic approaches to target proinflammatory properties of FR-PTCs and to eliminate FR-PTCs following renal repair, will be effective routes to ultimately benefit patient outcomes post AKI.