Early Detection and Noninvasive Staging of Kidney Dysfunction by a PEGylated Conventional Fluorophore via GFR-Sensitive Renal Transport.

Abstract

Noninvasive fluorescence imaging of renal function is a valuable technique for understanding kidney disease progression and the development of renal medicine. This technique requires sensitive imaging probes for reporting renal dysfunction accurately at early stage. Herein, a molecularly engineered imaging probe (800CW-PEG45-COOH) was synthesized by simply PEGylating conventional near-infrared fluorophore IRDye800CW with NH2-PEG45-COOH (molecular weight ∼2100 Da) for early detection and staging of renal dysfunction through noninvasive real-time kidney imaging. 800CW-PEG45-COOH not only cleared through the kidney efficiently (>90% injection dosage at 24 h postinjection) but was also found to be freely filtered by glomeruli without renal tubular reabsorption and secretion. Despite this simple construction strategy, the transport of 800CW-PEG45-COOH within the kidneys was extremely sensitive to the alteration of the glomerular filtration rate (GFR), which enabled it to detect renal dysfunction much earlier than commonly used serum biomarkers and stage kidney function impairments (mild vs severe dysfunction) via imaging-based kidney clearance kinetics. This work not only provides a promising optical imaging probe for the noninvasive evaluation of kidney function but also highlights the utility of PEGylation in enhancing the performance of conventional organic dyes in biomedical applications.