There has been a persistent myth in the nutrition and supplementation landscape for decades that a diet high in protein, or too much supplemental protein can damage the kidneys and even lead to kidney failure.
This particular myth dates back decades, and there is a relationship between dietary protein and kidney function.
I think that this reoccurring link that keeps getting made between high protein diets and kidney damage stems from a few different areas, which I’ll break down below!
The kidneys play various roles in the body, primarily in regulating blood and the waste products in it. The kidneys also balance water and electrolytes, activate vitamin D, and produce certain hormones.
Waste products do come from metabolising protein, and the kidneys do play a role in the clearance of this waste.
However, just because kidney function AKA the kidneys workload increases, does not mean it is inherently damaging.
A loose analogy might be saying that muscle function increases when exercising. This is not necessarily dangerous for the muscles… they are designed for these periods of increased work.
The body metabolizes food to produce energy or to break down the macromolecules in food. Food is broken down into the building blocks you need for creating and maintaining your organs, tissues, and other structures in the body.
In the process of metabolising food, some substances are produced which must be eliminated so as not to accumulate in the body to a toxic level. The kidneys play a major role in the elimination of waste products.
Kidney function in response to protein feedings has been studied since the early 1900s.
In 1923 Addis and Drury observed a relationship between the level of dietary protein and the excretion rate of the waste product urea.
Protein and its effects on urea excretion, kidney damage, and chronic kidney disease risk have been studied ever since.
What’s Special About Protein?
Protein macromolecules are made of individual units or ‘building blocks’ called amino acids.
Unlike carbohydrates and fats, all amino acids contain a nitrogen atom in their amino group. When the body breaks down amino acids, the nitrogen is split off and forms ammonia, which is a highly toxic compound to the body.
To get rid of ammonia the liver converts it to urea, which is a water-soluble, non-toxic waste product that the kidneys then need to excrete in the urine.
To review: proteins are broken down into amino acids.
When metabolised, nitrogen-containing amino acids undergo ‘deamination’, which removes their nitrogen component -but produces ammonia.
Ammonia is cytotoxic (toxic to cells) and must be removed from the body but there is no real pathway for the body to excrete ammonia.
The liver is the body’s primary detoxification organ, and it removes ammonia from circulation, turns it into urea, and exports the urea out into the bloodstream for excretion.
The kidneys filter the blood. Here, urea is separated out of the blood. The red blood cells and various other components of blood are kept, and waste products (i.e. urea) are expelled in urine.
Evidence of Protein Damaging the Kidneys…
A journal article in The New England Journal of Medicine, “Dietary protein intake and the progressive nature of kidney disease” was published in 1982 and is still often cited when linking dietary intake and the progression of chronic kidney disease (CKD).
To understand why some of the links between increased protein intake and kidney damage have been made, it is helpful to have a basic understanding of the nature of kidney disease and the progression towards renal failure.
Chronic Kidney Disease: A Progression
Chronic kidney disease (CKD) is a progressive disease that begins as a gradual decrease in kidney function that is persistent for greater than 3 months. Over time, decreases in function become more pronounced, as do the potential long term consequences and effects on the body.
CKD is split into various stages. Staging is done based on the rate glomerular filtration rate or “GFR”, which is a measure of how well the kidneys are filtering blood.
eGFR is measured by estimating how many millilitres of fluid is filtered by the kidneys, per minute, per 1.73 square meters of body surface area.
In a normal healthy person, GFR is usually greater than 90. On average it is lower in women compared to men and it does gradually decrease as we age.
One of the major clinical factors leading to the diagnosis of CKD is a GFR of less than 90 that persists for periods longer than 3 months.
The stages are summarised in the image below, but stage 1 typically signifies some damage to the kidney, but actual kidney function is still normal or even increased.
Stage 2 is classified as a mild loss of kidney function and a notable decrease in GFR. GFR continues to decrease at each stage, with each stage presenting various nutritional considerations. Stage 4 is the final stage before kidney failure.
Once reaching stage 5, ongoing dialysis or a kidney transplant is required for survival.
The progressive loss of kidney function is due to the failure of nephrons, which are the functional units of the kidneys as detailed in the image below.
As some nephrons fail, the additional load is distributed among the remaining nephrons, which work harder to pick up the slack. Eventually, the remaining nephrons become exhausted and also fail. This can sometimes explain the increase in kidney function seen in the early stages of CKD prior to the inevitable decline.
In stage 5, the loss of nephrons becomes too great to filter and remove waste from the blood, uremia (high urea in the blood) occurs.
Uremia is a syndrome of malaise, weakness, nausea, vomiting, muscle cramps, itching, metallic taste in the mouth, and neurologic impairment that is brought about by an unacceptable level of nitrogenous wastes (i.e. urea) in the body.
Uremia can lead to encephalopathy, heart failure, stroke, coma, and death if untreated.
So How Does Protein Affect the Kidneys?
The 1982 journal article from Brenner et al (mentioned earlier) “Dietary protein intake and the progressive nature of kidney disease” proposed potentially harmful effects to the kidneys through consumption of the modern high-protein diet.
It was shown that higher protein intake leads to glomerular ‘hyperfiltration’. This is the increase required in kidney function to filter out a higher load of waste. The rate of glomerular filtration and pressure in the glomerulus itself both increased in response to protein feedings.
Much of the evidence cited in this article was generated from animal studies or from patients who also had existing renal disease. It is therefore problematic to extend this relationship to healthy individuals with normal renal function.
These increases were then proposed to lead to renal injury (i.e. damage to the nephron), and increase the risk for the development of CKD, or, if already existing, increase the progression of the disease.
Human kidneys have what is called a ‘functional reserve volume. Basically, this means that not all of the functional units of the kidneys are being used all of the time.
There is a graduated increase in work done by the kidneys as needed depending on the solute (or waste) load in the blood.
To use another loose analogy with the muscles – when picking up something light you don’t use ALL of the possible strength you have to pick the thing up. You just use as much as is needed to do the job. The remaining unused muscle is sitting there to be used if needed – i.e. ‘in reserve’.
Human kidneys can upregulate their activity when higher levels of filtration are needed. The increased load is distributed across the whole kidney rather than individual nephrons as a protective mechanism to help avoid damaging individual nephrons. This is a normal adaptive response allowing the kidney to respond to fluctuations in the amount of waste management required.
While the use of a protective functional reserve is possible with healthy kidneys, it might not be the case with compromised kidneys. As you can see in the image above, the functional reserve decreases as the number of nephrons decreases.
Only in those with a limited functional reserve, at certain stages of diagnosed chronic kidney disease, or with existing kidney issues, may it be necessary or beneficial to reduce protein intake.
However, even this depends on individual circumstances. For example:
“While protein restriction may be appropriate for treatment of existing kidney disease, we find no significant evidence for a detrimental effect of high protein intakes on kidney function in healthy persons after centuries of a high protein Western diet.”
Further to that point, even in chronic kidney disease, it is not one size fits all “eat low protein” approach. For example, going too low in protein is likely to increase the risk of protein-energy malnutrition and muscle wasting.
So even in what is widely considered to be standard practice for consuming low protein there is still some debate in the literature, summarised briefly in the images below.
Other Things That Might Be Causing Confusion:
The most common marker of decreasing kidney function is GFR. The GFR that you get back after a blood test is not a direct measure of the glomerular filtration rate/kidney function.
This measure is actually “eGFR” or estimated glomerular filtration rate. eGFR is a proxy for actual kidney function and the ‘estimation’ part comes from the formula used to calculate GFR, which looks like this:
You can see that serum creatinine (i.e. the amount of creatinine in the blood) is the main variable in the equation. Therefore things that increase creatinine in the blood may falsely reflect a decreasing GFR.
What Is Creatinine?
Creatinine is a waste product that is formed by skeletal muscles when they use creatine. Creatine is found in foods such as red meat and seafood – foods that are typically consumed on a higher protein diet.
Another compound that significantly increases creatinine levels is the supplement creatine which is typically used to boost muscular strength and power. Creatine is one of the most common, safest, and most widely researched performance supplements in the world.
There’s a good chance that many of the people on a high protein diet are interested in their health and fitness. They are likely on a higher protein diet to support recovery and muscle gain from the strength training they are doing. Many of these people may also be using the very popular bodybuilding supplement creatine…
You can perhaps see where I’m going with this: Kidney function is estimated from GFR, which is estimated from creatinine in the blood. Protein and creatine increase creatinine (but don’t actually damage the kidneys).
Elevated creatinine from these supplements can give a false flag for decreasing kidney function.
These interactions between protein, creatine, creatinine, eGFR and kidney function can most definitely be confusing. This confusion isn’t limited to the general public and many practitioners may not have a thorough understanding of such a niche area. In my opinion, this is also a likely factor in the persistent myths that high protein diets (and creatine) can damage the kidneys.
An Example of This in Practice…
This case study is a good example of such a misdiagnosis of kidney injury via measuring eGFR and creatinine levels in someone training 5 days per week, eating a high protein diet, and using creatine.
Initial blood tests showed an eGFR of 33mL/min and 28mL/min (healthy range is considered over 90). Other tests of kidney function, such as the serum albumin showed no problems with the kidneys.
The doctors had the patient stop creatine and protein supplementation due to fears of kidney failure, and referred on to a specialist. A few weeks later the patient was retested, creatinine levels had dropped, and eGFR was measured as normal.
All other markers of health were also normal, and it was concluded that the supplements were the cause of the false readings and no damage to the kidneys was present.
“Clinicians can often assume by default that an elevated serum creatinine indicates that the kidneys are not clearing creatinine effectively. It is rarely considered that the body may in fact be producing creatinine in excess.“
This is just one example of a string of such case reports that perpetuate the mistakenly negative effects of protein and creatine supplementation.
Muscle Mass and Creatinine
Increased muscle mass is also correlated with increased serum creatinine. More muscle mass means more storage capacity for creatine, and therefore increased supply and use of creatine phosphate. This leads to higher creatinine levels.
The CKD guideline development group noted that “serum creatinine is correlated with muscle mass and therefore the estimation of GFR using prediction equations in people with extremes of muscle mass is subject to inaccuracy. In those with increased muscle mass, GFR will be underestimated and in those with reduced muscle mass GFR will be overestimated.“
This is particularly relevant to high-level lifters, bodybuilders, powerlifters, athletes with above-average muscle mass, and potentially even just those in the general population training for aesthetic reasons.
There is research exploring kidney function in strength and power athletes on high protein diets with no evidence that they are at greater risk of kidney disease or losses of kidney function.
Creatinine contribution from increased muscle mass alone may or may not be significant enough to flag a false kidney injury. In combination with other factors such as creatine supplementation and a high protein diet – it is worth considering in the wider scope of whether or not eGFR is giving an accurate representation of kidney health.
As we looked at earlier, the MDRD equation which uses creatinine to determine eGFR may not be the most accurate. Other useful tests examining kidney function or damage include the albumin-to-creatinine ratio (ACR) or the serum cystatin C-based equation may be reliable alternative testing methods to assess GFR and kidney function. Serum albumin can also be used as a marker of kidney health.
What did you learn?
Overall the weight of evidence does not support the narrative that high protein diets damage the kidneys or increase the risk of kidney disease unless the kidneys already have an underlying pathology.
In the case of existing renal disease, depending on the staging of the disease, reducing protein intake may help slow down the rate of disease progression.
It is also worth considering the positive impacts and uses of high protein diets. Recognised benefits include increased lean body mass, retention of lean mass in the context of weight loss, increased satiety and usefulness in weight-loss diets. High protein diets can even aid in blood glucose control.
In reviewing the body of evidence for this blog post, I came across this quote from a paper in Nutrition and Metabolism. The paper discussed low protein diet recommendations for chronic kidney disease, and I particularly liked this quote:
“It is important to note that these recommendations are not indicated for individuals with normal renal function nor are they intended to serve as a prevention strategy to avoid developing CKD. Despite the clarity of these guidelines, their mere existence has resulted in concern regarding the role of dietary protein in the onset or progression of renal disease in the general population.“
If you’re healthy, there is no evidence to show that a high protein diet will negatively affect this. If you do have existing kidney issues (you are already likely to be seeing one – but if not), it is worth seeking specialised advice from a well-qualified practitioner!