Very Low Protein Diet for Kidney Health

High intake of animal protein has been associated with an accelerated decline in kidney function and increased protein being spilled in the urine. However, there is a generalized fear of recommending a very low protein diet to patients with kidney disease. There is concern this diet may provoke malnutrition especially because poor nutritional status could increase risk of illness and even death in these patients. Let’s review the premise of a very low protein diet for kidney health and how it can be properly used for patients with kidney disease.

We discussed the effect high intake of animal protein has on kidney health in a previous blog. According to the National Institute of Health, the Dietary Reference Intake (DRI) of protein for the average person is 0.8-1.6 g/kg/day (or 0.36-0.75 g/lb/day). However, according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, kidney patients should limit their protein intake. A low protein diet (LPD) by the KDIGO guidelines is 0.8 g/kg/day (or 0.36 g/lb/day). That means a kidney patient who weighs 150 lbs (68 kg) has a dietary protein target of approximately 54 grams of protein per day (0.8g/kg x 68kg). Furthermore, it’s suggested that at least half of that comes from plant-based sources. Protein intake, along with other related nutrients, should be tracked closely through nutrient intake analysis, ideally by a nutritionist. 

Different dietary protein regimens have been proposed in the literature for patients with Chronic Kidney Disease (CKD): 

1. A low-protein diet (LPD), with protein target of 0.6-0.8 g/kg/day; 
2. A very low-protein diet (VLPD) (0.3 g/kg/day) supplemented with essential amino acids, or 
3. A very low-protein diet (VLPD) (0.3 g/kg/day) supplemented with nitrogen-free keto-analogues of essential amino acids.

The controversy in the literature, however, has always been whether or not lowering the targeted protein intake puts patients at risk for nutritional deficiency, including essential amino acids and other nutrients often found in high protein foods like folate, B12, carnitine, and zinc. And in that case, is supplementation among these patients necessary and useful to maintain adequate nutrition? 

Let’s focus on amino acids, but first let’s review. 

What are essential amino acids?

Amino acids (AA) are the basic organic building blocks of protein. There are a total of twenty-two AA, each composed of a core structure made of nitrogen, carbon, hydrogen and oxygen, and variable side chain groups unique to each AA. 

Of the twenty-two AA, there are nine essential amino acids (EAA). They’re called “essential” because the human body cannot make them, and therefore we must get from our diet. These EAA are: 

1. Histidine
2. Leucine
3. Isoleucine 
4. Valine 
5. Lysine
6. Threonine
7. Methionine 
8. Phenylalanine
9. Tryptophan

The remaining thirteen AA are termed “unessential” not because they’re not important, but because the body can make them through various biochemical processes as long as the necessary building blocks are available from the diet. 

When restricting protein intake in kidney patients, it is important that the patient receive adequate intake of EAA since adequate levels of these essential nutrients can only be maintained through food. This can be challenging to keep balanced, which is why we suggest working with a nutritionist to track and support adequate intake.

Using ketoacid analogues with very low protein diet for kidney health

To understand the relevance of ketoacid analogues in CKD, we need a biochemistry lesson in AA metabolism. Biochemistry isn’t everyone’s thing, so we summarized it here.

One thing to remember about AA metabolism is that it requires cofactors which are nutrients that facilitate the reactions. Vitamin B6 is a major cofactor here. Other cofactors needed in the amino acid breakdown (catabolism) include biotin, folate, and B12.

How do ketoacid-analogue supplements help in kidney disease?

Theoretically, the process described above can be used in reverse to reduce circulating nitrogen and the formation of nitrogen waste products (i.e., like urea), and, therefore, decrease the burden on the diseased kidneys.  Supplementing ketoacid analogues of EAA in kidney patients on a LPD and VLPD, might simultaneously achieve two goals: 1. It closes the gap on adequate EAA nutritional need 2. It decreases the toxic nitrogen waste products contributing to disease complications. There is also some evidence that certain analogues can decrease protein breakdown in the body.

Some studies have demonstrated that very low protein diets supplemented with ketoacid analogues decrease waste product generation in kidney disease and prevent protein-energy decline. Supplementation of keto-analogues in kidney patients was found to decrease protein in the urine as well as improve bone health, insulin sensitivity, and blood pressure control.  In addition, these dietary protein restrictions with keto-analogue supplements have been found to delay symptoms of kidney failure and the need for dialysis. 

However, one of the major concerns of supplementing ketoacids in kidney patients on VLPD is that it does not address the other micronutrients and cofactors that need to be supplemented. it also does not take into account the carbohydrate and healthy fat content of a healthy diet.

Ketoacid analogue preparations

There are a few different preparations available in Europe, but only one available in the US. If one looks at the content of these preparations, it will become obvious that the kidney patient will need several pills of ketoacid daily to achieve an adequate daily dose. This makes this therapy very expensive and impracticable.

Luckily, there’s a way to use diet to balance macronutrients to induce the same effect.  A low protein diet, with the majority of protein coming from whole food plant sources. When consuming animal protein, we recommend  organic and grass-fed sources. Strictly vegetarian patients can still get adequate sources of EAA if they plan their diet well with the help of a nutritionist. If AA supplements are determined to be needed, one should aim to achieve the recommended daily intake from a trusted source (with good quality control). According to the World Health Organization, the recommended daily dose of each of the EAA is as follows:

The bottom line on very low protein diet for kidney health

High animal protein intake is associated with faster progression of CKD, likely due to excess production of nitrogen byproducts from protein breakdown. Following a whole food plant-dominant diet can be helpful to delay the progression of kidney disease. The use of ketoacid analogues as supplements may not be practical. In order to assure that the patient is getting adequate sources of EAA and other necessary nutrients, dietary restrictions should be implemented with the help of an experienced nutritionist, preferably one trained in a personalized approach to kidney health.