Development of a new diagnostic method to increase the success rate of brain-dead kidney transplants

Aug 06, 2024

Development of a new diagnostic method to increase the success rate of brain-dead kidney transplants
A schematic diagram of kidney injury diagnosis using a fluorescent molecular probe that detects cysteine levels.
Korean researchers have developed a method to quickly and accurately diagnose ischemic kidney damage (lack of blood flow in the kidneys) in brain-dead donor kidneys. This method is expected to contribute to securing implantable kidneys and increasing the success rate of kidney transplantation.

A joint research team led by Professor Min Sang-il of transplantation vascular surgery at Seoul National University Hospital and Professor Kim Do-kyung of Kyung Hee University Medical School announced on the 6th a method to diagnose ischemic kidney damage using a fluorescent molecular probe (NPO) that identifies an increase in amino acids called cysteine. Cysteine is known to increase its level when kidney damage occurs.

Kidney transplantation is a treatment method that provides better survival and cost-effectiveness than dialysis for patients with end-stage renal disease. However, brain-dead donor kidneys are at high risk of ischemic kidney injury, so it is important to quickly and accurately diagnose the extent of injury before transplantation. Existing renal function evaluation biomarkers were limited because they lacked sensitivity and specificity in diagnosing acute renal injury, and there was no clear correlation with histological injury severity.

To address this issue, the research team used a fluorescent molecular probe called NPO to diagnose kidney injury. This probe reacts with cysteine to give off fluorescence, allowing the detection of an increase in cysteine in the damaged kidney. Experiments using human kidney cells confirmed a significant increase in cysteine levels under hypoxic conditions.

In animal model experiments, the kidneys of normal and ischemic-injured mice were compared and analyzed using an NPO probe in an ischemic-reperfusion-injured model with mice. As a result, the NPO fluorescence intensity in the kidneys of ischemic-injured mice was much stronger than that of normal mice. This means that NPO can effectively diagnose and visualize the severity of kidney injury.

Finally, the research team collected urine samples from brain-dead donors and living donors and compared and analyzed the fluorescence intensity using NPO. As a result, the NPO fluorescence intensity in the urine of brain-dead donors was much stronger than that of the living donor. This means that the kidneys of brain-dead donors are more severely damaged, demonstrating that NPOs can effectively identify high-risk groups for kidney injury.

Professor Kim Do-kyung (Department of Medicine at Kyung Hee University) said "This study shows that NPO probes can be used to accurately diagnose kidney damage" This suggests that existing biomarkers can overcome their limitations, and we hope that fluorescent molecular probes can be widely used in diagnosing various diseases in the future."

Professor Sang-il Min (SNU Hospital Transplant Vascular Surgery) said "NPO probes can be easily used in clinical practice as they can assess kidney injury with simple urine sample analysis."By accurately diagnosing kidney damage in brain-dead donors in advance, we hope that we can effectively secure transplantable kidneys to help improve the prognosis of recipients after transplantation, and reduce the proportion of donor kidneys that are discarded even though they are available."," he added.

This study was conducted with the support of the Ministry of Science and ICT's Korea Health Technology Research and Development Project, and was published in the recent issue of the World Transplantation (IF=5.3), an official international academic journal of the World Transplantation Society.



Development of a new diagnostic method to increase the success rate of brain-dead kidney transplants
Professor Min Sang-il of transplant vascular surgery at Seoul National University Hospital (left) and Professor Kim Do-kyung of Kyung Hee University Medical School


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