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Renal Replacement Therapy: Promising New Developments

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Rapid advances in biotechnology are opening the door to exciting new developments that have the potential to transform the treatment of end-stage renal disease. 

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The invention of the dialysis machine in 1943 revolutionized kidney care. Another revolution came in 1954 with the first successful human kidney transplantation. Since then, there have been incremental improvements in the treatment of end-stage renal disease (ESRD), such as the development of portable, in-home dialysis machines and improved antirejection drugs. 

But now, the rapid advances being made in biotechnology are opening the door to exciting new developments that have “the potential to transform treatment beyond dialysis and transplantation.” That’s according to an article published earlier this year in the Journal of Clinical Investigation.

That’s why we recommend you check out “Beyond Kidney Dialysis and Transplantation: What’s On the Horizon,” [1] in which authors Hamid Rabb, Kyungho Lee, and Chirag R. Parikh review five promising approaches to ESRD treatment. Following is a sample of what you’ll discover.

Wearable and bioartificial kidneys

These devices offer the potential for continuous, all-day dialysis with a high degree of comfort and convenience. 

In its latest form, the wearable artificial kidney is a belt-like device that is connected to blood vessels through catheters. The authors report:

“In a recent clinical trial [2], this device was tolerated for 24 hours without any serious complications, with effective uremic solute clearance.” And “study participants reported higher satisfaction with the wearable artificial kidney compared with conventional hemodialysis.” 

The bioartificial kidney is an implantable device that attaches directly to the patient’s systemic circulation and is powered by the patient’s blood pressure, thus eliminating the need for electric pumps. The device combines a silicon membrane blood filter with a bioreactor containing engineered renal tubular epithelial cells. According to the authors:

“The implantable bioartificial kidney is under preclinical testing [3] and has not yet been subjected to peer review, but the prototype silicon cartridge has been tested in canine models and showed sustainable patency without the need for an electrical pump or anticoagulants for up to one month.” 

Kidney-on-a-chip

This is an advanced microfluidics-based cell culture platform designed to mimic organ physiology. It has been used in nephrology medicine to reproduce tubular structures or glomeruli. Advances in 3D bioprinting have made possible the development of vascularized proximal tubule models. 

“This vascularized proximal tubule model [4] exhibited tubular reabsorption through tubular-vascular exchange, with potential applications in nephrotoxicity assessment and therapeutic development.” 

Furthermore, “An improved glomerulus-on-a-chip model that recapitulates the human glomerular filtration barrier has been developed from human podocytes and glomerular endothelial cells that are not separated by an artificial membrane, allowing direct cellular communication.” 

The next step is to develop chips that combine both elements to produce a functional nephron.

Xenotransplantation

Xenotransplantation—transplanting kidneys from domestic pigs—is a potential solution to the continuing shortage of donor organs. While promising, the technique involves numerous challenges. For example:

“Since humans have pre-formed antibodies against porcine xenoantigens, which cause hyperacute rejection, ‘triple-knockout’ pigs lacking three major xenoantigens (αGal, Neu5Gc, and SDa) were developed and are now used as a xenotransplantation model. Additionally, advanced genetically engineered pigs that have protective human transgenes ... are currently available and expected to further improve xenotransplantation outcomes.

“With remarkable advances in gene-editing technologies ... xenotransplantation outcomes in nonhuman primates have been continually improved, achieving recipient survival beyond one year.”

The authors reported that the first peer-reviewed, clinical-grade xenotransplantation study [5] had recently been published, in which a brain-dead human decedent underwent a bilateral nephrectomy followed by the transplantation of kidneys from genetically altered pigs. The study achieved only partial success:

“The recipient remained hemodynamically stable, with a viable graft, excreting urine ... However, the xenografts failed to achieve creatinine clearance and showed histologic evidence of thrombotic microangiopathy with uncertain etiology.”

The authors note that there are ethical, social, and religious concerns that must be addressed, and ...

“If xenotransplantation becomes clinically available, educational strategies for the general public and potential kidney transplant patient candidates and their families are likely to be required for its successful application.”

There is much more to be learned from this eye-opening article. [1] We recommend it. 

In the meantime, Healthmap will continue to work with our clients and their patients to make the most timely and appropriate use of available technologies and resources for better CKD and ESRD outcomes. We Are Committed to efficient kidney disease management. We Are Healthmap!




[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970661/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936831/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983406/
[4] https://pubmed.ncbi.nlm.nih.gov/30833403/
[5] https://pubmed.ncbi.nlm.nih.gov/35049121/

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