Bioengineered Human Kidney and Graft Technology Among New Innovations Highlighted at ASN Kidney Week 2023

A session at American Society of Nephrology (ASN) Kidney Week 2023 dedicated itself to emerging technologies in the realm of kidney replacement therapeutics. Featured speakers touched on the current technological innovations in nephrology as well as overviewed exciting developments in bioengineered therapeutic approaches.

Innovations in Dialysis Access: The Future Is Now

Monnie Wasse, MD, MPH, FASN, of Rush University, took the stage to provide an overview of the latest revolutions in vascular and venous access. As technological advances have continued in the realm of nephrology, Wasse presented on various grafts, arteriovenous fistula (AVF)–related topics, and other devices engineered to combat vein obstructions and address the needs of patients on dialysis.

Kidney Concept White | image credit: Inna - stock.adobe.com

The STARgraft AV Graft houses a synthetic expanded polytetrafluoroethylene (ePTFE) core that is externally coated with porous, soft silicone granules. This innovation uses a novel pore geometry that encourages capillary ingrowth and hinders fibrotic encapsulation. Furthermore, this graft aids in infection resistance and moves with pulsating blood while retaining wall compliance. These effects were clinically tested in a comparison of 73 STARgrafts against 27 control grafts.

A completely biological acellular vascular conduit (AVC) has also been engineered, referred to as the TRUE AVC. This is a nonimmunogenic, regenerative acellular conduit with a demonstrated bursting strength above 3000 mm Hg and a suture retention at rates above 150 grams of force. These data are backed up by the TRUE HD Study that took place in Paraguay and was assessed in 5 patients. At 26 weeks post intervention, there were no reported infections or aneurysms at follow-up and primary and secondary patency rates were high: 80% and 100%, respectively. Researchers have been pleased with these studies thus far as data show a good safety profile with low infection rates and nonimmunogenicity.

Wasse shifted her attention to the development of percutaneous/endovascular AVFs that create side to side anastomoses through deep vessels of the mid-forearm. This method can preserve upper arm vessels for AV access necessitated in the future. An endovascular/percutaneous (endoAVF/pAVF) AVF system she featured included the Ellipsys: an ultrasound-guided, single-catheter electrocautery device. This endoAVF was reported to have a cumulative patency rate of over 90% at 2 years.

Second generation pAVFs have also been developed; Wasse provided information on the Velocity device by Venova, which is designed for end to side anastomosis from the radial artery to the perforator. The pAVF achieves this without losing flow to the deep vnous system and is engineered to shift flow into superficial veins.

The second half of Wasse’s presentation mentioned wearable and balloon-delivered interventions, as well as devices to address central vein obstructions. These included the Alio Smartpatch, which the primary purpose of monitoring patients remotely. This patch is worn directly over dialysis access and takes readings on potassium levels, hemoglobin, oxygen saturation, and more every 3 hours. Data are uploaded to an online patient portal where clinicians can receive status updates.

Drug-coated balloon (DCB) angioplasty has shown promise in the treatment of mature AVF stenosis. These balloons are coated in paclitaxel, which is currently approved for AV access. This device inhibits smooth muscle remodeling and fibrosis, blocks the cell cycle during mitosis, and has a half-life lasting weeks to months. A multicenter, randomized, single-blind trial demonstrated that DCBs at 6 months exhibit over 20% increased patency rates compared with standard balloons used in angioplasty.

Wasse discussed the SAVE-US trial of patients with end-stage renal disease to showcase the efficacy of a surfacer inside-out access catheter system in venous obstructions. In a cohort of 30 patients, 53% of which had a stage 3 obstruction, 27 patients (3 were unable to receive the catheter) had successful interventions for right-sided placement—with no adverse events recorded.

These devices represent the many new treatment interventions and engineering explorations to aid patients affected by kidney disease and dialysis.

Human Kidney on a Chip: Disease Modeling, Drug Discovery and Clinical Trials

Jonathan Himmelfarb, MD, recent director of the Kidney Research Institute, expanded on the discussed innovations with his talk regarding the “kidney on a chip.” The development of this bioengineered human kidney model has paved the way for essential disease simulation and drug discoveries and development.

This journey started with the idea to somehow place human organs—human cells—on microchips as an alternative to animal testing to gather data on human genetics. The Nortis 3D Micro-Physiological System platform was an early innovation in this realm where researchers created 3-dimensional architecture and utilized fluidics to mimic, for example, the lymphatic system. As a consequence of these systems, eventually a bioengineered human proximal tubule was created on a chip in vitro. This was a huge development because the proximal tubule is crucial in kidney functioning. Himmelfarb continued to emphasize the importance of this type of modeling: “So the kidney is one of the most vascularized organs in the human body with 700 liters a day of blood flow. And we know that capillary action happens with almost any type of chronic progressive kidney disease.... If we can understand better the microvasculature, the peritubular, and the glomerular microvasculature. That's probably the key to preventing a lot of progressive kidney diseases.” With the ability to mimic these structures, researchers were able to model the effectiveness of drugs in vitro to develop candidate therapeutics that are very precise to the mechanistic action of disease processes.

One of these models successfully represented polycystic kidney disease (PKD). Utilizing the live cells from urine samples and reprogramming them into pluripotent stem cells enabled the development of a kidney organoid to carry out disease simulations like this one. This innovation was necessary because human genetics could not be modeled in the previous systems. Himmelfarb went on to share a timelapse video of an organoid engineered to mimic PKD being grown that was able to demonstrate cyst formation. Resources like this, he mentions, can change the course of studies in diseases like PKD because this cyst formation process had never previously been studied.

As their research progressed, they were also able to model COVID-19 infection of the kidney to demonstrate the organ itself does get infected—the proximal tubule cells get infected. Their success in these types of modeling could aid future research in, for example, the effects of long COVID in organs.

As his talk came to a close, Himmelfarb expressed his desire to have the “kidney on a chip” expand research efforts exploring the effects of aging on kidney functioning, as well as aid in knowledge surrounding drug dosing in patients. “We want to use these systems in every way we can to improve how we can delivery therapeutics to patients,” he concluded.