Ketoanalogues: How This Medical Food Can Keep Kidney Function

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Ketoanalogues are an increasingly fascinating part of the renal diet. The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) published nutrition updates in 2020 to include evidenced-based practices of the renal diet.

But what are ketoanalogues? Are they for anyone with kidney disease? How do you know when to take them? How do you know which are actually ketoanalogues? Learn all that and more in this article.

Please speak with your physician prior to starting any new supplements. It is best practice to work with a renal dietitian when following the protocol below.

The Low and Very-Low Protein Diet

Before we dive into more about ketoanalogues, it’s important to first understand the low protein diet. Ketoanalogues are used with a low protein or very low protein diet.

The low protein diet is anywhere from 0.55-0.8 grams of protein per kilogram of body weight. According to the KDOQI guidelines, a low protein diet is for stages 3-5 CKD.

The very-low protein diet is a diet with 0.28-0.43 grams of protein per kilogram of body weight along with ketoanalogues to meet protein requirements. With the ketoanalogues, protein intake should reach 0.55-0.6 grams protein per kilogram body weight. 

Basically, the ketoanalogues help to prevent protein wasting and deficiencies.

Learn more about the low protein diet here.

Who should be on a low protein diet?

According to KDOQI, those in stages 3-5 without diabetes and metabolically stable may benefit in kidney protection with a low protein diet.

Those in stages 3-5 and also have diabetes will have a modified low protein diet of approximately 0.6-0.8 g/kg/day.

Be sure to speak with your physician to get a referral to a dietitian. If you can’t get a referral, you can check out the Kidney Foundation’s Dietitian Directory or my page here which includes other countries’ dietetic associations.

What does metabolically stable mean?

Metabolically stable means there is no active inflammatory or infectious disease present, no recent hospitalization, and no diseases like cancer. 

If you have diabetes, this means blood sugars need to be well-controlled.

What are ketoanalogues?

Ketoanalogues are breakdown forms of amino acids, aka protein building blocks. However, they include a part of the amino acids but without the nitrogen component.

Nitrogen is harmful to kidney health as it can build up. This can be seen in the renal function panel as part of one’s Blood Urea Nitrogen.

Amino Acids

As mentioned above, amino acids are the building blocks of protein. They play many roles in the body, beyond protein and muscles.

Amino acids also help with synthesizing hormones, neurotransmitters, enzymes, transporters, tissue and cells.

Essential Amino Acids

There are nine essential amino acids. The reason they are deemed “essential” is because they cannot be made in the body.

The nine essential amino acids are:

  • Histidine
  • Isoleucine
  • Leucine
  • Lysine
  • Methionine
  • Phenylalanine
  • Threonine
  • Tryptophan
  • Valine

Non-essential Amino Acids

Non-essential amino acids are just that, non-essential. Therefore, our body is able to make these based on other amino acids and components in the body.

There are eleven non-essential amino acids. They are:

  • Alanine
  • Arginine
  • Asparagine
  • Aspartate
  • Cysteine
  • Glutamate
  • Glutamine
  • Glycine
  • Proline
  • Serine
  • Tyrosine

These amino acids are synthesized from glucose, with the exception of tyrosine. Tyrosine is made from phenylalanine.

How are ketoanalogues different from amino acids?

As mentioned above, ketoanalogues are a portion of amino acids. 

The amino acid supplements typically found over the counter in supplement and health food stores will be the complete amino acid, still with the components that are harder for the body to break down.

When should you take ketoanalogues?

Now that you know about ketoanalogues, it’s important to determine exactly who may benefit from them. Just because you have kidney disease does not mean you should be taking ketoanalogues.

Stage 3 CKD

According to KDOQI, those at CKD3 that are metabolically stable may benefit from a low protein diet, “with or without ketoanalogues.”

However, ketoanalogues are not seen as a first line of defense at stage 3 kidney disease. The interventions recommended prior to this supplementation may include:

  • Low protein diet
  • Low sodium diet
  • Blood sugar control and management

That being said, ketoanalogues may have a place in supporting those with stage 3 kidney disease if a significant drop in kidney function has been identified.

Stages 4 and 5 CKD

Stage 4 CKD is for GFR between 15-29. Stage 5 kidney disease is when the GFR is under 15. This is also the stage at which a person can qualify for dialysis and transplant.

Many, however, cannot or choose not to start dialysis and make dietary changes instead. At this point, a low protein or very low protein diet can be an essential part of the dietary interventions.

Dialysis with Residual Renal Function

In some cases, those that start dialysis and have a small percentage of kidney function remaining may be advised to use ketoanalogues.

It’s extremely important to discuss ketoanalogues with your dialysis team first as KAs are reliant on the residual function of your kidneys. Ketoanalogues are not proven to lead to stopping dialysis treatment. 

Never stop dialysis treatment before first discussing with your nephrologist and healthcare team as dialysis is a life-saving treatment.

When Should You Not Take Ketoanalogues?

If you have healthy functioning kidneys, there is no need to take ketoanalogues. They are to support those with lowered kidney function.

If you have high calcium or magnesium levels in your blood test results prior to starting ketoanalogues, you need to first consult with your physician and dietitian.

Potential benefits of Ketoanalogues

Ketoanalogues have been studied for many years to determine the benefits of including this supplement for those with kidney disease. Some of the potential benefits are:

  • Slow GFR decline
  • Decrease serum creatinine and BUN levels
  • Lower oxidative stress
  • Decrease metabolic acidosis
  • Better phosphorus and parathyroid hormone level management
  • Decrease insulin resistance
  • Improved blood pressure
  • Reduced proteinuria
  • Delayed start of dialysis

An observational study in 2018 found that a group following the low protein diet with ketoanalogue supplementation had a lower risk of all-cause mortality, cardiovascular and cerebrovascular events, and infection-related death.

A study published in 2021 found that ketoanalogue supplements reduced mortality in predialysis patients with diabetic kidney disease. However, ketoanalogues are recommended for those with well-controlled diabetes.

It’s important to know that most of these results are based off of studies of those with stages 4 and 5 kidney disease.

Where Ketoanalogues Have Not Been Proven to Help

While KAs have shown some great benefits, as mentioned above, there are areas that did not show benefits.

Some areas that did not show improvement with ketoanalogues include:

  • Cholesterol levels
  • Albumin levels
  • Anemia & hemoglobin
  • Lean body mass and BMI

For these reasons, it’s important to understand that ketoanalogues can help many things, but it’s not a magic “cure-all” for kidney disease.

Types of Ketoanalogues Available

Ketorena

Ketorena is a calcium-based ketoanalogue sold in both powder and tablet form. It’s a combination of the essential amino acids.

Ketorena was developed by a board-certified nephrologist in the United States. It includes the following ketoanalogues:

  • L-lysine acetate
  • Alpha-ketoleucine calcium
  • Alpha-ketovaline calcium
  • Alpha-ketoisoleucine calcium
  • L-Threonine
  • L-Histidine
  • L-Tyrosine
  • L-Tryptophan

Other ingredients include maltodextrin, L-Ornithine HLC, Silica and Sucralose.

Dosing

According to the Ketorena website, the typical dose is 1 scoop three times daily with food. Mix the powder into 3-4 ounces of water.

For the tablets, typical dose is 3 tablets three times a day with meals.

Cost

At the time of this article’s publication, Ketorena costs $145.50 per 90-serving canister (a one-month supply based on typical dosing).

However, purchase at least 2 canisters to get a 30% discount. This will result in a price-per-canister of $99.75 per month.

Unique Features of Ketorena

Ketorena has a low calcium content and no magnesium, which can be helpful as people with chronic kidney disease can be at risk for both elevated calcium and magnesium levels.

It is offered as either a vanilla-flavored powder or tablet. According to the website, one scoop of the powder is equivalent to 3-4 tablets of KAs.

Where to order Ketorena

Go directly to the Ketorena website to order straight from the manufacturer. It’s not advised to purchase through Amazon or other third-party sellers as the quality may be in question.

Albutrix

Albutrix is a magnesium-based ketoanalogue product that comes in tablet form. There are three different products available. Each KA is for the different stages of CKD that may benefit from ketoanalogues with a low or very-low protein diet.

Lee Hull, a patient with FSGS, developed Albutrix. The name may sound familiar as he has written a popular book, Stopping Kidney Disease.

According to the website, the Albutrix-S5 (stated for stage 5 CKD) includes the following ketoanalogues:

  • Leucine
  • Isoleucine
  • Valine
  • Methionine
  • Phenyalanine

Other ingredients include L-lysine monoacetate, L-Threonine, L-Histidine, L-Tyrosine, L-Tryptophan, maltodextrin, Kollidon CL, microcrystalline cellulose, colloidal silicon dioxide, salc, starch, magnesium stearate, hypromellose, and polyethylene glycol.

Albutrix-S4 and Albutrix-S5 also include nutrition information for calcium, magnesium, and nitrogen. The nutrition information differs since there are different ketoanalogues for different stages of CKD.

Dosing

According to the package, dosing generally starts at 2 tablets three times a day.

Product details include 1 pill as containing 4-5 grams protein. Six pills include 30 grams of dietary protein.

Cost

At the time of this article publication, one bottle with 180 tablets (approximately a one-month supply based on general dosing) is $199.

A discount is offered if a monthly subscription service is started, at which point the price per month is $179.10.

Unique Features of Albutrix

Albutrix sells three different types of ketoanalogues: Albutrix-S3, Albutrix-S4 and Albutrix-S5 that are all supposed to coordinate with different stages of kidney disease.

It is recommended to choose the different ketoanalogue based on magnesium levels of your most recent blood test. The Albutrix-S3 contains 360 milligrams magnesium for six tablets. Albutrix-S4 contains 180 milligrams of magnesium for six tablets. 

Finally, Albutrix-S5 contains no magnesium but instead calcium. There are 459 milligrams of calcium per daily serving.

Where to order Albutrix

Go directly to the Albutrix website to order straight from the manufacturer. As mentioned, an automated monthly subscription will give a discount of about 10%.

Ketosteril

Ketosteril is another calcium-based ketoanalogue. It was created from Fresenius, a well-known dialysis company. It includes the following ingredients:

  • Calcium-3-methyl-2-oxovaleric acid
  • Calcium-methy-2-oxovaleric acid
  • Calcium-2-oxo-3-phenylpropionic acid
  • Calcium-3-methyl-2-oxobutyric acid
  • calcium-DL-2-hydroxy-4-(methylthio)-butyric acid
  • L-lysine acetate
  • L-threonine
  • L-tryptophan
  • L-histidine
  • L-tyrosine

Other ingredients include corn starch, crospovidone, povideone, talc, highly dispersed silicon dioxide, magnesium stearate, macrocol 6000, colouring agents E104, E171 alkaline polymethacrylate, glycerol triacetate.

The total nitrogen content per tablet is about 36 milligrams. Total calcium content is 0.05 grams.

Dosing

Ketosteril directions are for 4-8 tablets three times a day during meal. 

Cost

At the time of this article publication, cost varied slightly between some of the online drug stores that sold Ketosteril. However, the general cost of one box with 100 tablets was approximately $90.

For a full month’s supply with the starting dose, it would come out to $360 per month.

Unique Features of Ketosteril

This ketoanalogue is available by prescription only.

Where to Order Ketosteril

There are several online pharmacies that offer Ketosteril. However, it would be best to first speak with your nephrologist to see if they would be able to order it. 

There are potential risks for scams when ordering in unfamiliar sites that are not the direct manufacturer, including ordering on Amazon.

Labs to Track

Since ketoanalogues are a part of preventing kidney disease progression, it’s important to continue to monitor labs. This is another reason why it is important to first discuss with your physician.

Some of the labs that you should discuss monitoring with your physician include:

  • Complete blood count (CBC)
  • Renal function panel
  • Magnesium
  • Prealbumin
  • Urine analysis

According to Ketorena, these labs should be checked every 2-4 months. So, other labs to be evaluated every 4-6 months or yearly include:

  • Albumin-to-creatinine ratio
  • Protein-to-creatinine ratio
  • Iron
  • Intact PTH
  • Vitamin D
  • Hemoglobin A1c for those with diabetes
  • Lipid panel for those with high triglycerides, cholesterol, or other lipid abnormalities

Other Questions about Ketoanalogues

Does health insurance cover ketoanalogues?

Unfortunately, health insurance does not cover the cost of ketoanalogues. Because of this reason, cost is often the biggest barrier when it comes to using KAs.

You may be able to use a health savings account to purchase ketoanalogues as they are a medical food. Check with your HSA provider before purchasing. 

Another option is to keep receipts for a tax deductible medical expense.

How are ketoanalogues different from branched-chain amino acids?

Branched-chain amino acids (or BCAAs) are three of the essential amino acids: leucine, isoleucine, and valine. Their chemical structure is what makes them branched-chain amino acids.

Ketoanalogues include the branched chain amino acids. However, BCAAs do not include the other essential amino acids that ketoanalogues do.

A study in the Journal of Renal Nutrition in 2020 looked at the use of BCAA-enriched dialysis fluid to see if it would support amino acid levels. 

They did find that the supplemented fluid used in the dialysis treatment helped with plasma concentrations. Of course, more research is needed to verify long-term benefits and outcomes.

What about liquid aminos?

Liquid aminos are basically amino acids that are from soybeans. As an amino acid and not a ketoanalogue, they will still have the nitrogen piece.

Therefore, liquid aminos like Coconut Secret or Bragg’s are not equivalent to ketoanalogues.

An important consideration when using liquid aminos is the sodium content. This can range from 90mg to several hundred milligrams of sodium per serving. Be sure to read the label so you know how much sodium is in your liquid aminos.

Are ketoanalogues related to the keto diet?

It may sound confusing, but ketoanalogues have nothing to do with the high-fat, low-carb diet known as the keto diet.

If you’d like to learn more about the keto diet and kidney disease, click here.

Are there side effects with ketoanalogues?

Potential side effects of ketoanalogues can be high levels of calcium or magnesium. This is why it’s important to speak first with your doctor about ketoanalogues so you can develop the right tracking process.

There are no common side effects otherwise noted.

How long does someone need to take them for?

The length of time ketoanalogues are needed in the diet will depend on many factors. Changes in kidney function, lab test results, and other health conditions may change the dosing or even result in completely stopping KA supplements.

The recommended minimum length of time to use ketoanalogues is generally three months, unless otherwise indicated by your physician or dietitian.

The Bottom Line 

Ketoanalogues can be an important part of a renal diet that is aimed at stopping progression of chronic kidney disease.

However, there is risk of aggravation and further kidney disease progression if taken without proper medical supervision.

It’s important to discuss any and all supplements prior to starting with your healthcare provider to ensure it’s the right thing for you. 

And with ketoanalogues, it is especially important to work with a renal dietitian to ensure that you’re getting the right amount of protein from both ketoanalogues and your diet.

Learn more

Prior to starting ketoanalogues, it’s important to understand the low protein diet. Click here to read more about the low protein diet.

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