Introduction
Currently, treatment for patients with end-stage renal disease is a renal transplant or dialysis if a donor's kidney is unavailable. However, the excess need for transplants and lesser donor kidney availability with transplant complications like infections, cancer development, and limited mobility have led to the development of alternative renal replacement technology.
What Is Kidney Replacement Technology?
In the past two decades, there has been tremendous growth in renal replacement technology due to improvements in nanotechnology, cell growth, and bioreactors. Recent advancements in kidney replacement technology include implantable bioartificial kidney (BAK) and kidney regeneration technology. The research regarding these techniques is in the preclinical stages; they are being developed to replace kidney functionality. The replacement technology can overcome donor kidney shortages and complications of transplantation and immunosuppressant (reduced immune system) therapy.
Why Was Renal Replacement Technology Developed?
Kidney failure due to end-stage renal disease is treated with a kidney transplant. If the donor's kidneys are unavailable, most patients undergo hemodialysis or peritoneal dialysis. Although dialysis can improve kidney filtration, there is no improvement in renal metabolic, endocrine, and reclamation function, leading to poor outcomes. Dialysis does show significant improvement in morbidity or mortality risk. Therefore, it led to research on newer treatment methods to reclaim complete kidney function. Two models were developed: automated wearable artificial kidneys (AWAK) and wearable artificial kidneys (WAK).
AWAK is a peritoneal dialysis-based artificial kidney and uses dialysate regeneration to lower fluid requirements. The artificial kidney contains tubing, a disposable storage module, and a system controller that is compacted into a device the size of a handbag. The dialysate is infused into the peritoneal cavity and is responsible for absorbing waste products, toxins, and fluid through the peritoneal membrane. The regenerated dialysate returns to the peritoneal cavity, and the filtrate is drained through an ultrafiltration bag and discarded. The process is repeated when the cartridge is replaced with a new one. This device is approved for human trials.
WAK is a portable blood-based renal device. The device is battery-operated and is worn around like a belt or vest. Heparin is added through a syringe pump to prevent the coagulation of blood flowing through the device. The blood then passes through the two-channel pump, pushing the blood and dialyzer toward a small dialyzer. When the blood exits the dialyzer, it passes through a bubble detector before it returns to the patient. Most of the dialysate is regenerated, and a part of it is removed by an ultrafiltration bag for disposal. This device is authorized for clinical trials.
Both devices can achieve complete kidney functions and are established on ultrafiltration techniques. However, they are lifestyle-limiting and require extra machinery systems that could limit patients’ mobility. The methods do not significantly improve the endocrine and metabolic function of kidneys, resulting in poorer outcomes over some time.
Therefore, newer techniques like AWAK and WAK were designed to restore kidney function and improve patient mobility to overcome limitations.
What Is BAK?
It is a newer method for the treatment of end-stage renal disease. The procedure is less time-consuming and can replace total kidney function. The blood undergoes ultrafiltration to remove toxins and retain albumin. The filtrate passes through a renal tube where additional water and solutes are reabsorbed. BAK contains a highly functional filter connected to cultured renal tubule epithelial cells. In the device, the solute is transferred with convective transport and depends on a hydraulic gradient for passage through the membrane—the conceptive transport functions on blood pressure. The device is implantable and mimics the natural kidney function.
Limitation
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There is a challenge to create a miniature version of implantable BAK.
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To design a device with maximum water permeability and reduced leakage of albumin and other macromolecules.
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To prevent coagulation of blood in the long term.
What Is Kidney Regeneration Technology?
Advancements in stem cell therapy and developmental biology have helped develop a transplantable kidney graft from the patient’s cells. Controlled stem cell differentiation can form an autologous kidney regeneration.
Scaffolding is the method used in kidney regeneration. An ECM scaffold can provide three-dimensional support to specific organ cells and their vasculature. However, creating a scaffold with a structure, complexity, and size similar to a human kidney is challenging. Detergent-based perfusion decellularization of the mammalian organ can be distilled into an ECM scaffold using the formulated solution. However, human kidneys require a careful examination of the composition, growth factor level, and mechanical properties of developing organs.
Rat kidney decellularization with detergent perfusion could successfully create a whole organ scaffold. It preserved the structure and function of the ECM (extracellular matrix) scaffold with its filtration, secretion, and reabsorption properties. The decellularized scaffolds are inoculated with endothelial and epithelial cells formed from baseline stem cells to create functional kidney grafts. The bioengineered kidney is transplanted in an orthotopic position. The urine formation is normal.
The technology is currently in the preclinical trial stage. Alternatively, a cadaveric kidney is decellularized to create scaffolds. The scaffolds can be recellularized with endothelial and epithelial cells and matured in a bioreactor to form a functional kidney. The kidney is transplanted in an orthotopic position to restore kidney function.
The perfusion decellularization method can be used in the three-dimensional bioprinting of kidneys. A specific bio-ink is needed in a particular setting to induce cellular growth and proliferation. If this technique is implemented clinically, it mitigates the need for immunosuppressive drugs.
What Are the Benefits of Renal Replacement Technology?
The benefits of renal replacement technology include:
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Addresses the issue of donor organ shortage.
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Reduces the need for immunosuppressive drugs.
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The patient's mobility and complete kidney function can be restored.
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Reduces the risk of renal cell carcinoma in transplant or long-term dialysis patients.
What Is the Outlook for Renal Replacement Technology?
Currently, BAK and renal regeneration methods are in the preclinical stage of development. The clinical application of these methods can significantly improve the patient's quality of life and reduce mortality.
Conclusion
Newer innovations in renal replacement technology can be an alternative treatment method for end-stage renal disease. The alternative methods can restore complete kidney function and improve patient mobility. The techniques can help overcome complications or transplants and prevent renal cancer. Further research is needed to apply these techniques clinically.
