Scientists develop probes to detect early acute kidney failure

Scientists at Singapore's Nanyang Technological University (NTU Singapore) have developed a type of imaging probe that can detect early acute kidney failure, a rapidly developing disease that can be fatal.

The new kidney probes, which have been tested in mice, are injected into the blood. They "light up" when they detect molecular changes caused by the onset of acute renal failure.

Developed by Associate Professor Pu Kanyi and his team at NTU Singapore, these probes could eventually be used in test strips for urine samples, making it a non-invasive method of detecting acute kidney failure.

Acute kidney failure usually occurs within hours or days. It is more common in critically ill patients requiring intensive care. Current diagnostic platforms are unable to detect the early-stage early changes that are at the root of acute renal failure.

In contrast, the molecular imaging probe developed by the NTU team is sensitive enough to track changes in biological processes triggered by the onset of the disease.

When tested on mouse models with drug-induced acute renal failure, the NTU-developed molecular renal probes detected the onset of the disease 1.5 days earlier than current molecular imaging procedures. . The results were published in Nature's materials in May.

Associate Professor Pu Kanyi, NTU's School of Chemical and Biomedical Engineering, said: "For critically ill patients, such as those in the intensive care unit, every minute is precious to remedy a problem like acute renal failure, Molecular renal probes are useful because they track the subtle changes of the body at the molecular level and could help stop the development of the disease before it's too late – this which is impossible with the current diagnostic methods do. "

Assoc Prof Pu is considering the use of these probes in an intensive care unit, where early detection of acute renal failure is paramount for patient survival.

"In our next phase of research, we need to focus on probing probes with urine samples of critically ill patients, and we plan to do this by collaborating with medical institutions both in Singapore and at the same time. 39; abroad. "

The team has filed a patent in Singapore on this technology.

How it works

To ensure that molecular renal probes follow appropriate biological signals and processes, Professor Assoc, M. Pu, and his team first identified reactive oxygen species (ROS). ), chemically unstable molecules serving as early biomarkers for kidney damage. An imbalance of the ROS in the body causes lesions of adipose tissue, DNA and proteins of the body. Doctors know that it can trigger cell death pathways in an organ and kidney fibrosis, in which a damaged kidney can no longer heal.

Assoc Prof Pu said: "Many reports have shown that ROS-induced byproducts are dysregulated in plasma or urine before an acute kidney injury occurs.This implies that a direct detection ROS could help identify acute renal failure earlier. "

The team then created probes composed of three components: a part that reacts with the identified ROS; a luminescence signaling portion which ensures that the probe turns on during this reaction; and a part that ensures the probe pbades through the kidneys instead of accumulating in the liver (see chart below). These probes are sensitive enough to detect subtle changes in biomarker concentrations, thus enabling early detection of the disease.

The probes were injected into mice after administering cisplatin, an anticancer drug, at a destructive level for the kidneys. Twelve hours after cisplatin injection, the probe lit up, signaling the detection of a change in biomarkers related to acute kidney injury. This is consistent with the renal tubular lesions measured in mice three days after the administration of cisplatin.

In addition to testing the probe's ability to detect signs of acute renal failure, the NTU team also found that the probe had high renal clearance: over 97% of the probes injected into mice were pbading by the kidneys and were excreted in the urine.

The high efficiency of the renal clearance of the probe means that these probes could be used directly on urine samples, said Assoc Prof Pu. When they are added to the urine sample and incubated for a few hours, the probes light up when they are exposed to ultraviolet light in the presence of biomarkers. This opens the possibility of developing these probes in the form of test strips for urine samples, making it a potential noninvasive method of controlling acute renal failure in the future. he declared.