New and Upcoming Treatments for Polycystic Kidney Disease.

ID#: 861 Description: Gross pathology of polycystic kidneys. Gross pathology of polycystic kidneys. Ureters are visible. Content Providers(s): CDC/Dr. Edwin P. Ewing, Jr. Creation Date: 1972 Copyright Restrictions: None - This image is in the public domain and thus free of any copyright restrictions. As a matter of courtesy we request that the content provider be credited and notified in any public or private usage of this image. (Photo credit: Wikipedia)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease of the kidney. For many years the treatment of this condition has been at a relative standstill when compared to the advances in therapy in other kidney diseases. However exciting new developments are currently in the research pipeline. These may finally allow specific therapies aimed at reducing the progression of the underlying problem, which has always been the unrestricted almost exponential growth of cysts within the kidney leading to kidney failure.

The main approach to the treatment of autosomal dominant polycystic kidney disease has been good control of blood pressure. This has been shown to reduce the rate of progression of the disease to end stage. Patients with ADPKD have been shown to have elevated levels of a hormone known as renin. Renin is important in regulating the balance of fluid and salts within the body and under normal circumstances renin signals the kidney to retain salt and water in order to maintain a normal volume of blood within the body. In ADPKD renin levels are increased, this may be due to the compression of sensitive areas within the kidney by enlarging cysts, compression of these areas may stimulate the production of renin. Renin and other substances directly produced because of high levels of renin result in increased cyst growth in ADPKD. This produces a viscous cycle of events that leads to ESRD.

Aliskerin is a novel drug which is now available, it functions as an inhibitor of renin. This drug has been shown to significantly lower the levels of renin in patients with ADPKD as well as providing better control of hypertension. This may be become a mainstay of the treatment of hypertension in ADPKD and should definitely be a drug to watch.

A very old drug that has been hypothesized to have a preventative role in ADPKD is colchicine. It is better known for its role in the management of gout. It is a potent anti inflammatory agent and has effects which may be useful in delaying cyst growth.

Cyst growth in ADPKD is based on the accumulation of fluids within the cyst by the action of a complex pump known as CFTR which is the same protein which is abnormal in cystic fibrosis. Inhibtors of CFTR have been available for some time. Recently they have been shown to be of efficacy in reducing cyst growth in mouse models of APKD.

The drug sirolimus which has been used for many years for immunosuppression post renal transplant has been shown in mammalian models of ADPKD to reduce the growth of cysts and is now the target of a study which will determine its role in the treatment of ADPKD in humans. The results of this study will be available in 2010.

Deutsch: Schema der beiden Proteine PKD1 und PKD2. Nach einer Vorlage von http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2003/MaloneyH/Polycystins.html (Photo credit: Wikipedia)

The focus thus far has been on possible therapies aimed at reducing the growth of cysts in order to reduce progression to ESRD. However other new therapies are available currently for the treatment of symptoms associated with ADPKD such as recurrent hematuria and pain.

Techniques aimed at reducing the number of existing cysts in the kidney have been shown to reduce symptoms. Options for this kind of therapy range from open surgery with direct decompression and decortication of cysts, laparoscopic procedures to reduce cyst volume and more recently ultrasound guided techniques where substances that destroy the structure of the cysts are injected under guidance. All these techniques have been proved beneficial in terms of symptom relief but have not been shown to delay progression of the kidney disease.

That  particular goal remains elusive but we are closer now than ever before.


photo credit: euthman

Rituximab and FSGS.

Intermed. mag. Image: Focal segmental glomerulosclerosis - high mag.jpg (Photo credit: Wikipedia)

FSGS or focal and segmental glomerulosclerosis is the most common non diabetic cause of nephrotic syndrome in the world. This is particularly true among African Americans. The treatment of this disorder is frequently complicated by non response to the primary modality of treatment which is steroids. Combine this with the need for high doses to produce an effect, the known toxicity of steroids and we begin to see there is need for a better drug. Unfortunately many of the drugs attempted are also toxic or produce a situation of dependence where the disease may go into remission but it quickly relapses when the drug is discontinued. Rituximab is a drug that has had some success in lupus nephritis and now it is undergoing trials in patients with FSGS. The current study by investigators from spain, looked at a small cohort of 8 patients and found that rituximab was effective only in the minority of patients, only 3 patients had a favourable response to the drug. It is however interesting that in at least one patient that responded there was a durable massive reduction in proteinuria. The fact that this occurred should inspire some hope that the drug may be useful if an effective regimen capable of benefiting more patients can be elucidated.

Related articles

• Steroids and Kidney Disease (allkidney.com)
• New Treatments For FSGS -ASN Conference (allkidney.com)

Patient Education: What is the best form of dialysis.

Dialysis USA 3-2007 004 (Photo credit: jimforest)

This question is asked more times than can be counted. A patient is informed that they have stage 4 kidney disease and they need to make a choice as to what modality of dialysis they prefer while they await transplantation.

The patient is usually confused and unsure, already overwhelmed with dealing with the reality of having to receive organ replacement therapy in the first place. Usually the decision is made without enough information and reflects the personal bias of the physician with whom the patient has the most trust.

Rarely will a patient have a preconceived idea as to what form of dialysis would best fit their lifestyle and rarely still does one find a busy nephrologist with the patience to explain in the detail the pros and cons of all modalities without introducing personal and professional preference.

If we were to take a moment to answer this question we would realize that thinking about the answer in a vacuum without a patient involved is difficult. It is difficult because there are patient specific factors which influence the modality of choice. Therefore the best way would be to examine the pro's and cons of each separate modality, giving the patient the power of choice empowered by knowledge.

The most established modality is haemodialysis dating back to 1945, physicians therefore have a great deal of experience with this modality it has stood the test of time and advanced rapidly with greater understanding of the processes of diffusion and osmosis as well as the development of plastics. Understanding the complex equations which determine membrane transport characteristics and hence dialysis adequacy are a badge of pride for nephrologists.

Peritoneal dialysis could be considered to be the older dialysis modality. It was first attempted in humans in 1923 and was partially successful. Between 1923 and 1928 surgeons performed several procedures which prolonged the life of patients using peritoneal dialysis, however adoption of this method was slow and to some extent marginalized during the development of haemodialysis.

Modern haemodialysis and peritoneal dialysis can be considered equal means of renal replacement therapy they each have their strengths and weaknesses.

HAEMODIALYSIS

http://www.flickr.com/photos/nomadicentrepreneur/ / CC BY-NC 2.0

Pros

• Treatment is rapidly effective at clearing toxins from the blood stream.

• Dialysis adequacy can be increased easily to match the needs of the patient.

• Treatment failure and withdrawl from haemodialysis is less common.

Cons

• Dialysis occurs across an artificial membrane which may cause allergic reactions.

• Blood stream access is necessary and most be maintained.

• Haemodialysis is expensive

• Low blood pressure occurs during haemodialysis more frequently

• Higher risk of bleeding due to the use of blood thinners like heparin.

PERITONEAL DIALYSIS.

Peritoneal dialysis (Photo credit: Wikipedia)

Pros

• Uses a perfectly bio-compatible membrane, the bodies peritoneum.

• Dialysis is controlled by the patient.

• Dialysis can be done in a continuous manner.

• Low blood pressure is unlikely.

• Removal of excess body fluid is more easily accomplished in a gentle manner.

Cons.

• Although the peritoneum is biocompatible it was never meant to be used for dialysis. Hence it has a set life time during which it will function as a dialysis membrane and becomes progressively more inadequate for the purposes of dialysis.

• Higher chance of treatment failure.

• Not suitable for very obese patients, patients with intrabdominal masses or hernia's

• Risk of peritoneal infection and discontinuation of dialysis.

• Not all patients may be trained to perform their own dialysis.

In terms of patient related factors, for peritoneal dialysis to be effective the patient must be highly motivated and trainable with clean suitable surroundings in which to perform exchanges. Patients have an advantage on peritoneal dialysis if they have a high peritoneal surface area to body surface area. Patients may choose peritoneal dialysis for the independence that it grants. Patients who have had previous myocardial infarction stroke or poor vascular tone are less likely to have episodes of low blood pressure on peritoneal dialysis that may result in another stroke or myocardial infarction.

Dialysis is a continuously changing process recent advances in haemodialysis and peritoneal dialysis are closing the gaps between the two. In fact recent reports suggest that nocturnal daily haemodialysis may be the closest to full replacement of renal function that we have yet seen. While development of new solutions and cyclers for peritoneal dialysis have removed some of the inherent drawbacks of peritoneal dialysis increasing benefit to patients who were previously unlikely to do well in peritoneal dialysis.

Related articles

• Peritoneal Dialysis and Encapsulating Peritonitis (allkidney.com)
• Home-based Dialysis For Kidney Failure Gaining Popularity In Developing Countries (medicalnewstoday.com)
• Peritoneal Dialysis vs Hemodialysis (drjejsrf.wordpress.com)

Warfarin may cause increased risk of stroke in hemodialysis.

Previously aspirin and clopidogrel were found to having an increase risk of mortality in patients on haemodialysis. However warfarin is known to have a survival advantage in patients with atrial fibrillation as the drug prevents clot formation in the poorly contracting left atrium of the heart. Any reduction in clot formation results in a reduction in the chance of a clot passsing from the heart into the brain resulting in an ischemic stroke. The present study looked at warfarin use in an area where it has been established to be beneficial in other patient groups. However in this study of 1671 haemodialysis patients with atrial fibrillation warfarin was found to increase the risk of stroke in a dose dependent manner. In other words the risk of a stroke was highest in patients on the highest dose of warfarin. The study incidentally did not demonstrate an increased risk of stroke due to ASA and clopidogrel this time around. However aspirin and clopidogrel are not as effective as warfarin in the normal population for the prevention of stroke and have a mixed track record in the prevention of even access related clotting. The study did note that patients who had blood tests done regularly at the centre where they are dialysed to monitor the effectiveness of warfarin and appropirately adjust the dosage of the drug had the lower risk for stroke compared to the unattended use of warfarin.

http://www.flickr.com/photos/vitualis/ / CC BY-NC-SA 2.0

This finding is to be expected as many drugs and substances interact with warfarin making it very difficult to maintain a smooth level of the drug within the body.

I suspect that warfarin use in a highly monitored setting may have some use in patients with atrial fibrillation and further studies designed to tease out this relationship will likely show that benefit.

Related articles

• Warfarin Helps Cut Stroke Risk, Researchers Report (nlm.nih.gov)

Is Aspirin safe in Kidney disease?

Generic regular strength enteric coated 325mg aspirin tablets, distributed by Target Corporation. The orange tablets are imprinted in black with "L429". (Photo credit: Wikipedia)

Low dose aspirin is a well established means of prevention of a second heart attack or stroke also known as secondary prevention. The evidence is less compelling for patients who have never had a heart attack or stroke, with the preventative benefit competing with a steadily increasing risk of bleeding from the intestines over time. Under the latter circumstances in some studies aspirin will come out ahead and in others slightly behind.

Patients on hemodialysis are at increased risk of bleeding, yet one of the main reasons for the discontinuation of dialysis remains access complications related to thrombosis (clotting). The question of whether the survival of dialysis access can be prolonged by the prescription of agents to prevent clotting has been asked before. At that time low dose coumadin therapy was associated with an unacceptably high rate of bleeding complications.

Several small studies have shown that aspirin and clopidogrel (the two main antiplatelet drugs tested) increased the risk of bleeding in patients on hemodialysis.

An article published in the clinical journal of the american society of nephrology collected data from multiple studies by a technique known as metanalysis. By combining data from multiple smaller studies the investigators hoped to gain the kind of quality statistical information required to answer the question.

The current study analysed results for 40,676 patients and concluded that the use of a single drug such as clopidogrel does not increase the risk of bleeding in patients on dialysis, the use of aspirin by itself was associated with mixed results however. In fact in patients who used grafts as a form of dialysis access aspirin increased the risk of graft thrombosis. No agent was successful at increasing primary patency of AV fistula in patients at risk of thrombosis. While using two or more antiplatelet agents increased the risk of bleeding significantly.

The current study failed to show any benefit in terms of patency rates for vascular access and overall discourages the use of antiplatelet agents in general for any form of primary prevention in dialysis patients. The role of aspirin in terms of secondary prevention of cardiovascular disease in dialysis patients is yet to be resolved.

http://www.flickr.com/photos/jypsygen/ / CC BY-NC-ND 2.0

Related articles

• Preventing Bleeding (hematuria) in Polycystic Kidney Disease (allkidney.com)
• Cannulation Technique may Improve Fistula Survival (allkidney.com)
• Questions Raised About Antiplatelet Therapy in Chronic Kidney Disease (forbes.com)

What is Shock Wave Lithotripsy Treatment.

A lithotriptor machine in an operating room. Other equipment is seen in the background, including an anesthesia machine and a mobile fluoroscopic system (or "C-arm"). (Photo credit: Wikipedia)

So you just found out you have a kidney stone and the doctor told you that you need to have a procedure called lithotripsy and you have already started to panic. Well first things first, stop breathe and read....

Lithotripsy refers to a medical procedure that uses shockwaves to break up kidney stones. The kidney stones then pass naturally in the urine or through a tube that is inserted into the kidney called a nephrostomy tube.

The sound waves used for lithotripsy pass from the outside of the body to the inside of the body , hence a better name for the procedure would be outside of the body shockwave lithotripsy. In medical jargon this translates to extracorporeal (outside the body) shockwave lithotripsy or ESWL.

On the day of the procedure you will lie on a water filled cushion. The water will conduct the sound waves to the skin and hence to the stone after being sedated, because there may be discomfort a painkiller is also administered prior to the procedure.

In some cases a tube will need to be inserted to allow the stones to pass out of the kidney. With good planning your doctor will place this before hand if necessary, however circumstances sometime dictates that this be placed after the procedure. The procedure takes generally 1 hour and you may feel unusual sensations in the area of the stone as it absorbs the sound wave energy.

Because this is a noninvasive procedure it is generally safe, however you should be aware that the stone may be too large to break up entirely in one treatment. If the stone shatters within the kidney with sufficient energy there may be bleeding. If the kidney is damaged by the stone as it breaks up it may lead to a permanent loss of kidney function in some cases. The stones may be broken up reducing them to a size where they may now move into the narrower ureters (see diagram above) and obstruct the flow of urine leading to pain which may require another procedure. The procedure is also associated with a small risk of ulceration of the stomach and small intestine.

http://www.flickr.com/photos/kidneynotes/ / CC BY-NC-ND 2.0

Your chances of having one of these complications is low, however to minimize the risk one should inform the doctor before the procedure if you are on any medication including herbs that could increase bleeding such as aspirin, and other pain killers, green tea or ginko biloba.

You should have an empty stomach for the procedure and will receive specific instructions from your physicians about when to stop eating and when you will be able to eat again.

New Drugs: Pirfenidone a new hope in diabetic kidney disease.

Diabetic nephropathy may be slowed by several means, the standard of care is blood pressure control, prescription of drugs which reduce protein in the urine and dietary changes. However the condition is almost always progressive despite these interventions.

Pirfenidone is not a particularly new drug, it has been known as an antifibrotic agent in that it reduces the formation of the primary constituent of scar tissue. Scar tissue referred to as fibrosis at the microscopic level forms as a consequence of inflammation during the process of healing.

Diabetic kidney disease has been associated with a unique type of scarring which occurs in the portion of the kidney responsible for filtering the blood. Over time this delicate filter is destroyed by fibrosis.

http://www.chemblink.com/products/53179-13-8.htm

The current study found that pirfenidone when given to laboratory mice reduced the damage to their kidneys by reducing the precursors of inflammation that lead to scarring. This is exciting news as pirfenidone directly targets a pathway that was previously not directly influenced by current therapy. This would therefore be a valuable adjunctive medication to be used alongside established treatment should the drug live up to its promise.

New Drugs: Pirfenidone a new hope in diabetic kidney disease.

Diabetic nephropathy may be slowed by several means, the standard of care is blood pressure control, prescription of drugs which reduce protein in the urine and dietary changes. However the condition is almost always progressive despite these interventions.

Pirfenidone is not a particularly new drug, it has been known as an antifibrotic agent in that it reduces the formation of the primary constituent of scar tissue. Scar tissue referred to as fibrosis at the microscopic level forms as a consequence of inflammation during the process of healing.

Diabetic kidney disease has been associated with a unique type of scarring which occurs in the portion of the kidney responsible for filtering the blood. Over time this delicate filter is destroyed by fibrosis.

http://www.chemblink.com/products/53179-13-8.htm

The current study found that pirfenidone when given to laboratory mice reduced the damage to their kidneys by reducing the precursors of inflammation that lead to scarring. This is exciting news as pirfenidone directly targets a pathway that was previously not directly influenced by current therapy. This would therefore be a valuable adjunctive medication to be used alongside established treatment should the drug live up to its promise.

Type I diabetics do not derive cardiovascular benefit fromtransplantation

A recent study has found that patients with Type I diabetes who underwent combined kidney and pancreas transplantation were found to have continued elevated levels of markers of endothelial dysfunction. The Study done in Austria comprised five different groups matched for age, gender, and body mass index. The groups comprised 10 type 1 diabetes SPK patients with non-diabetic blood glucose levels, 10 type 1 diabetes patients with poor glycemic control, 10 type 1 diabetes patients with good glycemic control, six non-diabetic patients after kidney-transplantation, and 10 non-diabetic controls. Even though glucose levels normalised in the diabetic group after transplantation certain very specific indices of endothelial dysfunction remained elevated against controls who never had diabetes.

This study should serve to increase vigilance in such patients after transplantation because they are still at risk for complications of diabetes such as stroke and heart attack despite transplantation. Despite the fact that previous studies demonstrated a significant benefit in terms of cardiovascular disease between patients with combined pancreas and kidney transplant and those that only received kidney transplantation.


Image link courtesy of http://content.answers.com/main/content/img/galeSurgery/gesu_02_img0129.jpg

Related articles

• Sun Light Helps Prevent Type 1 Diabetes (education.com)

Dialysis Info: What is the best form of dialysis access.

When a patient has been diagnosed with chronic kidney disease he or she is staged according to the national kidney foundation staging system. If they are staged as 4 to 5 then preparation is made for dialysis in the medium to short term. If the patient chooses hemodialysis as the preferred method of renal replacement therapy then the next step is an access procedure.

Q: Why is access necessary?

A: Hemodialysis requires blood to flow through a filter known as a dialyser. Toxins leave the blood in the dialyser by travelling across a semi permeable membrane and entering another fluid known as the dialysate. The dialysate and blood generally flow in opposite directions. The rate of flow of blood and dialysate is very important to the rate of removal of toxins. Blood must therefore be able to flow from the body very quickly at up to rates of 450 to 500 ml/min. The blood needs also to be returned at the same rate to prevent a fall in blood pressure. The dialysis access is the means by which blood is removed from and returned to the body.

Q: Are there different types of access?

A: Yes. There are two broad methods of gaining access to the blood stream for dialysis. One is known as a catheter which consists of a semi rigid tube with two lumen one for blood going to and the other blood going away from the patient. The other access type is known as an AV fistula which is fashioned from the veins found within your body.

Q: Is any one form of access superior to another?

A: An AV fistula is produced by a surgical procedure on the native blood vessels of your own body. This is therefore superior and more durable than a catheter. A catheter being a foreign body resides partially inside the blood stream and partly outside in order to attach to the tubing of the dialysis machine. This produces a ready site for direct infection of the blood stream and significant illness can result.

Q: How do i take care of my access.

A: The access is the lifeline of the dialysis patient without it dialysis cannot be done. Patients should make every effort to protect the access site from moisture trauma and pressure. An AV fistula is very delicate even the simple act of taking your blood pressure on the arm that has an AV fistula may be enough to destroy it. Patients should always be mindful of their access and report any changes in colour loss of pulsatility or sudden pain or swelling at the access site as an emergency.

News: Bioengineering an artificial kidney

http://www.flickr.com/photos/sriram/ / CC BY-NC 2.0

We have a problem, every year the number of patients with chronic kidney disease increases while the number of patients living on hemodialysis increases as well. This leads for an ever increasing need for dialysis which ultimately may exceed our ability to provide it. Patients enter the system on one end and should theoretically receive kidney transplantation on the other end. However transplantation programs are not able to keep pace with demand and the population on dialysis continues to grow.

What if we could create our own kidneys?

http://www.flickr.com/photos/njhdiver/ / CC BY-NC 2.0

The kidney is an organ whose anatomy has been fairly well known for some time. Modern dialysis is based on replication of some of the functions of the normal kidney. The simplest function to replicate would be the ability to filter. The filtration system of the kidney consists of what is known as glomerulus a highly specialised group of cells which somehow retain things that we need such as large proteins and simultaneously filter out small toxins that are dissolved in the blood.

The obvious observation is that this is a size selective process and the glomerulus is acting as a strainer or seive. Thus the design of modern dialysis filters is on this basis. However in the normal kidney blood flows down a set of tubes these tubes are rightly called tubules and the combination of the glomerulus and its tubule is called a nephron. A dialysis machine functions essentially as only half of this structure. There is no current commerically available machine that replicates tubular function.

If tubules were simply pipes that connected the filter to the repository of urine known as your bladder then this would be easily replicated. However each tubule is lined by cells which continually analyse the constituents of the fluid passing by it, altering it if necessary along the way by adding to it or removing things that we need to retain within our body to support life.

Recently however a paper on biomedical engineering of kidney tubules was published. This paper proposes the development of a kidney tubule on a chip. Utilizing tissue culture technique an artifical tubule would be created by transplanting either living cells from an existing kidney or tubule cells grown in culture onto a membrane and passing fluids along it in a similar manner to the normal kidney. If the cells function as they do within the normal kidney then they should be able to modify the fluid and essentially create urine.

By combining the filtration ability of existing dialysis technology with something similar to this tubule on a chip we would have a filter in series with a tubule. This is a design which is already proven to work in everyone reading this article. This would be a first step that would hopefully plug the short term need for better more physiologic renal replacement therapy.

However in the long term miniaturization of the filtration apparatus with a similar cell on chip technology may lead to truly wearable dialysis machines. Of course the smaller we make things the better and if a wearable machine can be made small enough why could it not be implanted under the skin or in the abdomen? Artificial kidneys anyone?

News: Erectile dysfunction in chronic kidney disease. What to do?.

The purpose of dialysis is to improve the patients quality of life. While there are many indices of quality of life one of the most common complaints from my patients relates to adequacy of male sexual function. The exact incidence of erectile dyfunction among patients on dialysis is unknown. However studies among the subset of patients on hemodialysis show an 82 percent incidence as published in Kidney International.

Unfortunately patients that require dialysis usually carry a high burden of disease affecting the heart, brain and circulatory systems. This results in damage to these systems that commences years before the need for dialysis. The process of hemodialysis is also known to stress these very systems that were previously damaged before the need for dialysis even arose. The unfortunate result of this is a high incidence of erectile dysfunction.

What can be done about it?

Firstly erectile dysfunction can be a complex subject that ties together desire for sexual intercourse known as libido with ability to gain and maintain an erection when appropriately stimulated. Treatment for this problem therefore starts with a detailed look at each individual case with a care provider that you are comfortable with.

In the majority of cases patients will ask me directly if they can have viagra. My response is it depends..

First of all viagra has indeed been shown to be effective in erectile dysfunction among patients on dialysis. All previously understood cautions are still advised, patients who are on a class of drugs such as nitrates have to be particularly careful as it may cause a sudden drop in blood pressure. Viagra therefore should not be taken on dialysis days as there have been reports of a fall in blood pressure on dialysis in patients that do so. Viagra also did not increase the desire for sex in any way. The loss of libido that dialysis patients frequently experience is more directly treated by ensuring adequate blood counts be maintained as well as adequate dialysis obtained.

So is viagra right for you? if you are on dialysis with no liver problems or heart problems with stable blood pressure and no need for nitrates then yes schedule an appointment and discuss it with your physician.

http://www.flickr.com/photos/51788543@N00/ / CC BY 2.0

The Wearable Kidney is here

An upcoming study in the clinical journal of the american society of nephrology is reporting the development of an artifical kidney which is wearable, you may remember that this came up a short while ago when we looked at the possible methods by which one could construct an artificial kidney. The device in question is reported to be still a dialysis machine but much smaller weighing in at only 10 pounds and literally runs on 9 volt batteries.

Even if this device is only able to give inefficient clearance per minute the health benefits over standard dialysis will be immense. Peritoneal dialysis is known for its inefficent clearance of toxin however the fact that is relatively continuous allows it to come out ahead of intermittent hemodialysis on some metrics.

Just recently a study has demonstrated that nocturnal daily hemodialysis may very well be equal to transplantation reinforcing that when it comes to dialysis the amount of time you spend actually undergoing the process is very important to survival and quality of life.

This research is very timely as another recent study has demonstrated that if you are over 60 on the transplant waiting list your chances are not very good.

With new cases of CKD continuing to rise year over year a wearable device capable of giving clearance in a more continuous daily manner as shown with nocturnal hemodialysis may be just what is needed to match the quality of life and survival benefits of transplantation.

Herbal corner: Is green tea beneficial in kidney disease?

http://www.flickr.com/photos/tim7423/ / CC BY-NC 2.0

Many herbal preparations have been marketed to patients with all manner of diseases ranging from the common cold to incurable cancer. Green tea however has been the focus of much main stream research recently with several studies of its efficacy being published. It has been shown to be effective in weight loss particularly in men, it has been shown at high concentrations to inhibit the growth of cancer cells in the lab and population studies have demonstrated some positive results where high intake of the tea reduces the incidence of gastric and esophageal cancer. There is an old saying that goes where there is smoke there is also fire. Applied to this case it would seem that there is something in green tea with very useful effects something that maybe if extracted purified and amplified may lead to a new drug. The problems with herbs however is that there are frequently impure and have many thousands of chemicals that have to be sifted through to obtain the one with the most useful medicinal effect. There is also the possibility that some useful combination of active ingredients may interact in a manner based on relative concentrations that we do not yet understand to produce the desired effect. All of this is relatively complex business and will take quite a bit of time to sort out.

What we can report currently, is that one of the most useful compounds to be derived from green tea or Camellia sinensis is EGCG. This compound is one of the most potent antioxidants ever encountered. It is likely to play a significant role in the health benefits to be derived from green tea. Administration of this compound has been shown to reduce the growth of renal cell carcinoma by a new mechanism, which incidentally is the first report of its kind for green tea.

The extracts of green tea had previously been shown to protect the kidney from drug induced damage which is common with the administration of certain antibiotics such as gentamicin.

Green tea extract has also been shown to have a potential therapeutic benefit in diabetic induced kidney disease as published here.

All of the data so far is pointing towards benefit but is there any chance of harm, how does green tea interact with medication that patients with kidney disease may be taking?

People who take warfarin, a blood thinning medication should not drink green tea. Green tea contains vitamin K and as such should be avoided for this patient group. Green has an effect on platelets, it makes them less sticky. This effect also occurs with aspirin which means combining the two may cause bleeding. In patients with chronic kidney disease which is quite severe or in patient with an acute deterioration in kidney function this may be harmful as the platelets within the body which are responsible for preventing bleeding may already be dysfunctional, green tea may cause bleeding in such patients. As with any herbal treatment or new medication speak with your health care provider before initiating treatment even if the substance is considered a food supplement such as green tea is.

New drugs: A New Option for Lupus Induced Kidney Disease

[caption id="attachment_633" align="alignright" width="250" caption="rituximab.."][/caption]

A new study published in March 2009 comparing the standard treatment of lupus nephritis i.e corticosteroids and cyclophosphamide vs rituximab was published in the clinical journal of the american society of nephrology.

Cyclophosphamide is considered a main stay of chemotherapy where it functions as an " alkylating agent" which is simply a way to express that it binds to DNA (the code that determines the function of the individual cells within the body) and destroys it.

If it were capable of destroying only cancer cells or cells of the immune system involved in lupus then it would be a perfect drug a magic bullet, unfortunately its side effects prove otherwise they include nausea, loss of hair, bone marrow suppression, predisposition to infections, sterility and ironically, with accumulating, doses even cancer. However studies have shown that up to 70% of lupus patients will respond to this drug and the side effects are not guaranteed to occur hence its continued use. Steroids on the other hand are well known to a variety of patients and come with their own problems. The price to be paid is weight gain predisposition to diabetes and recurrent infections, fluid retention, skin changes, hair growth and loss of bone mass to name a few. Steroids however are highly effective at suppressing the entire immune system by turning off the signal in between the sentinel cells that protect the body by searching for foreign invaders on a daily basis. When these cells are unable to talk to each other effectively the immune response is blunted and hence the attack of the immune system against its own body is also blunted. This leads directly to their efficacy in lupus where the immune system is overactive and a major part of the problem.

The fact is however that depending on the genetic make up of each individual patient with lupus and kidney disease these drugs may not work at all to prevent progression of the disease to the end stage. This has led to the search for alternative therapies such as rituximab.

Rituximab is a monoclonal chimeric antibody that targets b cells. Sounds almost like that magic bullet doesn't it?

This drug was designed to perform one task. Locate the cells causing the problem in autoimmune disease (the B cell) and kill it. Unfortunately B cells are also necessary for the normal functioning of the immune system so its expected that there would be increased risk of infection after taking the drug. But the hope is that there would be much less side effects associated with its therapy than the older regime.

This study had 20 test subjects nineteen women and one man side effects included five infections. A complete resolution of kidney disease was seen in 60% of the patients. The investigators concluded that rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis. The study is small however and the findings should be noted, however additional studies will be needed in the future before the drug can become a mainstay of therapy.

Unfortunately the cost of rituximab in jamaica is an issue. The drug is priced out of the reach of many people as a course costs in the region of two hundred thousand dollars.

The verdict? In my opinion try standard therapy first rituximab should only be used as a last line of defense in a patient that has tried everything already and it hasn't worked. Be aware that you are entering unknown territory to some extent.

EDIT: 14th October 2009.

The FDA has issued an advisory re: the use of Rituxan to treat Lupus. The advisory follows the death of two patients who recieved the drug for treatment of lupus. They had a rare complication of therapy known as pleomorphic multifocal leucoencephalopathy or PML.

Dialysis info channel: What is Dialysis?

Dialysis is the process by which toxins and metabolic waste products are removed from the human body as a form a therapy in patients with kidney disease. The procedure is considered organ replacement therapy in that the function of an organ (the kidney) is being replaced by a machine. However no machine is capable of adequately replacing the diverse and complex functions of the kidney. Dialysis therefore is a continuously evolving process forever attempting to achieve the unattainable perfection of full organ replacement.

There are two main forms of dialysis, haemodialysis and peritoneal dialysis. The two forms differ greatly in how they achieve the same result. While neither one is inferior to the other the older and more common modality is haemodialysis.

Haemodialysis is performed by passing blood through a circuit of tubings across a dialyser membrane which functions as a microscopic seive which preserves vitally important constituents of blood while filtering out the toxic breakdown products of daily metabolism. As blood is removed so is it continually returned to the patient so that only a small fraction of the blood is outside of the body at any one time. The procedure usually averages 4 hours and patients are free to continue a near normal life with a few restrictions in between sessions which are generally scheduled three times per week.

Peritoneal dialysis on the other hand does not involve the use artificial filtration membranes or removal of blood. Every human is born with what is known as a peritoneal membrane a one cell thick lining which covers the internal organs within the abdomen. This lining is richly supplied by blood vessels. The peritoneal dialysis procedure makes use of this by infusing fluid into the peritoneal cavity. The fluid infused is sterile, free of bacteria and toxins. Because the peritoneal lining is only a single cell thick and richly supplied by blood vessels any toxins present within the blood will slowly leech through the peritoneal membrane and into the fluid that was placed in the abdomen. After a period of time has elapsed the fluid becomes filled with toxins that have been removed from the body. The fluid can then be drained out of the abdomen and fresh fluid replaced to continue the process of dialysis. The procedure generally takes longer than haemodialysis but the patient is ambulant during that time and not confined to a dialysis chair. Patients are taught the sterile technique of self dialysis and may even perform the procedure while at work at school or on vacation at a resort. With peritoneal dialysis you take your dialysis unit with you.

http://www.flickr.com/photos/jimforest/ / CC BY-NC-ND 2.0