Abstract
Renal function biomarkers such as serum blood urea nitrogen (BUN) and creatinine (Cr) serve as key indicators for guiding clinical decisions before administering kidney-excreted small-molecule agents. With engineered nanoparticles increasingly designed to be renally clearable to expedite their clinical translation, understanding the relationship between renal function biomarkers and nanoparticle transport in diseased kidneys becomes crucial to their biosafety in future clinical applications. In this study, renal-clearable gold nanoparticles (AuNPs) are used as X-ray contrast agents to noninvasively track their transport and retention in cisplatin-injured kidneys with varying BUN and Cr levels. The findings reveal that AuNP transport is significantly slowed in the medulla of severely injured kidneys, with BUN and Cr levels elevated to 10 times normal. In mildly injured kidneys, where BUN and Cr levels only four to five times higher than normal, AuNP transport and retention are not predictable by BUN and Cr levels but correlate strongly with the degree of tubular injury due to the formation of gold-protein casts in the Henle's loop of the medulla. These results underscore the need for caution when employing renal-clearable nanomedicines in compromised kidneys and highlight the potential of renal-clearable AuNPs as X-ray probes for assessing kidney injuries noninvasively.