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

Area of Science:

• Biomedical Imaging
• Nanotechnology
• Renal Physiology

Background:

• Current clinical biomarkers for kidney disease often average whole-kidney function, missing localized or unilateral injuries.
• Early and spatially resolved assessment of renal dysfunction is crucial for effective kidney disease theranostics.

Purpose of the Study:

• To develop a contrast-sparing computed tomography (CT) approach for compartment-level mapping of renal dysfunction.
• To utilize renal-clearable glutathione-gold nanoclusters (GSH-Au NCs) for enhanced intrarenal CT contrast and early detection of kidney injury.

Main Methods:

• Developed ultrasmall (2.8 nm) glutathione-gold nanoclusters (GSH-Au NCs) with high X-ray attenuation for rapid renal clearance and intrarenal CT contrast.
• Administered low-dose GSH-Au NCs in three distinct mouse models of acute kidney injury (AKI).
• Analyzed CT imaging signatures and time-attenuation behaviors to identify mechanism-specific patterns of renal dysfunction.

Main Results:

• GSH-Au NCs provided mechanism-specific imaging signatures and distinct time-attenuation behaviors in AKI models, preceding changes in traditional biomarkers.
• Detected early bilateral cisplatin-induced kidney injury at an ultralow dose (32.5 mg Au/kg) via a bright band in the outer medulla on CT.
• Demonstrated spatial mapping of renal dysfunction consistent with tubular injury and cast/debris-mediated mechanisms.

Conclusions:

• Established a dose-efficient CT workflow for early, noninvasive, and spatial mapping of renal dysfunction.
• The GSH-Au NCs approach supports improved diagnosis, classification, and monitoring of kidney diseases.
• This method offers a significant advancement over traditional biomarkers by providing detailed, localized renal function assessment.