Contrast-sparing CT using renal-clearable gold nanoclusters for early spatial mapping of renal dysfunction

Early, noninvasive, and spatially resolved assessment of renal dysfunction is essential for theranostics of kidney diseases, yet clinical biomarkers are criticized for averaging whole-kidney function and missing focal or unilateral injury. Here, we present a contrast-sparing computed tomography (CT) approach that maps renal dysfunction at the compartment level using renal-clearable glutathione-gold nanoclusters (GSH-Au NCs). The merits of ultrasmall hydrodynamic size (2.8 nanometers) and high x-ray attenuation ability enable GSH-Au NCs with fast renal clearance and robust intrarenal CT contrast. In three mechanistically distinct mouse models of acute kidney injury, low-dose GSH-Au NCs produced mechanism-specific imaging signatures and distinct time-attenuation behaviors, even before biomarkers changed. Notably, at an ultralow dose (32.5 milligrams of Au per kilogram), early bilateral cisplatin injury can be easily detected with an obvious bright band at the outer medulla area on CT, consistent with tubular injury and a cast/debris-mediated mechanism. This work establishes a dose-efficient CT workflow for early, noninvasive, spatial mapping of renal dysfunction, supporting diagnosis, classification, and monitoring of kidney disease.