Fluorescently Labeled Cyclodextrin Derivatives as Exogenous Markers for Real-Time Transcutaneous Measurement of Renal Function

Abstract

Evaluation of renal function is crucial for a number of clinical situations. Here, we reported a novel exogenous fluorescent marker (FITC-HPβCD) to real-time assess renal function by using a transcutaneous fluorescent detection technique. FITC-HPβCD was designed based on the principle of renal clearance of designed drugs. It displays favorable fluorescent properties, high hydrophilicity, low plasma protein binding, and high stability in porcine liver esterase as well as in plasma and nontoxicity. More importantly, FITC-HPβCD can be efficiently and rapidly filtered by glomerulus and completely excreted into urine without proximal tubular reabsorption or secretion in rat models. Additionally, the marker was well-tolerated, with nearly 100% urinary recovery of the given doses, and no metabolism were found. Relying on this novel kidney function marker and transcutaneous devices, we demonstrate a rapid, robust, and convenient approach for real-time assessing renal function without the need of time-consuming blood and urine sample preparation. Our work provides a promising tool for noninvasive real-time monitoring of renal function in vivo.

Light‐Emitting Agents for Noninvasive Assessment of Kidney Function

“…The functional state of the kidneys can be assessed by using the glomerular filtration rate (GFR), renal blood flow, and tubular reabsorption or secretion of various substances . Among them, the GFR is often used to evaluate overall renal function and is accepted as the best indicator for kidney function . The GFR represents the plasma volume cleared by the nephrons per time unit during urine formation.…”

“…The concentration of endogenous creatinine in plasma is commonly used to determine the GFR (Figure b), but it may result in erroneous estimates due to age, gender, muscle mass, and many other anthropometric variables . Determination of the plasma/urinary clearance of exogenous renal agents such as 99m Tc–DTPA (diethylenetriaminepentaacetic acid, DTPA), inulin, and iothalamate (Figure c) is invasive and cumbersome due to the requirement of multiple blood/urine sampling steps and tedious sample analysis by high‐performance liquid chromatography (HPLC) . Moreover, many studies have revealed that creatinine and iothalamate are secreted by proximal tubule cells, whereas cystatin C and 99m Tc–DTPA are reabsorbed by the tubular epithelial cells, which leads to a bias in the GFR .…”

“…It is necessary to take all of these characteristics into account for the rational design of a GFR agent. Bearing this in mind, we have successfully developed 2‐hydroxypropylcyclodextrin (HPCD)‐based fluorescent agents for the transcutaneous measurement of kidney function . Fluorescent HPCD‐based agents are judiciously designed by combining the basic principle of renally cleared drugs and the knowledge of a cyclodextrin (CD)‐based drug‐delivery system.…”

“…b) Structures of endogenous renal function markers. c) Structures of exogenous renal function markers . Reprinted with permission from Ref.…”

“…Finally,w ed iscussf uture challenges in expediting clinical translation of these developed light-emitting agents, along with considerations of the efforts that need to be made to develop new agents and diagnosing kidney disease. [8] Reprintedw ith permissionf rom Ref. [8].C opyright( 2016) American Chemical Society.…”