Monitoring kidney function might get less invasive

Our kidneys perform a lot of functions. Alongside their main job of removing waste from blood and transforming it into urine, they control the production of red blood cells, make hormones and vitamins, and regulate both blood pressure and nutrient quantities within our bodies. As a result, any disease that affects the kidneys can be life-threatening. Current methods used to monitor kidney function include blood and urine tests, which have limited sensitivity, and renal biopsies, which are invasive.

A group of Chinese researchers believe that carbon dots (CDs) that fluoresce in the near-infrared (nIR) could be a suitable, non-invasive imaging tool for the real-time analysis of kidney function. They’ve written about their research in a forthcoming issue of Carbon [DOI: 10.1016/j.carbon.2022.09.052].

CDs are a relatively new class of nanocarbons that are already attracting considerable attention in fields as diverse as anticounterfeiting and biomedicine. This is thanks to the unique combination of properties they offer – excellent (and tuneable) photoluminescence from UV to nIR, high biocompatibility, low toxicity, small size, low cost, high stability, and abundant functional groups. Previous research suggested that small-size CDs (1–6 nm) can be safely cleared via the kidneys, but as the authors of the current study wrote, despite this, “…studies have not evaluated their application to assess kidney function.”

The first challenge they faced was to develop a method for producing nIR-CDs with a reasonably high quantum yield. They did this through one-pot pyrolysis of glutathione – a carbon source – and urea – as passivator to improve luminous efficiency. The resulting nIR-CDs had three UV–Vis absorption peaks (421 nm, 641 nm, and 692 nm), exhibiting near-infrared fluorescence with a quantum yield of 14.3%, which is higher than previously reported CDs. To quantify their stability, the CDs were exposed to UV light, elevated temperatures, saline solutions and a range of pH enviroments. All tests demonstrated that the carbon dots were sufficiently stable to be used in organismal research. In in-vitro tests, the CDs showed efficient cellular uptake and good fluorescent imaging characteristics.

In-vivo tests, carried out in healthy mice, confirmed that the fluorescent CDs were stable in both blood and urine. The renal clearance efficiency was 97.47 – 99.27% after 24 hours, indicating that carbon dots injected into the body are fully metabolised within a day. This is faster than Cy5, a tracer dye commonly used in a variety of biomedical applications. The nIR-CDs were found to be non-toxic to mice too, even at elevated concentrations.

The study also confirmed that the clearance pathway of the CDs solely involves glomerular filtration – the key process your kidneys use to filter waste products. Because of this, it can be used as a measurand for renal function. To examine if the nIR-CDs could be a used as an “optical probe” for monitoring renal impairment, they injected carbon dots into a mouse model with acute kidney injury, and into a control group. They found that the fluorescence signal from the CDs increased as the degree of kidney damage increased, suggesting that nIR-CDs can be used for renal function imaging.

The authors conclude, “nIR-CDs are advantageous for the real-time monitoring of the kidney and bladder by fluorescence imaging by enabling real-time, non-invasive, and rapid detection.” They describe the carbon dots as “…a candidate nanoplatform for real-time imaging of kidney function-related disease processes. With further development, this nanoprobe may provide a promising tool for non-invasive diagnosis during disease development.”

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Pengli Gao, Hui Hui, Chanjuan Guo, Yu Liu, Ya Su, Xiazi Huang, Kunxiong Guo, Wenting Shang, Jingying Jiang, Jie Tian. “Renal clearing carbon dots-based near-infrared fluorescent super-small nanoprobe for renal imaging,” Carbon 201 (2023) 805-814. DOI: 10.1016/j.carbon.2022.09.052