Spectroscopy Method Could Raise Number of Viable Donor Kidneys

Researchers at the University of Shanghai for Science and Technology and the Changhai Hospital of Shanghai used label-free surface-enhanced Raman scattering (SERS) spectroscopy to quantitatively assess donor kidney quality, reportedly for the first time. The researchers used highly sensitive spectroscopic analysis to simultaneously detect two biomarkers for kidney injury: secretory leukocyte peptidase inhibitor (SLPI) and interleukin 18 (IL-18).

According to the team, the method provided a combined assessment of SLPI and IL-18 expression that was fast and replicable.

SERS spectroscopy uses nanostructures to enhance the Raman scattering that occurs when molecules are adsorbed onto a metal surface. This scattering forms a different spectral fingerprint for each molecule. To improve the sensitivity, reproducibility, and simplicity of SERS for clinical use, the researchers developed a hybrid SERS substrate that combined gold (Au) nanoparticles with black phosphorus (BP), a 2D nanomaterial. They attached the Au nanoparticles to the surface of BP nanosheets, creating BP/Au nanohybrid substrates for the detection SLPI and IL-18 in buffered solution and blood serum.

The BP/Au nanohybrids demonstrated strong affinity toward biomolecules, which boosted their sensitivity to the target biomarkers. The nanohybrid substrates also eliminated the need for labels, making measurements easier to perform.

Characterization of the SERS signals of the SLPI and IL-18 biomarkers enabled the researchers to quantitatively detect each biomarker. Tests using the hybrid SERS substrate showed a reproducible detection limit down to 1.53 × 10⁻⁸ mg per mL for SLPI and 0.23 × 10⁻⁸ mg per mL for IL-18. The limits of quantification were 5.10 × 10⁻⁸ mg per mL and 7.67 × 10⁻⁹ mg per mL for SLPI and IL-18, respectively.

The highly sensitive SERS-based technique can detect the biomarkers with a concentration down to 0.02 ng per mL, which is much lower than the expression level in donors without acute kidney injury. The researchers demonstrated simultaneous assessment of SLPI and IL-18, showing that the SERS technique can be used to identify and classify multiple targets in a single assay. The analysis process using the SERS spectroscopy technique is simple and time-saving, the researchers said.

Researchers have developed a new SERS method to detect biomarkers related to kidney injury in blood serum or urine. The highly sensitive approach could one day offer a more accurate way to evaluate the quality of kidneys before transplantation. Courtesy of Hui Chen, University of Shanghai for Science and Technology, and Mingxing Sui, Changhai Hospital of Shanghai.

When someone bequeaths a kidney, a biopsy is frequently taken to evaluate the health of the organ; this step is invasive and time-consuming, and it can disqualify many viable, much-needed donor kidneys. According to the Shanghai team, previous research has shown that biopsy findings don’t always predict how well a kidney will function once transplanted.

“Today, the lack of methods for precisely measuring donor kidney injury and predicting transplant outcome leads to high discard rates and recipient complications in clinical practice,” team leader Mingxing Sui from Changhai Hospital said. “We want to solve this problem by developing a new system that can noninvasively provide an objective measure of donor kidney quality.”

The new technique could be a valuable tool for clinicians to check donor kidney quality prior to transplantation, and it could also be useful for diagnosing kidney problems in patients.

“This highly sensitive SERS-based multiplexing technique can rapidly capture subtle changes in the biomarker expression levels associated with donor kidney injury,” Sui said. “This paves the way for objectively assessing the quality of donor kidneys in clinical practice.”

The researchers are working to identify additional biomarkers that could help assess donor kidney quality. They are also developing machine learning algorithms to improve the interpretation of the SERS spectral fingerprints.

“Although this work is still at an early stage, we think SERS could be used in clinical practice in the foreseeable future,” Sui said. “By collecting the donor urine or serum, the expression level of kidney injury biomarkers could be noninvasively, rapidly, and reproducibly measured, which is highly preferable in clinical practice in contrast to biopsies of kidneys.”

The research was published in Optics Express (www.doi.org/10.1364/OE.445809).