Ketoanalogues and Kidney and renal Disease

Ketoanalogues and Kidney Disease

Is This The Same as a Ketogenic Diet?

The first thing I want to mention before we dive into the world of Ketoanalogues is to discuss what they are NOT. This diet, and its management, have nothing to do with the ketogenic diet or weight loss. This is a scientific dietary management approach for those with late stages of kidney disease or an eGFR of 20 or less to slow the loss of kidney function and or delay dialysis or bridge a gap for those waiting for a kidney transplant.

Now that we have that covered let’s dive into what is involved with a Ketoanalouge diet and how to implement it.

What Are Ketoanalouges?

The manipulation of dietary protein intake is the mainstay of nutritional treatment of patients affected by end-stage chronic kidney disease. Dietary interventions aim to reduce the burden of uremic toxins in order to decrease uremic toxicity and delay the need for dialysis as well as reduce the acid load on the kidneys by employing a more alkaline diet. There is scientific consensus that exists regarding the benefit of protein restriction in delaying the progression of renal failure and the need for dialysis.

In addition, supplements play an important role as a means to obtain both beneficial effects and nutritional safety when implementing a low protein diet.  Essential amino acids and Ketoanaloguesmixtures are the most utilized types of supplementation in CKD patients on restricted protein regimens. The essential amino acids plus Ketoanalogues supplementation is mandatory in conjunction with a very low-protein diet in order to assure an adequate essential amino acid supply to support the thousands of essential biochemical processes in the human body that a normal level of protein intake provides. 

The addition of ketoacids or Ketoanalogues prevents patients from experiencing severe malnutrition while following a protein-restricted diet. 

Keoalanlgues and renal disease and kidney disease

So What Exactly is a Ketoacid or Ketoanalouges

In a nutshell, Keto-acids / Ketoanalogues lack the amino group bound to the alpha carbon of an amino acid so they can be converted to their respective essential amino acids without providing additional nitrogen that adds additional strain to the kidneys. They, however, still manage to provide all the requirements of normal amino acids which are the building blocks of protein.

Ketoanalogues were first used back in 1973 in addition to a low protein diet by Dr Mackenzie Walser. Dr Walser was a nephrologist who died in late 2006. He was a critical and unorthodox thinker who tackled difficult clinical and physiological problems with answers that invariably added new insights to the field of nephrology.

Walser graduated from Columbia University’s College of Physicians and Surgeons and completed his medical residency at Massachusetts General Hospital. He then began postdoctoral training with Donald Seldin at the University of Texas Southwestern, where he later joined the faculty. 

Walser was highly interested in the use of dietary methods for treating patients with CKD or other diseases such as liver disease or errors of the urea cycle that are characterized by protein intolerance. Scientifically, he provided numerous insights into the difficult metabolic problems encountered by these patients. He also championed treatments for problems of CKD patients in three books, which outline how patients can avoid complications of kidney disease.

However, his diet that was originally used was very high in inflammatory provoking foods, such as white bread, pasta, and lollies. Today we aim to increase healthy fats instead to get the caloric intake up rather than lots of refined carbohydrates that can contribute to both diabetes and heart disease.

Why Are Protein and Nitrogen an Issue in Chronic Kidney Disease?

​​Amino acids are the building blocks of protein. However, nitrogen is normally a part of these amino acid chains. Nitrogen is thought to be the main instigator of creating a higher uremic load on the kidneys. Removing the nitrogen from the amino acids which is what a keto analogue is, reduces the uremic load placed on the kidneys. The beneficial effects of protein restriction supplemented with Ketoanalogues on the progression of CKD are multifactorial and may include decreasing nitrogen waste, oxidative stress and inflammatory responses including transforming growth factor-beta and protection against hemodynamic changes in glomerular hyperfiltration. 

https://www.krcp-ksn.org/journal/view.php?doi=10.23876/j.krcp.18.0055

Dietary protein plays an important role in the progression of CKD, and a low protein diet is recommended for patients with advanced CKD to slow the decline in the glomerular filtration rate. Additionally, several clinical trials and meta-analyses have documented that very low protein diets supplemented with Ketoanalogues preserve the rate of progression of advanced CKD 

https://pubmed.ncbi.nlm.nih.gov/1591358/

and delay the need for long-term dialysis treatment among patients with advanced CKD. 

https://pubmed.ncbi.nlm.nih.gov/17472838/

Nitrogen breaks down into something called TMAO, also known as Trimethylamine-N-oxide (Read more about TMAO here) and uremic acids. 

TMAO (or Trimethylamine-N-oxide) is a metabolite produced by gut bacteria from choline, phosphatidylcholine and L-carnitine-rich foods (mainly fish, meat, eggs and dairy). When consumed, these nutrients are processed by gut bacteria resulting in the release of various metabolites including TMA (Trimethylamine) into the blood. TMA is then transported to the liver where it becomes oxidised into TMAO, primarily by the enzyme FMO3. TMAO is then excreted in the urine. 

Elevated levels of TMAO in the body have been linked to a wide variety of diseases including:

  • Cardiovascular disease- including blood clots, heart attack, stroke, heart failure
  • Atherosclerosis (hardening of arteries)
  • Diabetes
  • Bowel cancer
  • Chronic Kidney Disease
  • Inflammation
  • Liver Dysfunction- liver damage and non-alcoholic fatty liver disease
  • Obesity 
  • Neurodegenerative disease

TMAO promotes the release of inflammatory factors throughout the body, this inflammation can directly cause damage to the kidney. TMAO also contributes to renal fibrosis. Renal fibrosis or scarring is a process that drives the progression of CKD to end-stage kidney disease.

Studies have shown that TMAO is linked to kidney disease via the following mechanisms.

  • Elevated levels of TMAO are associated with progressive loss of kidney function and the development of CKD
  • People with CKD commonly have higher levels of TMAO
  • Elevated TMAO levels in people with CKD are associated with higher rates of adverse cardiovascular disease events and mortality
  • Inhibiting TMAO production can prevent both renal functional impairment and fibrosis (scarring)
  • Animal studies have shown that elevated TMAO levels significantly increased renal inflammation and renal fibrosis (scarring)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203662/pdf/nihms-1576640.pdf

https://pubmed.ncbi.nlm.nih.gov/29061990/

What is a Low Protein Diet?

A low protein diet aims to restrict protein intake to between 20 – 40 gms of protein per day depending upon the size, age and gender of the client. Generally, younger males who are still fairly active require a slightly higher protein intake to preserve muscle mass.

Low Protein Diets for Kidney and renal disease

20 gms of protein is the equivalent of a chicken breast, which would be the TOTAL amount of protein allowed to be consumed in a day.

Calories are bumped up by using high-quality good fats coupled with plenty of alkaline vegetables. The addition of highly alkaline foods coupled with a low protein diet further helps support healthy kidney function and reduces an unnecessary toxic load upon the kidneys by reducing the uremic load and TMAO production.

The diet is followed for 3 – 4 months and then the eGFR is rechecked to make sure that the eGFR is stable or even improved. 

What would a typical day’s food intake look like on a low-protein diet?

We highly recommend working with a renal dietician who specialises in Ketoanalogues to make sure that you are meeting all of your nutritional needs. The diet needs to be plant-based and contain good quality fats rather than highly refined carbohydrates like bread, biscuits and lollies.

A typical days diet might look like this:

Breakfast

Blueberry smoothie with nut butter

Snack

Blueberries or an apple

Lunch

Hummus and steamed vegetables with olive oil and olives

Dinner

Vegetable stir fry with jasmine rice

Curry with rice

Addition of avocado, olive oil, olives and nuts and seeds to bump up good quality fat intake.

Low protein diets and Kidney disease

These diets are also supplemented with a good quality multivitamin and we would also add Kidney Primer® and Kidney Advance® to really get the best results in improving renal function and of course, Ketoanalogue supplementation to ensure protein needs are being met.

What sort of results will I see following a Ketoanalogue diet?

Study outcomes are very promising using this method. Patients tend to report anything from having more energy, less brain fog, weight loss, a stabilising in kidney function or even an improvement in eGFR numbers. For others, it is all about buying time to be able to have a kidney transplant.

There are lots of clinical trials reporting the benefits of using this approach in the late stages of kidney disease. Some of these studies can be found below:

This first study showed that over a 9-month period following the diet eGFR numbers were preserved as well as maintaining their BMI

https://pubmed.ncbi.nlm.nih.gov/15060873/

This study showed that a very low protein diet was very safe and helped to preserve kidney function over a 23-month period.

https://pubmed.ncbi.nlm.nih.gov/17472838/

This study also showed that a very low protein diet coupled with supplementation of Ketoanaloguesdelayed kidney decline in those waiting for dialysis or transplantation.

https://www.krcp-ksn.org/journal/view.php?doi=10.23876/j.krcp.18.0055

In 2017, there was a great review paper written by Dr Gang Lee Ko on protein intake and chronic kidney disease.

His review concisely identified eight different potential benefits of a low protein diet:

  1. Ability to slow the decline of GFR
  2. Decreased proteinuria (that’s when you have protein spilling into your urine)
  3. Decreased uremic toxins
  4. Decreased oxidative stress (that’s inflammation)
  5. Decreased metabolic acidosis
  6. Decreased phosphorus and parathyroid hormone (has to do with bone health among other things)
  7. Decreased insulin resistance
  8. Decreased blood pressure

https://pubmed.ncbi.nlm.nih.gov/29094800/

Are there any side effects or reasons that I should not follow this diet?

Firstly we only recommend following this diet is you are in the end stages of kidney disease or have an eGFR of 20 or less. We also highly recommend following this diet under the supervision of a renal dietician trained in Ketoanalogues and low protein diets as it is very easy to end up malnourished if it is not done properly. 

Possible negative effects of the diet include:

  • Malnourishment
  • Protein deficiency

Symptoms of protein deficiency can include:

  • nausea.
  • headache.
  • mood changes.
  • weakness.
  • fatigue.
  • low blood pressure.
  • hunger and food cravings.
  • diarrhea.

It is important to remember that protein is not the enemy here, it is simply being reduced to take the load off the kidneys. We often see clients and patients become scared to eat anything with protein in it which leads to either malnourishment or an inability to stick with the diet. 

What dosage of Ketoanalogues do I take?

There are two main ways in which Ketoanalogues can be taken, tablets or powder.

Tablets 

Albutrix and Ketosteril® seem to be the two most popular brands on the market.

The dosage for Albutrix is unless otherwise prescribed by your nephrologist, renal dietician or GP if not otherwise prescribed, take 4-8 tablets three times a day during meals. Swallow whole. This dosage applies to adults with a weighted average of (70kg/BW).

The dosage for Ketosteril according to the package, starts at 2 tablets three times a day. Product details include 1 pill containing 4-5 grams of protein. Six pills include 30 grams of dietary protein.

Powders

Ketorena is a popular powdered version of the Ketoanalogues.

Ketoanalouges and renal disease

A single scoop of Ketorena contains 2100 mg or 2.1g of keto/amino acids. Most, but not all tableted keto-analogues contain 600mg of keto/amino acids per tablet.

Ketorena can be taken 2-3 times per day depending on the converted dose.

A typical dose conversion may look like this: 600mg tablets x 10 per day = 6000mg or 6g total daily dose

1 scoop of Ketorena: 2100 mg or 2.1g x 3 = 6300mg or 6.3g total daily dose or 1 scoop 3 times per day.

Final words

Our approach here at Kidney Coach is that prevention is always better than cure. That being said for people who are already in stages 4-5 of kidney disease or for those wanting to prolong the need for dialysis or bridge the gap between dialysis and a transplant then low protein diets in conjunction with Ketoanalougues could be potentially helpful in stabilising kidney function and buying time. 

I don’t feel that this is a long-term strategy but as a short-term intervention to stabilise function while the underlying cause(s) of kidney disease are investigated and treated then this might well be a very sensible approach.

Most Ketoanalogues are calcium based so before starting this diet it is imperative that you talk to your specialised and make sure that your calcium levels are monitored especially for those with heart disease or issues with their parathyroids or clearing calcium.

I also recommend that anyone looking at this approach work with a qualified renal dietician to set you up for success. If you have enjoyed this article head over to our Facebook page and leave us a comment or feel free to share this article with family and friends. You never know whose life you may change. 

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