Implantable Bio Artificial Kidney, an innovation in Renal Treatment

Summary

End Stage Renal Disease is a chronic kidney ailment that generally culminates in kidney failure. In such a scenario, a kidney transplant is the ideal treatment. However, given the low availability of kidneys or kidney donors, dialysis is the only other alternative. Unfortunately, both transplantation and dialysis have their own limitations and come with high risk of morbidity and mortality. Bio Artificial Kidney is a refreshingly new alternative which overcomes all those limitations, and mimics almost all the functionalities of a natural kidney. In this article, we will learn more.

Introduction to ESRD

Kidney failure, technically called as End Stage Renal Disease (ESRD) is becoming increasingly common, with nearly 4.7 million people being diagnosed with the problem and receiving treatment in 2021 alone. There are various risk factors for ESRD including type-2 diabetes, hypertension, drug-abuse, cardiovascular ailments, blockages in the urinary tract, inflammation due to one or more reasons/ailments, a family history of kidney failure, and some genetic disorders. Covid-19 infection has also been a risk factor in recent cases.

Once kidney failure is imminent, quick action must be taken, else the condition can be fatal. The ideal solution would be a kidney transplant. However, worldwide, there is higher demand than supply of cadaver kidneys (kidneys taken from recently deceased people) or live donors who can donate a kidney. In such a scenario, the person is put on a waiting list for kidney transplantation, and till then, he must undergo dialysis (technically called haemodialysis) regularly. In dialysis, the person’s blood is taken out of the body, cleaned or filtered in an external machine, and then returned to the person’s body.

Limitations of above treatments

Kidney transplantation

Kidney transplant comes with its own risks such as:

• Rejection of the donated kidney by the body
• Bleeding (haemorrhage) and blood clots (thrombosis)
• Infections or a cancer passed on by the transplanted kidney
• Leaking from ureters

Of all these, the first reason is the most important. The body’s immune system treats the new kidney as an alien body and keeps attacking it again and again with an aim of destroying it. To overcome this, the recipient must take immune-suppressant drugs all his/her life to suppress the immune system. This itself adds more load on both kidneys. Further, it makes the person vulnerable to infections and various ailments.

Haemodialysis

Intermittent dialysis that is done 3 or 4 times a week in a clinic comes with its own share of risks.

• If an excessive or insufficient amount of potassium is eliminated in the process of dialysis, it could lead to irregular heartbeats or even cardiac arrest.
• Complications at the access site such as infection, narrowing of blood-vessels (stenosis), and ballooning of blood-vessel walls (aneurysm), or total blockage of the blood vessel.
• Extreme fatigue for the patient
• Poor sleep
• Transit or schedule-related difficulties
• Accumulation of fluids, electrolytes and toxins on the other days when dialysis is not done
• Less dialysis time can cause hyperphosphatemia (high phosphorus levels in the blood) and malnutrition
• The above two are huge risk factors for CVS morbidity and mortality.

Home dialysis that is done daily, slightly overcomes some of these limitations.

However, the most important limitation is that, dialysis can only perform the excretory and filtration functions of the kidney as well as correct any fluid and electrolyte imbalances. That too partially. For example, the filtration function is not comprehensive or complete. Protein-bound uremic toxins (PBUT) and wastes or toxins that are made of large molecules do not get filtered, due to limitations in pore size of the membranes used in dialysis machines. Dialysis cannot perform the other kidney functions which are endocrine, metabolic and secretory in nature.

Recent innovations

To overcome the limitations of haemodialysis, there have been various experiments in creating artificial or man-made kidneys which mimic all or most of the functions of natural kidneys. These experiments started in the early 2000s and led to products such as PAK (portable artificial kidney), AWAK (automatic wearable artificial kidney) and BAK (Bio-Artificial kidney). Various prototypes of these products are in various stages of research and clinical trials. Some of them are:

• Renal assist device (RAD)
• Human nephron filter (HNF)
• Bioartificial Renal Epithelial Cell System (BRECS)

Most of these products are worn outside the body, which requires the person or wearer to drain out the ultrafiltrate (urine) regularly. This factor, plus the weight of the devices and the unnecessary attention that it draws are some of the reasons why PAK and WAK are not preferred by everybody.

This is what led to the creation of an implantable BAK, a project carried out at UCSF (University of California at San Francisco) by a nephrologist named Dr. William H. Fissell, M.D., and Dr. Shuvo Roy, Ph.D., a professor of bioengineering at this university.

implantable Bio-Artificial Kidney (iBAK)

The iBAK is a small compact device roughly the size of a natural kidney. It perfectly substitutes the diseased kidney inside the body, and is implanted in the same location. Connections to the renal artery and vein are made to the device, just like with a natural kidney. So also, a connecting pipe to the urinary bladder mimics the role of a ureter which is part of a natural urinary system.

The device filters out uremic toxins from the blood, in addition to replicating the tubular functions of a natural kidney such as selective reabsorption of water and salts. A one-time surgery is undertaken to implant the iBAK. This helps establish a permanent blood connection between the device and the iliac blood-vessels. After this, the iBAK filters blood continuously, which overcomes all the hassle and risks that come with intermittent haemodialysis.

The bioartificial kidney is a two-stage system that consists of

1. A hemofiltration unit to remove toxins: To achieve this, silicon nanotechnology is harnessed to create a highly efficient and compact membrane. This relies on the body’s natural blood-pressure to perform ultrafiltration without having to provide pumps or power supply.
2. A renal cell bioreactor to mimic the other biological functions of a natural kidney: This includes delivering oxygen and nutrients to kidney cells while protecting them from the recipient’s immune system that can cause rejection. To achieve such immune-protection, the membranes used in the hemofiltration unit are less than 1 μm to filter out the immune cells of the recipient’s body. Further, the cells used in the Renal cell bioreactor are cultured in a lab using the patient’s own cells and placed in the bioreactor in a special compartment isolated from the recipient’s bloodstream. This implies the recipient will not need to take immunosuppressant drugs all his life, like with a renal transplant.

The silicon membranes used in the first component have been engineered and tested to ensure efficient filtering of toxins at natural blood-pressure levels. The material used in the membrane materials have also been evaluated for bio-safety, and compatibility with blood, so that unnecessary coagulation (blood-clots) does not happen.

For the second component, a reliable supply of healthy cells derived from the recipient’s body and preserved at sub-zero temperatures (cryopreservation techniques) are used. Experiments conducted on these cells in a miniature bioreactor in a laboratory have shown biological activity, including: the ability of selective reabsorption of water, as well as providing a barrier to urea and creatinine, for as long as 2 months. All these establish the effectiveness of the bioreactor.

This way, by replicating all the functionalities of a healthy kidney, iBAK eliminates the need for constant supervision by a doctor, and heavy doses of immunosuppressant medication, both of which make it an excellent alternative to having a natural kidney, and a much better option that transplantation or dialysis. Although the iBAK is not yet widely implanted or available today, its adoption is increasing year on year. This offers hope to millions of patients worldwide who are diagnosed with ESRD every year.

 

Kauvery Hospital is globally known for its multidisciplinary services at all its Centers of Excellence, and for its comprehensive, Avant-Grade technology, especially in diagnostics and remedial care in heart diseases, transplantation, vascular and neurosciences medicine. Located in the heart of Trichy (Tennur, Royal Road and Alexandria Road (Cantonment), Chennai (Alwarpet & Vadapalani), Hosur, Salem, Tirunelveli and Bengaluru, the hospital also renders adult and pediatric trauma care.

Chennai Alwarpet – 044 4000 6000 •  Chennai Vadapalani – 044 4000 6000 • Trichy – Cantonment – 0431 4077777 • Trichy – Heartcity – 0431 4003500 • Trichy – Tennur – 0431 4022555 • Hosur – 04344 272727 • Salem – 0427 2677777 • Tirunelveli – 0462 4006000 • Bengaluru – 080 6801 6801