A List Of The Latest Progress Of Renal Replacement Therapy in 2023!

Methods of renal replacement therapy (RRT) include kidney dialysis or a kidney transplant. Although significant progress has been made in the treatment of kidney transplantation, due to the scarcity of kidney resources, accessibility is low. Currently, hemodialysis and peritoneal dialysis are treatments available in most countries, but treatment outcomes have not improved significantly. At the World Congress of Nephrology (WCN'23) in 2023, experts discussed 2 new RRT treatment modalities and believed that they may completely change the status quo of RRT. These two new RRT treatment methods are implanted bioartificial kidney and xenotransplantation. Furthermore, human decellularized blood vessels (HAV) and TURE decellularized vascular catheters (AVC) may revolutionize arteriovenous fistula establishment.

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Implantable Bioartificial Kidney

Professor William Fissell from Vanderbilt University in the United States is the former president of the American Society for Artificial Organs. He presented The Kidney project, an interdisciplinary, multicenter project to develop an implantable bioartificial kidney. It is worth noting that a prototype of an implantable bioartificial kidney has already been released in this project. So what is the mechanism of this prototype? How is the effect? When can it benefit the public?

1 mechanism

This implantable bioartificial kidney can be divided into two parts, namely the blood filter and the bioreactor. The hemofilter is similar to the current hemodialysis technology, and the bioreactor is mainly responsible for reabsorption, that is, reducing the amount of waste liquid/urine, which is close to the daily urine amount of normal people. A waste catheter is connected to the bladder and allows waste/urine to drain through the bladder and urethra.

However, a traditional hemofilter is bulky and cannot be implanted in the body, so The Kidney project developed a nanoscale silicon porous membrane, which reduces the overall volume of the artificial kidney. The siliceous membrane is similar to the glomerulus in that it blocks the passage of large molecules and allows the passage of small molecules.

To be implantable and work long-term in the body, the filtration mechanism of the implantable artificial kidney mimics the native kidney. The glomerulus is a network of capillaries surrounded by a tea-shaped structure (the glomerulus, also known as Bowman's capsule). As blood flows through these capillary networks, blood pressure is significantly higher than normal, allowing material in the blood to filter into primary urine. The artificial kidney uses the normal physiological phenomenon of differential blood pressure as the power source for blood filtration, thereby eliminating the blood pump (reducing volume). In addition, to maintain long-term use, the blood flow path inside the artificial kidney is made of special materials, which can reduce blood flow resistance and maintain blood flow perfusion pressure.

2 curative effect

At present, artificial kidney without adding a bioreactor has achieved preliminary success in an animal model (pig). In this study, the artificial kidney was attached subcutaneously or peritoneally to the pig (it was not implanted). It is worth noting that, in contrast to the need for immunosuppressive agents after traditional kidney transplantation, the pigs in this study received antiplatelet drugs and did not receive immunosuppressive agents. Compared with the pig model of renal failure, the artificial kidney can significantly improve the pig's blood volume and excrete excess body fluid.

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However, in this study, the artificial kidney without the addition of the bioreactor excreted too much body fluid, and some pigs developed hypovolemia. Therefore, experts believe that bioreactors need to be added to simulate the reabsorption function of renal tubules. The artificial kidney added to the bioreactor was successfully implanted in a 3D in vivo study. The animal model of this study was pigs. The implanted bioartificial kidney was composed of a 5nm silicon pore membrane and LLC-PK1 cells, which were produced by blood filtration. The rate of waste liquid is 4ul/min, the reabsorption rate of the bioreactor is 93%, and the cell activity is more than 95%.

This means that at present, there is a general-purpose (no need to match or use immunosuppressant) implantable bioartificial kidney that has no blood pump, can adjust the water-salt balance by itself, and has been successful in animal models. However, Professor William Fissell admits that the implantable bioartificial kidney will take more time to be commercially available. In the future, they will further reduce the size and prepare for related studies in humans.

xenotransplantation

Professor Robert Montgomery from NYU Langone Hospital in the United States introduced the xenotransplantation of kidneys. On September 25, 2021, NYU Langone Hospital completed the first implantation of a pig kidney into a human. On November 22, 2021, the hospital once again successfully implanted pig kidneys into humans. In the two cases of operation, the pig kidney could work stably in the human body for 54 hours. After the experiment, all pig kidneys underwent renal biopsy, which showed normal glomerular appearance, no microvascular inflammation, and no obvious lymphocytic infiltration in the interstitial tube.

Pig kidneys were well excreted in urine before study termination; eGFR doubled compared to baseline. There was no evidence of coagulopathy or disseminated intravascular coagulation, nor abnormal inflammatory or immune stress responses.

The pig kidneys used in the two operations were transgenic. The researchers added human complement inhibitory genes (hDAF and hCD46), human anticoagulant genes (hTBM and hEPCR), and human immune regulatory genes (hCD47 and hH01) to the transgenic pigs. , and the porcine carbohydrate antigen and porcine growth hormone receptor genes were knocked out, and these pigs had no erythrocyte antigen, suggesting that their organs are suitable for human patients of all blood types.

Related reading: ASN Kidney Week 2022 丨 Live! Making the impossible possible, the story behind the first successful case of pig kidney implantation into the human body

HAV and AVC

Professor Haimanot Wasse from Rush University Medical Center in the United States introduced human decellularized blood vessels (HAV) and TURE decellularized vascular catheters (AVC).

1 HAV

Although native arteries and veins are the first choices for vascular repair or establishment of arteriovenous fistulas, the condition of the patient's native vessels is often limited by their pathophysiological conditions. Consequently, synthetic vascular grafts, such as vascular materials composed of expanded polytetrafluoroethylene (ePTFE) or polyethylene terephthalate, have been implanted in millions of patients over the past 40 years, but their use comes with a higher risk of infection. Other vascular materials may not be available to patients due to several factors including availability, cost, processing technique, and other clinical circumstances. So, is there a more ideal material for vascular repair?

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HAV is made by inoculating human vascular cells onto a biocompatible, biodegradable mesh scaffold in a bioreactor. The specific production process can be divided into 2 steps:

① Within a few weeks after cell inoculation, the cells will gradually grow and form preliminary tissues. Thereafter, the mesh scaffold will degrade and blood vessels will form.

②Decellularize blood vessels to remove all cellular components that may induce immune responses, so that HAV cannot cause immune responses.

A Polish prospective phase II study (n = 40) demonstrated a high rate of HAV patency (58.2%), no infection, and good tolerance of HAV to repeated intubation during the 5-year follow-up period. Another study (n = 355) compared with expanded polytetrafluoroethylene (ePTFE) showed no significant difference in vascular patency between the PTFE and HAV groups at 6 and 12 months. In terms of group reactive antibody index and infection risk, ePTFE was significantly higher than HAV.

2 AVC

Another vascular repair material worthy of attention is TURE AVC. TURE AVC is a vascular repair material manufactured with 100% biotechnology without any other synthetic materials. It can withstand a pressure of 3000mmHg, can withstand a force of >150g at the suture, and is a material that does not induce an immune response.

The TURE HD study (NCT 049DSS11) is the first clinical study of TURE AVC, enrolling 5 patients with a brachial axillary catheter implanted for at least 4 weeks. The 5 patients had no infection or allergy, the patency rate of stage 1 was 80%, and the patency rate of stage 2 was 100%. HLA1 and HLA2 levels also did not change significantly.

In general, the above-mentioned new developments may completely change the status quo of RRT treatment shortly and benefit patients.

does eating cistanche good for the kidneys? what is the mechanism?

Cistanche is a traditional Chinese herb that has been used for centuries to support kidney health. Recent research has suggested that cistanche may have potential therapeutic effects on chronic kidney disease (CKD). The mechanism by which cistanche supports kidney health is thought to be due to its ability to increase blood flow to the kidneys, improve renal function, reduce inflammation and oxidative stress, and promote kidney cell regeneration. One of the key active constituents in cistanche is echinacoside, which has been shown to have a protective effect on the kidneys by reducing oxidative stress and improving renal function. Another active constituent, acteoside, has been shown to reduce inflammation in the kidneys and protect against kidney damage.

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While research on the specific mechanisms of cistanche's therapeutic effects on the kidney is ongoing, early studies suggest that it may be a promising natural remedy for supporting kidney health. However, as with any supplement or natural remedy, it is important to consult with a healthcare provider before use, especially if you have a history of kidney disease or are currently undergoing treatment for it.