Category: Kidney

No matter how we practise healthy habits and how much we care about our body, there are certain occasions which may react to our body itself against us. The kidney stones are one of a challenging thing similar to this. So, since this can be a caused to arise unbearable pain, the best practice is to follow preventive measures before arising the need for curing. Often, health care professionals may help you to identify a number of effective measures to prevent the formation of kidney stones. Actually, these include drinking adequate amount of water per day, healthy diet latter and lifestyle modifications. But, instead, if that nowadays using essential ouls for kidney stone is also a common practice. Thus, here we have customised a small piece of writing to share everything you need to know on this. Ultimately we hope, it will help you to prevent further exposes.

Lemongrass

Over the years the people used to apply this oil as the best solution to kidney stones. It says this oil varies can boost the blood supply to the areas with massive pains. So, it indirectly helps the removal of waste products and the supply of nutrients. Thus, regular usage of this regime may definitely help you to control the pain and discomfort at the back where kidney lies.

Lemon

The natural detoxifying features and ability to fight against free radicle formation are the best two features of lemon in relation to kidney problems. So, it will boost the kidney functions and will destroy the toxic materials which have ingested through foods in the liver. So, gradually, it reduces vulnerability for calcium deposits inside the internal body.

Orange

This also holds similar properties as with the oils taken by concentration lemon fruit parts. Further, this is very much popular as a natural diuretic in many kinds of books and guides which have designed by experts. Not only that lots of latest researches have revealed its effect on fighting to reduce pain around the area by minimising muscular spams occurred dues to stone movement.

Helichrysum

Actually, most of the similar properties we discussed earlier is validated for this measure as well. Thus, often, the ability to minimize inflammation and the ability to dilute the urine by ensuring easy passage to calcium balls are the admirable qualities of this oil variety.

Lavender

Often, this is known as the most innocent member of essential oil family as it had a more pleasant fragrance. Thus, it helps everyone to stay calm and relax. Since mental stress also plays a massive role in the formation of these calcium stones, you may use this solution to awake the happiness.

At last, it is good to think of the best methods to have these regimes. Isn’t it? Otherwise, it may become a stage of your time without notable benefits. So, you may apply the oils in three ways.

The first one is the topical application which helps more in minimizing pain. Further, it can apply through respiratory pathways by using a diffuser. Or else, you may use pills or home remedies to gave it through oral ingestion methods. Actually, all these three ways have up and down beneficence on bodily functions.

The final message to share

Even though kidney problems has become one of the most common health impairment in this era, it is actually categorised under preventable issues. So, it is good to keep updating with the best essential oil for kidney stones to share the information with others who need help. But, keep in mind to practice all other preventable measures at once to have the most effective outcomes.

Chronic kidney disease (CKD) is a condition characterized by loss of kidney function over time. The kidneys play a vital role as an excretory organ and are crucial in managing the homeostasis of endocrine, fluid, electrolyte, mineral and acid-base balancei. The deterioration of the kidney’s ability to function makes nutritional derangement inevitable in patients with CKD. Because of this impact, the nutrition care process is an important component of treatment, which can help slow and prevent the progression of CKD.

The nutrition care process is a systematic approach towards providing optimal management and incorporates the following 4 steps: assessment, diagnosis, intervention and monitoring. This process can be applied to any nutrition-related condition and allows for individualised care rather than over-generalising. It is important that we treat these cases individually due to differing biochemistry, the stage they’re in and how much stress it has already caused other organs.

Sadly, CKD cannot be cured as the nephrons that make up the kidney are non-regenerative, much like the brain. If it progresses to end stage renal disease, hemodialysis or peritoneal dialysis will be needed or if the opportunity arises, a kidney transplant. It is important to understand that these treatments are not a cure, as donated kidneys eventually fail and dialysis cannot replace all its much-needed functions, so to improve outcomes, dietary change is crucial in delaying further health consequences.

The National Kidney Foundation state that the populations who have a high risk of developing CKD include people with diabetes, hypertension, cardiovascular disease and obesity. In diabetes smaller blood vessels are greatly affected by high blood sugar, including in the ones located in the kidney. In Australia, 1 in 3 people have an increased risk of developing CDK and can lose up to 90% of kidney function before experiencing their first symptom. The most recent study done about people with end stage renal disease was in 2013, and showed a staggering increase of 51% since 1997. The Indigenous population are at a much-increased risk of developing CKD and are hospitalised more frequently than non-Indigenous Australians. This is because they have a higher prevalence of diabetes, cardiovascular disease, alcohol abuse and inadequate nutrition as well as lack of awareness. Of the Indigenous population they are 4 times more likely to die of CKD than the general population.

There are many barriers that prohibit the body from receiving optimal nutrition with CKD. Due to kidney malfunction, the body will experience toxicity overload as it is struggles to regulate homeostasis. As sufferers of CKD may not be symptomatic up to %90 kidney failure, it is imperative that advise be taken gravely. Minor dietary augmentation will be prescribed at first, as the disease progresses the change of diet will be crucial. Kidney function is estimated using glomerular function rate which is calculated using creatine levels, age and gender. Depending on biochemistry results, the following nutrients are affected in someone with CKD: sodium, phosphorus, potassium, protein, calcium, 1,25-dihydroxy vitamin D and fluids

CKD sufferers are prohibited from uptake of 1,25-dihydroxy vitamin D and in turn phosphorus will begin to build-up in the blood resulting in hyperphosphatemia. It is important that the phosphorus intake is in its organic state from foods, as only 40-60% is absorbed, whereas 90% of inorganic phosphorus from additives is absorbed. In the body, phosphorus binds with calcium in the body to build and maintain bone structure, if it runs out of calcium in the blood the parathyroid glands will leach calcium from bones to maintain homeostasis. This increases the risk of ectopic calcification and risk of osteoporosis. Although calcium is important, the majority of foods high in calcium are also high is phosphorus, so doctors usually recommend a calcium supplement.

High blood pressure can cause intraglomerular pressure within the kidney, so limitation of the consumption of sodium is recommended from beginning of treatment, regardless of CDK progression. Hypernatremia will cause increased fluid retention whilst also contributing to hypoalbuminemia which can further progress CKD. It’s important that patients read labels carefully as foods low in sodium are replaced with potassium chloride. Sodium is limited to 2300mg a day.

Advanced stages of CKD result in hyperkalemia as the kidneys struggle to excrete excess potassium. The kidneys are responsible for excreting 90% of the potassium that is consumed daily, with the remaining 10% excreted by feces. As potassium is an electrolyte, abnormal levels are dangerous and cause heart arrhythmias. The recommended intake is 2000-2500 mg a day.

The recommended energy intake is the same for all stages of CKD, with a range of 126-147 kJ/kg of ideal body weight (IBW). We use IBW, as actual body weight can be hard to determine due to edema which most people will experience. Use of current body weight for someone who is underweight or overweight may under or overestimate nutrient needs. That is why we need to use clinical judgement.

In early stages of the disease the kidneys struggle to excrete protein waste. Damage prevention by lowering protein intake is recommended in lieu of excluding. On the other hand if someone is on dialysis, there needs to be an increase in certain proteins as the process can strip away essential amino acids. The protein intake is fixed at 0.75 – 1g/kg IBW in stages 1-4. In a patient on dialysis it is increased to 1.2g/kg to make up for unintentional losses during treatment for both hemo and peritoneal dialysis. In peritoneal dialysis the lining of the abdomen is used as a natural filter. If this lining becomes inflamed the protein intake is further increased to 1.5g/kg as the patient can lose up to 15g in a session. If the person has complications of diabetes, sugars and carbohydrates need to be monitored with all of the above.

Fluids are not usually restricted until stage 5 (ESRD). For someone on hemodialysis there is an allowance of 500ml/day plus the past day’s urinary output. Peritoneal dialysis allows for a further of 250ml per day.

Anemia is common in CKD because of the reduced production of erythropoietin, an essential hormone that facilitates the production of red blood cells. Although dietary intake cannot solve this, erythropoiesis stimulating agents are supplemented.

Although there are other constraints to evaluate, these are the most commonly reviewed nutrients in scientific renal articles. Renal diseases are a difficult area to manage but without precision and use of dietary support, there can be drastic effects on both the patient’s health and mortality.

References

1. Academy of Nutrition and Dietetics. (Producer). (2019). Certificate of Training: Chronic Kidney Disease Nutrition Management [Online training program]. Retrieved from ‘ https://www.eatrightstore.org/cpe-opportunities/certificates-of-training’
2. Australian Indigenous HealthInfoNet. (2018). Chronic Kidney Disease. [online] Available at: https://healthinfonet.ecu.edu.au/learn/health-topics/kidney/chronic-kidney-disease/ [Accessed 18 Feb. 2019].
3. Australian Institute of Health and Welfare. (2019). Chronic kidney disease compendium, How many Australians have chronic kidney disease? – Australian Institute of Health and Welfare. [online] Available at: https://www.aihw.gov.au/reports/chronic-kidney-disease/chronic-kidney-disease-compendium/contents/how-many-australians-have-chronic-kidney-disease [Accessed 2 May 2019].
4. Byham-Gray, L., Burrowes, J. and Chertow, G. (2014). Nutrition in Kidney Disease. 2nd ed. New York [u.a.]: Humana Press, pp.1, 10-12.
5. Byham-Gray, L., Stover, J. and Wiesen, K. (2013). A Clinical Guide to Nutrition Care in Kidney Disease. 2nd ed. Chicago, Ill.: Academy of Nutrition and Dietetics, pp.13-17, 27, 263.
6. Dr. Kamyar Kalantar-Zadeh, University of California Irvine, USA; speaking at the Karolinska Institute Advanced Renal Nutrition Conference 2013, Stockholm
7. Kidney Health Australia Kidney Fast Facts. (2018). [ebook] Melbourne: Kidney Health Australia, pp.1-2. Available at: https://kidney.org.au/cms_uploads/docs/kidney-health-australia-kidney-fast-facts-fact-sheet.pdf [Accessed 9 May 2019].
8. Mitch, W. and Ikizler, T. (2010). Handbook of Nutrition and the Kidney. 6th ed. Philadelphia, PA: Lippincott William & Wilkins, pp.12,13.
9. What is Chronic Kidney Disease – Indigenous Fact Sheet. (2016). [ebook] Kidney Health Australia. Available at: https://kidney.org.au/cms_uploads/docs/kidney-health-australia–what-is-chronic-kidney-disease.pdf [Accessed 18 Feb. 2019].

Chronic Kidney Disease

Chronic kidney disease (CKD) is a condition where the kidneys lose their function over a period of time. This disease is also known as chronic renal disease. If it develops and takes place in a host’s body, it may result to kidney failure due to no treatment, which later would need immediate dialysis or a transplant, as the kidney will not allow the blood to be filtered. It is called “chronic” as it develops in the host’s body over a long period of time, damaging their kidneys and its functions.

Our kidneys help maintain and filter our blood and body every day. The kidneys help stabilize salts and minerals that run in our blood, such as potassium, sodium, calcium and a few more. Another function that the kidney serves for the body, is the hormones. Kidneys help develop and make hormones in the body that help maintain blood pressure.

How is Chronic Kidney Disease Diagnosed and Developed in a Human Body?

CKD has many causes, the top 2 being diabetes and high blood pressure. If a human body is diagnosed with diabetes, the bodies can result to high blood sugar which later leads to damaged organs, 1 of them being the kidneys and its blood vessels. Almost 23% which is 1 out of every 3 people who have diabetes suffer from CKD.

High blood pressure, if caused can damage blood vessels around the body. If not treated and continued, it can reduce the blood supply given to organs such as the kidneys. High blood pressure also damages the kidney’s small filtering units which later develops CKD. 1 in every 5 people with high blood pressure, are diagnosed with CKD.

Chronic kidney disease can also be caused and developed depending on the history of CKD in your family, drug intake of the host and many different syndromes such as hemolytic uremic syndrome (low in red blood cells and platelets, leading to kidney failure). Almost 661,000 Americans suffer from kidney failure. And out of these individuals, 468,000 people are put on dialysis and around 193,00 live with the help of kidney transplants.

Chronic kidney disease is fatal (deadly) if not treated with a transplant or proper dialysis or treatment. Not treating this disease can progress to end stage kidney failure. Without proper dialysis, treatment or transplant, the patient can only survive only days to weeks. Since CKD is common, over the past years and decades new treatments and procedures have been developed to help cure the patient.

Chronic Kidney Disease and the Human Body

Kidney diseases, CKD specifically has many complications and effects on the body. Due to the waste products and fluid that build up in your body can leave the patient with nausea, lack of sleep, short breaths, swellness on the ankles and so on. CKD also attacks and damages the systems inside the body. Because of the kidney losing its function of filtering waste, dangerous and toxic levels of waste can be mixed and connected that causes the blood’s chemicals going out of balance. CKD also weakens the immune system, due to the buildup of waste causing the patient to catch an infection easily and quickly.

Chronic kidney disease affects two main parts of the kidney, the glomerulus and tubules. The kidneys have millions of glomeruli, these are tiny blood vessels through which blood is pumped. The glomeruli helps pump out unneeded substances such as wastes that are not needed by the body, this fluid is then collected in the tubules. The tubules help filter the fluid more keeping the substances the body needs and disposing of what’s not needed. “In CKD, this filtration process breaks down and so the glomeruli and tubules do not work as well. Toxins (such as urea) can start to build up and cause problems, and the kidneys can start to ‘leak’ protein into the urine” (‘Chronic Renal Failure (Kidney Failure) Information | Myvmc’).

Stem Cells and Chronic Kidney Disease

A new treatment and cure is being developed to help patients with chronic kidney disease. Stem cell treatment is a new type of therapy being investigated to reduce the need of dialysis and transplantation. Today, mostly many universities around the world are finding out if stem cells can be used to improve the critical condition. These investigations and trials are taking place around the world, mostly the United States. Mesenchymal a type of stem cell, found in the bone marrow is said to be used for this treatment due to its characteristics and features.

How Stems Cells will be used to treat Chronic Kidney Disease

Based on Harvard Stem Cell Institute (HSCI), during their investigation, they found out that Mesenchymal stem cells are right stem cells for the treatment as they act as a natural and healthy protection from kidney damage. HSCI have found out that Mesenchymal stem cells contain “protein candidates secreted from mesenchymal stem cells that may be administered independently to aid in kidney repair. Mesenchymal stem cells are being incorporated into miniature dialysis machines that expose the patient’s blood to these cells, allowing pro-repair proteins to be delivered directly to the kidneys” (‘Kidney Disease’).

Since this is a new treatment, still being developed and investigated, there have been no surgeries for mesenchymal stem cells being removed and transportation to the kidneys to help cure chronic kidney disease. So far there have been only clinical trials that have been allowed and done. For the treatment to take place, first the mesenchymal stem cells are extracted and collected from the bone marrow spaces or from the pelvic bones to later be prepared for injecting. Many punctures are made along the bone, which helps the blunt send needle to collect the cells. The procedure is called bone marrow harvesting and takes 2 to 3 hours at 1 sitting. After the stem cells are extracted, it is later taken to the laboratory to get separated from the blood. The blood is either separated in a laboratory and later injected back into the patient or the blood is directly separated by a machine, while the doctors are performing the bone marrow harvesting. The machine that is used to separate the stem cells from the blood is called an apheresis machine. Finally, the implantation procedure is completed when the collected stem cells are injected into the kidneys, which after days or weeks will help repair damaged nephrons and regain the kidneys functions.

No Stem Cells, Dialysis

Since the treatment of mesenchymal stem cells for CKD has not been tested on an actual human patient, it is an ongoing investigation and a solution, a treatment and a cure for the future. This technology is a future treatment which is still being tested. So far only clinical trials and tests have occurred, where the tests and treatment are used animals. A clinical practice that took place in Villanueva (Philippines) stated that 6 patients offered to perform the investigation and treatment on them. They injected a certain dose to each of these patients who had CKD. This amount of dose was used in previous studies which turned out to have an impact on the subjects. These patients had different causes of CKD, which was used to predict and find out if the therapy could work on any type of patient. A website states that “All patients were medicated, including administering of renin-angiotensin blockade, before enrollment and during the study.” (“Use of Mesenchymal Stem Cells for Chronic Kidney Disease”). As an end result of the study there was no end result, no unpropitious seen in any of the patients, and this continued over a period of 1 year. The doctors later found out that there were specific improvements seen in the urinary protein excretion.

Until the stems cells is further developed and can be trusted, the only alternative treatment is dialysis. Dialysis is needed when a patient is in a critical condition due to his/ her kidney. This treatment is done using a machine called the dialysis machine or an apheresis machine. This machine helps filter the patients’ blood by itself as the body cannot. This machine helps remove waste, salt and extra water from the body to prevent the waste filling the body. It also helps maintain a certain level of chemicals in your blood and helps control blood pressure. Dialysis can be done at the hospital, clinic home, all based on the doctors and patient’s needs.

Technology’s Potential Global, Economic and Social life, Effect

This new developing technology helps and effects globally, economically and socially both negatively and positively. Dialysis and transplantation take up both time and money. This new technology has helped the patient’s social life as it prevents them from driving to the hospital or clinic to continue their dialysis. The cost of these types of treatments are $80,000 per patient. Dialysis takes up both the patient’s social life and their money, when the new technology will reduce that. A kidney transplant costs the same as 2 dialysis treatments and also takes up 2 – 3 years approximately for the patient to find an available donor. A transplantation can also result to a back clash, when the body reacts to a new and unknown organ. Kidney transplant too, take up the patients economic and social life. The treatment of mesenchymal stem cells for CKD will in the future help maintain all this. Although the price is not verified, it is said to take up only a few days to weeks of the patient’s life, later resulting an improvement. Chronic kidney disease has impacted globally but this new treatment will prevent this. This treatment will affect the patient’s life a bit negatively at first due to the new cells and the bone marrow harvest process.

Technology and the Body Systems

The technology, mesenchymal stem cells for CKD will help cure and treat the kidney, affecting the urinary system. Mesenchymal stem cells will help stop the buildup of waste and fluid in the bladder. I will help regain the kidneys function of filtering and remove the remaining waste through the urethra. If mesenchymal stem cells or any stem cells found good for the treatment is injected it will help cure the kidneys and help fight further diseases and infections.

Stems Cells and Other Implications

Today, in the 21st century, stem cells are 1 of the newest and most profited treatment. Studies over the past decades have found that the cells located in the bone marrow can be used and studied for many other implications and diseases. Stem cell therapy has been used to:

• Treat certain blood groups, who have a lack of red blood cells and etc.
• Help treat immune system disorders
• Rebuild the red blood cells if needed
• Help treat and fight some cancers
• They mainly help regrow and replace damaged or lost cells into the circulatory system and around the body.
• And finally, they are used to treat common diseases such as leukemia, lymphoma and so on.

REFERENCES

1. Newman, Tim, and CPN Carissa Stephens. ‘Chronic Kidney Disease: Symptoms, Causes, And Treatment’. Medical News Today, 2019, https://www.medicalnewstoday.com/articles/172179.php.
2. Information, Health et al. ‘What Is Chronic Kidney Disease? | NIDDK’. National Institute Of Diabetes And Digestive And Kidney Diseases, 2019, https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/what-is-chronic-kidney-disease.
3. ‘High Blood Pressure and Chronic Kidney Disease’. Kidney.Org, 2019, https://www.kidney.org/sites/default/files/docs/hbpandckd.pdf.
4. Information, Health et al. ‘Causes of Chronic Kidney Disease | NIDDK’. National Institute Of Diabetes And Digestive And Kidney Diseases, 2019, https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/causes.
5. ‘Facts About Chronic Kidney Disease’. National Kidney Foundation, 2019, https://www.kidney.org/atoz/content/about-chronic-kidney-disease.
6. Information, Health et al. ‘Kidney Disease Statistics for The United States | NIDDK’. National Institute Of Diabetes And Digestive And Kidney Diseases, 2019, https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease.
7. Nawras, Allie et al. ‘Advances in Kidney Treatment: Looking at The Potential of Stem Cells’. Pharmaceutical-Technology.Com, 2019, https://www.pharmaceutical-technology.com/news/advances-in-kidney-disease-and-treatment-stem-cells/.
8. ‘Kidney Disease’. Hsci.Harvard.Edu, 2019, https://hsci.harvard.edu/kidney-disease-0.
9. ‘How Stem Cell Therapy Could Replace Tommy John Surgery to Repair Muscles’. Los Angeles Times, 2019, https://www.latimes.com/sports/la-sp-g-angels-stem-cell-20160628-snap-htmlstory.html.
10. transplantation, Harvesting. ‘Harvesting Blood Stem Cells For Transplantation’. Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/books/NBK279428/.
11. ‘Chronic Renal Failure (Kidney Failure) Information | Myvmc’. Healthengine Blog, 2019, https://healthengine.com.au/info/kidney-disease-chronic-renal-failure.
12. ‘11.3 The Kidney | Bioninja’. Old-Ib.Bioninja.Com.Au, 2019, http://www.old-ib.bioninja.com.au/higher-level/topic-11-human-health-and/113-the-kidney.html.
13. Chung, Byung Ha. “Use of Mesenchymal Stem Cells for Chronic Kidney Disease.” Kidney Research and Clinical Practice, Korean Society of Nephrology, 30 June 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC6577207/.
14. ‘What Is Dialysis?’. National Kidney Foundation, 2019, https://www.kidney.org/atoz/content/dialysisinfo.
15. “Urinary System.” Study.com, Study.com, study.com/academy/lesson/major-types-of-urinary-system-diseases-disorders.html.

Introduction

As the name suggests, polycystic kidney disease (PKD) is a condition characterized by the formation and growth of cysts in the kidney. This disease is a genetic disorder with two different types. The first is autosomal dominant polycystic kidney disease (ADPKD) and is the more common of the two. The second type is autosomal recessive polycystic kidney disease (ARPKD), which is much rarer (Crow, 2017). Being a genetic disorder, PKD can be assumed to have existed throughout human history. However, it was encountered and observed medically in 1586, with the death of the King of Poland, Stephen Bathory. After his death, his Surgeon Jan Zigulitz recorded that the king’s kidneys were large as a bull, with a bumpy and uneven surface. In the 18th century, doctors and historians reading these records concluded that PKD must have been the cause of his death. The term “polycystic kidney” was first used in 1888 by Flix Lejars, who characterized the disease as affecting both kidneys, and having clear and specific symptoms. In 1994, the disease was discovered to have a cause that was genetic in nature, with around 85% of ADPKD patients possessing the PKD-1 gene on chromosome 16 (Balat, 2016).

ADPKD affects around 4.3 per 10,000 people, or 0.043% of the population. It is almost twice as likely for women to be diagnosed in early adulthood because of their receiving of ultrasound testing during childbearing years. On the other hand, males are commonly diagnosed at the 65 years and older demographic, indicating that there is greater possibility for ADPKD to be undiagnosed in young men. In the United States, ADPKD affects about 140,000 patients, making it a relatively rare disease. On the other hand, ARPKD affects 1 in 20,000 to 40,000 people (Willey et al., 2019).

PKD will not cause signs or symptoms while the cysts are small. Thus, PKD will be difficult to detect without being tested. Once the cysts are 0.5 inches or larger, symptoms will begin to manifest themselves. Symptoms include high blood pressure, blood in urine, excessive urination, headaches, and pain in the abdominal area or in the back. Furthermore, this condition will lead to the formation of clusters of cysts in the kidney and potentially other organs like the liver, pancreas, and testes. PKD is also associated with aneurysms in the arteries or the brain, and diverticula of the colon (Phillips, 2018).

Generally, the only risk factor for this disease is having inherited this gene from one’s parents or grandparents. However, it is possible for this disease to occur without parents carrying the mutation due to a mutation occurring in the embryonic development process. (Iliuta et al., 2017)

Pathophysiology

PKD is an inherited disease that is caused by mutations occurring in the genes, that have been inherited from one’s parents. In ADPKD, 85% of cases have the mutation occurring in the PKD1 gene, located on chromosome 16p13.3. In the remaining 15% of cases, the mutation occurs in the PKD2 gene, located on chromosome 4q21-23. The PKD1 gene codes for the protein polycystin-1 (Igarashi & Somlo, 2002). This protein contains a long extracellular N-terminal portion and eleven transmembrane domains. The extracellular portion contains multiple domains, including two leucine-rich repeat areas, that are able to bind collagen, fibronectin, and laminin. The protein also may be able to bind carbohydrates and the protein-ligand. The PKD2 gene codes for the protein polycystin-2. In ADPKD, all the cells in the kidney carry the mutated gene, but only some of the nephrons (the kidney’s functional subunit) present cysts, with each nephron having a few cysts. Thus, ADPKD is a focal disease that does not impact all of the kidney’s nephrons equally (Walker, Mojares, & Hernández, 2018).

While the exact mechanism of cyst formation is not understood, the focal nature of the disease has caused researchers to suggest a two-hit model (Qian et al., 1996). This model begins with the assumption that an individual with ADPKD has inherited a mutated PDK1 or PDK2 gene from one parent, and a wild-type gene from the other parent. The model theorizes that the wild-type gene then becomes inactivated during the individual’s lifetime, due to a somatic mutation. These somatic mutations are mutations that happen in adult fully formed cells when are then passed on to successive generations of cells. As somatic mutations happen infrequently, the formation of cysts will also be irregular, and only localized to specific nephrons in the kidney. This theory is supported by studies showing that renal cysts have lost their wild-type allele and are no longer heterozygous. If this theory is true, then it must also account for the large number of cysts that exist in the later stages of polycystic kidneys. This can be accounted for by studies observing the rate of somatic mutations in kidney epithelial cells is ten times higher than the rate in other cells (Colgin et al., 2002).

While the reason for the difference in mutation rate is unknown, it does explain how the high incidence of mutation could be possible. Polycystin-1, the product of the PK1 gene, is a protein that regulates the cell cycle, and the unregulated proliferation of the cell may be one factor leading to vesicle fusion, and eventually cyst formation. Polycystin-2, the product of the PK2 gene, protein that functions as an intracellular calcium release channel (González-Perrett et al., 2001). The mutation in the calcium channel causes the rise of calcium in the cytosol, which can lead to vesicle fusion and changes in the transcription of genes, and eventually cyst formation. Although the products of the PK1 and PK2 genes are different, the fact that they interact in the same pathway gives an explanation for why they both result in the same result of cyst formation (Qian et al., 1996).

The presence of cysts in PKD hinders the kidneys from their function of filtering waste products in the blood. While each cyst itself is not tremendously dangerous, the high number of steadily growing cysts harms the body by impacting the kidneys at a mechanical level. This can lead to high blood pressure, blood in the urine, and pain in the kidney area felt as emanating from the back or sides. Compared to a healthy kidney, a polycystic kidney will be enlarged, riddled with up to thousands of cysts, and severely lacking in function. PDK can also be accompanied by cysts in the liver, or other organs (‘Kidney Cyst | Polycystic Kidney Disease’, 2019).

Treatment and Research

There is currently no cure for autosomal dominant polycystic kidney disease (ADPKD), and it is not possible to stop cysts forming in the kidneys for those who have been diagnosed with the disease. However, as ADPKD progresses slowly, there is a window of opportunity to treat the disease by retarding cystic expansion. On Tuesday, April 24, 2018, the U.S. Food and Drug Administration granted approval of tolvaptan for ADPKD treatment, the first medication of its kind for this disease. This medication has also received a recommendation from the National Institute for Health and Care Excellence for ADPKD treatment (‘Approved as First Treatment for ADPKD’). Tolvaptan interacts with arginine vasopressin, a hormone that promotes the reabsorption of water from the fluid in the kidney’s tubules into the collecting duct. Tolvaptan is an arginine vasopressin antagonist, hindering this hormone’s ability to function. The precise mechanism is to block vasopressin-2 receptors in the collecting duct of the kidney. In doing this, it increases the excretion of free water while maintaining the kidney’s functionality. The result is that the formation of cysts in the kidney is slowed (Bhatt et al., 2014). By reducing the rate of cyst growth, tolvaptan reduces ADPKD’s kidney growth and enables longer preservation of kidney function. However, tolvaptan is only available to adults who have chronic kidney disease (at stage 3 or 4) at the start of their treatment, when there evidence of rapidly progressing kidney disease. Tolvaptan is given as a tablet, which is taken twice per day. The side effects of tolvaptan are primarily related to the frequency of urination. Thus, tolvaptan causes side effects like thirst, the urination of at least 3 liters per day (polyuria), and the need to pee more than 5 times at daytime (pollakiuria) and once at night (nocturia). Another more severe negative side effect of tolvaptan is chemical-related liver damage (hepatotoxicity), which has also been reported in a number of patients. Thus, taking tolvaptan must be accompanied by frequent monitoring (‘Treatment: Autosomal dominant polycystic kidney disease’, 2019).

Prior to the availability of tolvaptan as a means of treatment, treatment involved seeking to address the various health complications arising from ADPKD. For example, ADPKD can lead to high blood pressure, kidney stones, and localized pain. While ADPKD itself could not be treated, treatment focused on addressing these symptoms. Of these symptoms, hypertension is the most common. ADPKD can also lead to the experience of back or side pain due to the enlargement of the kidneys, or pain due to kidney stones. In these cases, the practice is to avoid the use of ibuprofen and other non-steroidal anti-inflammatory drugs. This is because such drugs can raise one’s blood pressure, and work against the drugs being taken to reduce blood pressure. Instead, painkiller drugs like paracetamol, codeine, or tramadol are given. Chronic pain can also be treated with the use of antidepressants. In terms of surgical treatment, large cysts can be drained in order to release pain from pressure and reduce kidney enlargement (‘Treatment: Autosomal dominant polycystic kidney disease’, 2019).

As the disease progresses, the patient’s kidney functionality will be regularly observed. As the kidneys approach kidney failure, the patient has two options of treatment. The first option is to regularly give them dialysis, which is the process in which a machine replicates some of your kidneys’ functions, filtering the body’s blood. Dialysis generally is administered in four-hour sessions, three times a week. The other option of treatment is to receive a kidney transplant, which is the removal of the diseased kidney and the implantation of a healthy donated kidney. For implanted kidneys, as they do not share the genetic phenotype of the ADPKD/ARPKD individual, they do not develop cysts. These transplants can come from either deceased donors, or from a donated kidney, possibly from a blood relative. Receiving a kidney transplant dramatically increases the quality of life that a PKD individual will experience when compared to having to receive regular dialysis (‘Treatment: Autosomal dominant polycystic kidney disease’, 2019).

Article Critique

The article chosen for this assignment is “Genetics and Pathogenesis of Polycystic Kidney Disease” by Peter Igarashi and Stefan Somlo, published in the Journal of American Society of Nephrology. This article is excellent in its comprehensive nature, as it explains the disease in. The article begins with a general explanation of PKD as a disease and the nature of the cysts that are formed in the kidney. It also provides a concise explanation of the genetic nature of this disease and the dominant and recessive forms that it takes. Overall, the beginning of the article is accessible enough for anyone unfamiliar with this disease to get a basic grasp of the disease, its genesis, and its symptoms.

This article is also strong in its clarity. Although it addresses a potentially complex topic, its accessibility is increased in that it takes a logical progression that increases in complexity. After a simple intro, it explores the genetics of the disease. It then describes the focal nature of the disease and presents a two-hit model of how cysts are formed. It gives the confirmation of this hypothesis in mice models. The article then progresses into a more complex and technical portion, exploring the disease at the gene and protein interaction level. It does this for the ADPKD specifics of the disease and then begins to address the detailed interactions for the ARPKD expressive of the disease. In the latter portion of the article, it addresses the involvement of cilia in PDK. Another strength of this article is that it seeks to give as much explanation of the disease at the protein level, despite the fact that much of the details of PKD are unknown. This article closes with the presentation of cilia as a potential target of treatment, which is a helpful but brief conclusion.

One of the weaknesses of this article is that it is dated. Being published in 2002, there has been much development in the science of PKD, especially the development of tolvaptan as treatment, and its FDA approval in 2016. Thus, this article is an excellent resource in understanding the disease and its underlying causes and protein interactions. However, in order to gain an understanding of the current science of this disease, this article should be complemented with articles from the past five years.

“The past is the experience, the present is the experiment, and the future is the expectation. So invest the experience in the experiment to meet the expectations.” – Unknown

The “Experience”

Dr Thomas Graham, a 19th- century chemist whose scientific work on osmotic forces of fluids paved the way to the present form of blood purification techniques and coined the term ―dialysis‖. In 1913, Dr John Jacob Abel, an American pharmacologist and biochemist attempted dialysis in vivo. Although his attempts were futile in human trials, his machine was dubbed as the ―artificial kidney‖. In 1945, Dr Willem Johan Kolff, a Dutch scientist, who is recognised as the ―Father of artificial organs‖ was the first to perform the successful hemodialysis (HD) on a patient with acute kidney injury (AKI). He used cellophane as the membrane (connected to the circulation) immersed in a drum pool of dialysate (saline solution) and removed 60 grams of urea over 11.5 hours, and called it the ―rotating drum kidney‖ (1). In 1973, with significant advances in vascular access for dialysis and political reforms to include dialysis under Medicare coverage, maintenance HD became a reality for chronic kidney disease (CKD) patients (2). Peritoneal dialysis (PD) remained a treatment for AKI, until Tenckhoff described the use of silicone-rubber-based permanent indwelling catheter in 1976. Over the last five decades, undoubtedly, dialysis has saved millions of lives worldwide, and the field is in a continuous process of evolution (3).

The United States Renal Data System (USRDS 2016) has estimated an annual cost of over $30 billion for treatment of End-stage renal disease (ESRD), of which the most common treatment modality is HD (87.7%) but fails to restore full health. Although Kidney transplant (2.5%) with overall low cost, more prolonged survival and better quality of life is the best form of renal replacement therapy (RRT) at present, the procedure is limited by non-availability of donors worldwide, and the remaining patients are maintained on PD (9.6% ).

Most of the CKD patients are treated with in-centre intermittent HD (conventional HD), which is given three times a week, each session lasting for 4 hours, resulting in excess water removal and less solute removal. Moreover, the time and cost spent on travelling to the dialysis centre, the need for workforce, electricity and disposables (120-140 litres of dialysate per session) are significant drawbacks. Also, these patients have to be on dietary restrictions, and limitation of movements during HD sessions significantly impairs the quality of life. Although PD provides a form of RRT outside a hospital setting, the level of blood purification is relatively low and overtime, the functionality of peritoneal membrane decreases due to toxic effects of high glucose concentration in PD solutions and recurrent infections of the peritoneal membrane. In North America, the reported mortality rate is 5% to 10% for patients in the waiting list for renal transplants, and within ten years around 40% of patients lose their graft function or die post-renal transplant with average long term graft longevity of 12 years (4).

The most common form of RRT at present is conventional HD that relies on solute removal for blood purification by diffusion, convection and adsorption, either used in isolation or in combination (5). PD uses diffusion and convective methodology to transport and regulate solute movements. A high concentration of glucose is required in the PD fluid to

facilitate ultrafiltration. The solutes can be divided according to their molecular weight (MW) into low (15000Da). Traditionally, the effective clearance of urea by hemodialysis is based on the KT/V model (K = Urea clearance, T = per unit time and V= total body water). Sufficient clearance is achieved when weekly KT/V is ≥ 1.2 for conventional HD and ≥ 2 for PD. The middle molecules (β2-microglobulin, parathyroid hormones) and large MW protein-bound toxins are not efficiently cleared by conventional HD. Serum β2-microglobulin level is often used as a surrogate marker of these middle molecule clearance in HD setting. Most studies have shown ineffective removal of middle and large MW toxins leading to dialysis-related amyloidosis, and increased prevalence of cardiovascular diseases in CKD patients (6).

Many studies have proven that daily extended dialysis provides better quality of life, improved blood pressure control, reduction to no use of phosphate binders, improved bone mineral metabolism and enhanced clearance of middle molecules. The slower solute and fluid removal prevents frequent episodes of intradialytic hypotension, leading to regressed myocardial stunning (7).

All the factors mentioned above demand a change in the current clinical practice to achieve a better clinical outcome in CKD patients by prolonging the longevity, improving the quality of life and decreasing the number of the donor to recipient ratio mismatch. Developments in the field of nanotechnology, sorbent systems and cell culture techniques show a promise to achieve these goals.

The “Experiment”

The ideal alternative therapy for CKD patients should constitute ―3Cs‖ and ―3Rs‖, viz Cost-effectiveness, Convenience (better quality of life) and provide Clearance and at the same time be Reliable (easy monitoring), have Reduction in size, expense and number of disposables, and aid Relocation of patients to home from a health care facility. Among the many concept models on the field of artificial kidneys, only a few innovations are in advanced stages of research. The four main devices that are in the verge of breakthrough that meet the above criteria are the wearable artificial kidney (WAK), automated wearable artificial kidneys (AWAK), implantable artificial kidney (IAK) and the renal assist device (RAD).

WAK:

The WAK is a blood-based renal replacement system that weighs < 5kg with a battery-operated belt type model. This system uses regenerated dialysate using advanced sorbent technology. The system is connected to a double lumen HD catheter using 0.45% sodium chloride solution as a primer. The blood is initially anticoagulated through a heparin syringe pump. The anticoagulated blood and dialysate propel into a polysulfone- based hollow fibre dialyser. The pulsating blood pump uses a pull and push pattern, alternating such that the dialysate compartment is at the peak flow when the blood flow is at trough, and vice versa resulting in effective clearance of solutes. The purified blood then goes through a gas bubble detector chamber before being returned to the patient. The ultrafiltrate is controlled by a pump mechanism which diverts a portion of regenerated dialysate into a waste bag. It has a safety mechanism to stop ultrafiltration if the blood flow is halted (8).

WAK and AWAK use advanced sorbent technology, which is the first or second generation REcirculation DialYsis (REDY) sorbent system which contains several layers.

The spent dialysate is passed into a chamber containing activated charcoal for removal of non-urea organic compounds. The next column contains enzyme urease which hydrolysis urea into ammonia and carbon dioxide. On hydration with water molecules, hydrogen ions from the water molecule convert ammonia into ammonium and carbon dioxide is converted to bicarbonate and hydroxide. Subsequently, the zirconium phosphate ion layer, exchanges hydrogen or sodium ions for the spent dialysate containing potassium, magnesium and calcium. Similarly, the ammonium produced is bound by negative charge and removed from the spent dialysate. Finally, zirconium carbonate and zirconium oxide adsorb phosphate and releases bicarbonate, hydroxide and acetate (9).

In 2007, Davenport et al. conducted the first pilot study on eight patients using WAK over 4 to 8 hours which showed promising safety and efficacy of WAK model (10). Following this, Gura et al. conducted a Food and Drug Administration (FDA) approved human trial of WAK on seven patients over 24 hours and reported a mean clearance of the middle molecule β2-microglobulin (5±4ml/min), phosphate (15±9 ml/min), urea (17±10ml/min), creatinine (16±8 ml/min) and 24-hour ultrafiltration (1002±280 ml). Though the initial trial included ten patients, the trial was stopped after the seventh patient due to technical problems of excess gas bubble formation, kinking of the tube and variable pump function. Five out of the seven patients completed the study (one subject had clotting of blood circuit following ambulation, and the others were discontinued owing to pinkish discolouration of dialysate, suspicious of hemolysis). The data suggests an adequate clearance of middle molecule, maintenance of electrolyte and fluid balance, and better quality of life (11).

The WAK has its advantage of being light-weighted, requiring around 400mL of dialysate, ergonomic to be worn as a belt, no dietary restriction, allowing the patient to ambulate and better quality of life with improved solute clearance and decreased side effects. The inclusion of biofeedback controller system in WAK to monitor blood, biochemical and thermal changes help in achieving the target treatment dose and avoids any hazardous intradialytic events (12).

The disadvantages of WAK include the technical challenge of vascular access as current vascular options have a high risk of bleeding with the use of anticoagulants and are prone to accidental disconnections (13). The long term vascular catheters are advocated rather than needles to prevent dislodgement. However, the risk of long term indwelling

vascular catheter-related infections and consequences of continuous use is not well defined. Secondly, if premature saturation of zirconium phosphate ion-exchange channel occurs, the ammonium may breakthrough into the dialysate and thus into the patient causing more toxic effects. The breakdown of urea releases carbon dioxide gas, which may inadvertently pressurise the space of dialysate, causing mechanical system failure and reduced ultrafiltration (14).

AWAK:

AWAK, also known as WAK-PD, is a tidal peritoneal dialysis based artificial kidney model currently under human trials. AWAK regenerates dialysate to minimise fluid requirements. The AWAK consists of a miniaturised disposable module (storage and enrichment compartment, sorbent cartridge and tubing set for ultrafiltrate) which is encased in a durable module containing the batteries and controller pumps. Similar to conventional PD, a reserve volume of 1.5 litres of dialysate is instilled into the peritoneal cavity which absorbs waste products, toxins and fluid through the peritoneal membrane. In the WAK-PD, an equilibrated dialysate tidal volume of 500mL is drained from the patient and passed through the storage system and pumped through the sorbents for removal of toxins. The dialysate is then filtered and supplemented with a prescribed amount of glucose and returned to the peritoneal cavity. Each tidal exchange takes about 7.5 minutes, providing an average flow of 96 litres of regenerated dialysate per day. The reserve volume of dialysate is circulated back into the peritoneal cavity, and the ultrafiltrate is drained into a collection bag which is discarded along with the disposable module every 7 hours.

The advantages of AWAK include bloodless, easily portable miniaturised device weighing < 2kg, which can be worn like a purse. The dialysate requirement is only 2 L/day compared to 12 L/day in conventional PD, leading to a decreased risk of herniation, abdominal pain and distension. The weekly clearance of urea estimated by KT/V model using AWAK was much above than that of conventional PD. A study using AWAK for 4 to 24 hours in 20 male patients showed an average urea clearance of 31.4mL/min and improved phosphate and middle molecule clearance which is better than conventional PD (15).

Similar to WAK, gas bubble formation leading to mechanical failure is seen in AWAK, and this issue is being addressed in the second generation modules by the inclusion of a degassing unit similar to the ones used in WAK systems. The sorbent cartridge (disposable module) has to be replaced every 7 hours requiring storage of multiple sorbent cartridges in both AWAK and WAK models. The risk of peritoneal sclerosis, hyperglycaemia and membrane failure following a regenerated dialysate is not well known at this time.

The Vicenza Wearable artificial kidney (ViWAK):

ViWAK is similar to AWAK with an additional concept of a computer-based handheld remote. However, the device has not reached clinical trials and requires an addition of an injection system to infuse glucose and bicarbonate (16).

IAK:

The IAK currently under preclinical study weighs less than 500g, incorporates tissue engineering and silicon nanotechnology into a device which can mimic a native kidney following surgical implantation. The device consists of a HemoCartridge (high flux and high selective filter) with a BioCartridge (bioreactor of culture renal tubular cells). Following implantation similar to renal transplant, the ultrafiltrate from the HemoCartridge is processed by the BioCartridge which returns essential water, glucose and salt back into the blood and concentrates a small volume of toxic fluid similar to urine which is drained into the bladder.

The device functions with patients own blood pressure alleviating the need for blood pumps and non-requirement of dialysate. The blood conduits are engineered to prevent stagnation of blood and shear stress avoiding the need for anticoagulation in animal models, and no immunosuppressant drugs are needed as the BioCartridge scaffolds serve as a barrier preventing cellular and molecular effectors from interacting with tubule cells. Thus, avoiding the activation of patient’s acquired and innate immunity.

The disadvantages include frequent monitoring of electrolytes and hydration to replenish the extracellular fluid volume and restriction of diet. No data is available regarding the longevity of the device and the need for additional surgeries to replace the equipment. The ―culture stress‖ where the mammalian cells undergo erosion of fundamental phenotypic properties was seen in the animal models (17).

Stem cell therapy and Bioartificial kidneys:

Stem cell therapy uses the glomerular microarchitecture, and vascular mechanical properties of extracellular matrix (ECM) from discarded human kidneys to provide a decellularized kidney scaffold using various solution strategies. These scaffolds may later be used for cellular regeneration using embryonic stem cells (ESCs), human inducible pluripotent stem cells (iPSCs), human amniotic stem cells (HASCs) and human renal cortical tubular epithelial cells (RCTEs) injected either through the intravenous route, subcapsular or cortical injections. Ross et al. have successfully re-cellularized a kidney scaffold using ESC in a mice model which may hold promise for kidney regeneration using natural scaffolds in the future. However, till date, a standardised protocol for decellularization and recellularization technique has not been accepted (18).

The bioartificial hybrid kidney is also known as the Renal assist device (RAD) comprises an active renal tubular cell reactor and a passive hemofilter, which is designed to mimic the secretive and reabsorptive functions of nephron tubule. RAD has completed phase II clinical trials on patients with acute kidney injury (AKI) and multiorgan dysfunction syndrome, which showed excellent safety and absolute risk reduction of 20% and a 40% relative risk reduction in mortality. These results show a tri-fold improvement in the treatment of sepsis compared to other recent pharmacologic trials in AKI setting.

Though RAD requires an extracorporeal circuit with peristaltic pumps to provide the driving force and lacks consistent cell sources for production, it has its advantage of being dialysate-free and offers the metabolic and endocrine function to some extent which other dialysis strategies do not provide (19). In future, cell sourcing issues for RAD may be addressed with the development of Bioartificial Renal Epithelial Cell System (BRECS) which cultures and cryopreserves the renal epithelial cells (20).

The devices mentioned above though under preclinical and clinical research stages have a distinct advantage of being free of wired electricity, least requirement of dialysate, decreasing the stress on the family and generating less waste than conventional HD. These devices show significantly improved clearance than presently available options, better indexes of bone mineral metabolism, reduced incidence of ultrafiltration mediated hypotension and most important of all improving the quality of life.

The cost information is not available for any of these devices at present. However, with an increase in the number of patients preferring these advanced options, the health care burden for treatment of ESRD would be significantly reduced.

THE “Expectation”

The Advancing American Kidney Health (AAKH) initiative was launched in July 2019 with a tri-pronged strategy to reduce the number of CKD patients, to increase the use of home dialysis and increase the number of renal transplants. This initiative also encourages and acknowledges the developments in the field of artificial kidneys. The AAKH through the KidneyX (the Kidney Innovation Accelerator) foundation provides funding for the new technologies of ESRD. Similarly, the FDA’s Center for Devices and Radiologic Health (CDRH) has initiated a competitive program to encourage innovations in the field of ESRD (21).

The Debiotech of Switzerland, Dutch kidney foundation (Neokidney development program) and AWAK technologies of Singapore collaborated in 2017 to develop a portable artificial kidney that would be cost-effective and ergonomic, enabling frequent and more prolonged home dialysis (22).

In conclusion, a combination of new technology integrated with continuous follow- up involving a multidisciplinary team of clinical researchers, engineers, social scientists and economists is required to realise the dream of revolutionising the treatment of CKD.