The first device to monitor transplanted organs senses warning signs three weeks earlier than current methods
Northwestern University researchers have developed the first electronic device for continuously monitoring the health of transplanted organs in real time.
Sitting directly on a transplanted kidney, the ultrathin, soft implant can detect temperature irregularities associated with inflammation and other body responses that arise with transplant rejection.
It then alerts the patient or physician by wirelessly streaming data to a nearby smartphone or tablet.
In a new study, the researchers tested the device on a small animal model with transplanted kidneys and found the device detected warning signs of rejection up to three weeks earlier than current monitoring methods.
This extra time could enable physicians to intervene sooner, improving patient outcomes and wellbeing as well as increasing the odds of preserving donated organs, which are increasingly precious due to rising demand amid an organ-shortage crisis.
Rejection can occur at any time after a transplant – immediately after the transplant or years down the road.
It is often silent, and patients might not experience symptoms, the study authors said.
Dr Lorenzo Gallon, a Northwestern Medicine transplant nephrologist, who led the clinical portion of the study, said: “I have noticed many of my patients feel constant anxiety – not knowing if their body is rejecting their transplanted organ or not.
“They may have waited years for a transplant and then finally received one from a loved one or deceased donor. Then, they spend the rest of their lives worrying about the health of that organ.
“Our new device could offer some protection, and continuous monitoring could provide reassurance and peace of mind.”
Device development
Northwestern’s John A Rogers, a bioelectronics pioneer who led the device development, said it’s critical to identify rejection events as soon as they occur: “If rejection is detected early, physicians can deliver anti-rejection therapies to improve the patient’s health and prevent them from losing the donated organ.
“In worst-case scenarios, if rejection is ignored, it could be life threatening. The earlier you can catch rejection and engage therapies, the better. We developed this device with that in mind.”
Surabhi Madhvapathy, a postdoctoral researcher in Rogers’ laboratory and the paper’s first author, said: “Each individual responds to anti-rejection therapy differently.
“Real-time monitoring of the health of the patient’s transplanted organ is a critical step toward personalised dosing and medicine.”
Ongoing journey
For the more than 250,000 people in the US living with a transplanted kidney, monitoring their organ’s health is an ongoing journey.
The easiest way to monitor kidney health is through measuring certain markers in the blood.
By tracking the patient’s creatinine and blood urea nitrogen levels, physicians can gain insight into kidney function.
But creatinine and blood urea nitrogen levels can fluctuate for reasons unrelated to organ rejection, so tracking these biomarkers is neither sensitive nor specific, sometimes leading to false negatives or positives.
The current ‘gold standard’ for detecting rejection is a biopsy, in which a physician uses a long needle to extract a tissue sample from the transplanted organ and then analyses the sample for signs of impending rejection.
But invasive procedures like biopsies carry risks of multiple complications, including bleeding, infection, pain and even inadvertent damage to nearby tissues.
Crucial
Gallon said: “The turnaround time can be quite long, and they are limited in monitoring frequencies and require off-site analysis.
“It might take four or five days to get results back. And those four or five days could be crucial in making a timely decision for the care of the patient.”
Northwestern’s new bioelectronic implant, by contrast, monitors something much simpler and more reliable: temperature.
Because temperature increases typically accompany inflammation, the researchers hypothesised that sensing anomalous temperature increases and unusual variations in temperature might provide an early warning sign for potential transplant rejection.
The animal study confirmed just that.
In the study, the researchers noticed that the local temperature of a transplanted kidney increases – sometimes as much as 0.6°C – preceding rejection events.
In animals without immunosuppressant medications, temperatures increased two or three days before biomarkers changed in blood samples.
In animals taking immunosuppressant medications, the temperature not only increased but also displayed additional variations as much as three weeks before creatinine and blood urea nitrogen increased.
Madhvapathy said: “Organ temperature fluctuates over a daily cycle under normal circumstances.
“We observed abnormal higher frequency temperature variations occurring over periods of eight and 12 hours in cases of transplant rejection.”
Gallon added: “Histological damage occurs even when creatinine is normal.
“Even though kidney function appears normal, the signs of rejection in the blood might be lagging a few days behind.”
Not only does the new device detect rejection signs earlier than other methods, it also offers continuous, real-time monitoring.
Right after transplant surgeries, patients might get blood tests more than once per week.
But, over time, blood tests become less frequent, leaving patients in the dark for weeks at a time.
The study is published in Science.
Image 1: Device implanted on a rat kidney. Credit: Surabhi Madhvapathy, Northwestern University.
Image 2: The tiny temperature implant is soft, flexible, and stretchable, conforming to the soft tissues of the kidney. Credit: Northwestern University.
