Implantable Biosensors & Wearables for Kidney, Urologic Diseases

Biosensors may turn into a new clinician assistant by providing earlier detection of kidney-relevant biomarkers, such as creatinine, urea, and electrolytes in peripheral body fluids. Implantable systems may help in the identification of early transplant rejection through analysis of organ temperature and perfusion. A recent review article published in Nature details remarkable progress in wearable technologies that aims to deliver key biological data accurately and fast to transform patient care.

“The wearable sensors are just around the bend. The implantable devices will likely take some years due to the regulatory pathway,” said corresponding author John Rogers, PhD, who is a professor at Northwestern University in Evanston, Illinois.

The promise of biosensor technologies may be their ability to enable continuous, real-time monitoring of kidney health. This could offer complementary information to standard clinical procedures and alert physicians of changes in kidney health for early intervention. Home monitoring will have a pivotal role for sustainable kidney care and optimization of patient outcomes. New bioelectronics are now poised to help improve the management of chronic kidney disease (CKD), acute kidney injury (AKI), and allograft health biophysical properties of kidney tissue.

Commercial translations of wearable biosensing devices are expected to benefit patients by reducing costs and providing invaluable real-time biochemical information for clinical decision-making. “We and others have active collaborations with nephrologists, and in several cases the devices have been used with human subjects. With only a few exceptions, these technologies are not, however, currently being used in clinical decision-making simply because they have not yet been passed through the FDA process,” said Dr Rogers, who has inventions leading to more than 80 patents and patent applications with more than 50 licensed or in active use.

Chronic Kidney Disease and Kidney Transplantation

Implantable sensors may provide real-time data on kidney tissue properties like oxygenation, perfusion, and temperature, which are critical for early detection of transplant rejection and AKI. “Biosensors for kidney health are highly promising and are on a clear trajectory toward clinical integration, though widespread adoption may still take a few years. I believe it may take 3 to 5 years as well,” said Vishnuram Abhinav, a PhD student at the University of Bath, UK. “Recent advances in wearable and implantable bioelectronics have demonstrated the ability to continuously and non-invasively monitor key renal biomarkers such as creatinine, urea, and electrolytes in peripheral biofluids.” 

Currently, nano-warming techniques are under investigation. These tools offer the promise of uniform, rapid warming of the donated kidney right before transplantation in the recipient. Investigators are testing placing fiber optic temperature probes in the hilum, medulla, cortex and outside the kidney to record temperature distributions. 

“Currently, nephrologists are beginning to incorporate wearable biosensors into clinical practice, primarily in specialized centers and research studies focused on chronic kidney disease (CKD) and transplant monitoring. Non-invasive devices that measure biomarkers in sweat or interstitial fluid are gaining traction due to their ease of use and patient comfort,” said Abhinav. 

Implantable sensors currently remain largely in the experimental phase pending further clinical validation. In the next 12-18 months, it is anticipated refinements will include improved sensor sensitivity and specificity for key renal biomarkers to enhance early disease detection. Also anticipated is the integration of multi-modal sensing (biochemical plus biophysical parameters) to provide a more comprehensive picture of kidney health. 

Faheem Ershad, PhD, who is an assistant professor in the department of Electrical and Computer Engineering at the University of Houston in Texas, said soft biosensors are extremely promising in that they circumvent the limitations of blood tests, urine tests, and biopsies, which typically involve infrequent and inconsistent sampling. “These traditional methods are also highly invasive. On the wearable biosensors front, researchers working in bioelectronics have already been able to measure various kidney-related biomarkers in sweat, interstitial fluid, saliva, or tears using flexible, patch-type devices with integrated microfluidics and sensing elements,” said Dr Ershad. “These sensors can already achieve high specificity and selectivity for detecting kidney disease biomarkers. Creatinine and urea are the most common target analytes, typically detected using optical or electrochemical approaches.”

Dr Ershad noted there are still significant challenges remaining for wearable biosensors in validating accuracy and clinical utility. These approaches need to ensure that biomarker/metabolite levels in sweat or interstitial fluid reliably correlate with blood levels. “Sensor biofouling and long-term stability also remain longstanding challenges. Finally, applying sufficient power and integrating AI-driven processing need to be improved and added to these devices for long-term monitoring at the clinical level so they can truly benefit medical decision-making by doctors,” said Dr Ershad.

Bladder Sensing and Surgery Recovery

For urologists, there has not been as much development in bioelectronics. Dr Ershad said sensors have been developed to monitor in real-time bladder pressure and volume in rodents and primates. “There is an effort to develop stimulators for the bladder to induce urination on demand, but this work is relatively nascent. Sacral neuromodulation is another approach that has seen some development in the field of bioelectronics, where researchers are developing pacemaker-like implants that are battery-free and so low-profile that they can be inserted into the body via needles,” said Dr Ershad. 

In addition, a randomized trial recently published in NPJ Digital Medicine compared remote perioperative telemonitoring care versus surgeon-only care in patients with genitourinary, gynecological, or gastrointestinal cancers. All patients wore a wristband accelerometer to measure functional recovery from cancer surgery for 3 months and also reported symptoms via a mobile application. In the intervention group, triage nurses telephoned patients when sensor and other patient-reported data did not meet recovery thresholds. The control group received only automated messages for poor recovery. The postoperative functional recovery rate and symptom severity improved when sensor and other patient data prompted clinical phone calls. The control group received only automated messages for poor recovery. “It’s the human response to these data that makes the difference,” said trial coauthor Tracy Crane, PhD, RDN, of the Cancer Control Program, Sylvester Comprehensive Cancer Center, University of Miami in Florida. 

Toward Clinical Use

It is expected that more biosensor devices will be capable of multiple functions in a single package. For example, a single skin patch to measure sweat creatinine, glucose, and electrophysiology. “We’re beginning to see the first clinical uses of these devices in niche or early-access settings. In the next 12 to 18 months, I anticipate a significant increase in human trials and early clinical translation. I also believe that improvements in wireless power, bioresorbability for temporary-functioning devices, and material properties will be achieved during this time,” said Dr Ershad. 

He expects more commercial launches to occur alongside an increase in deploying AI to detect patterns and predict adverse events. The transition of biosensors from experimental tools to standard-of-care devices may take another 12 to 24 months, due to clinical validation and regulatory approval.  

“We are not using it yet. I think the trend is toward tailored therapies. I certainly see a big opportunity. We will be able to start to intervene earlier and catch things quicker,” said Robert E. Weiss, MD, who is professor and chief of urology at Rutgers-New Jersey Medical School in New Brunswick, New Jersey. 

Fokko Wieringa, PhD, is the principal scientist within the health department of IMEC the Netherlands, and a part-time associate professor of medical technology at University Medical Center Utrecht, the Netherlands. Dr Wieringa said the challenges for successful innovation are not only technological and biological, but also financial and regulatory. “The lowest hanging fruit would be implantable sensors for core temperature, blood pressure, and blood flow, all with wireless charging and well-protected communication,” he said. “Of course, such implants should preferably be MRI-compatible. Various chemical sensors are already at hand, but they are all hampered in duration by membrane fouling and encapsulation of foreign matter. We are working on a solution to that, but it is not yet solved.”

Dr Crane said that this is an opportunity for innovation. “Tomorrow’s providers should be comfortable with data streams from connected devices to harness these data and collaborate across disciplines, putting patients at the center of every decision. Technology can help us do this.”

Disclosure: Some sources declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of authors’ disclosures.