High dietary protein effects on kidneys 

WRITTEN BY NATALIA M. KASSIN

High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria.  

Kidneys play multiple roles in keeping us healthy, and their main one is removing waste from the body. They also remove excess water from the tissues of the body, manufacture and excrete urine, release hormones that help regular blood pressure, and play a role in bones, muscles, and other tissues to function correctly.

The recommended daily allowance for protein intake is 0.83 g/kg per day and is calculated to meet the requirements of 97%–98% of the population. By most definitions, a high-protein diet will fall between 1.2 and 2.0 g/kg per day. Data from the NHANES show that the current average protein consumption in the United States is estimated to be approximately 1.2–1.4 g/kg per day, which is higher than the recommended amount.

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with—and even without—impaired kidney function. A continuing glomerular hyperfiltration caused by a high-protein diet may lead to kidney damage through multiple pathways over time.

In the United States, >60% of the population meets the criteria for being obese or overweight. Low-carb, High-protein diets have been heavily promoted in the media as an effective means for weight loss, health, and overall appetite control. However, a high intake of dietary protein, especially animal protein, may lead to higher levels of urea and other nitrogenous waste products, having detrimental effects on kidney function and long-term health.

Kidney damage from high protein can be accelerated by dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. PMID: 32669325

 The reason some long-period observational studies have not shown an association between a high-protein diet and kidney function is most likely due to the balancing effects of hyperfiltration and kidney damage from hyperfiltration. For example, we can use a clinical trial on the Atkins diet with protein around 30% (total energy intake) versus a control diet with 15% protein. In 12 months, participants in the Atkins diet had a rise in creatine, suggesting hyperfiltration. Yet, the differences in creatinine clearance between both groups were reduced after 24 months. This may indicate that the short-term increase of glomerular filtration rate (GFR) with high protein intake may be followed by a decline in GFR over time due to renal injury. A continuing hyperfiltration caused by hypertension in the kidney from dealing with a high-protein diet may lead to kidney damage and disease, as well as proteinuria and albuminuria.

Plant vs. animal protein

There is a strong connection between the type of protein and kidney disease occurrences. The Atherosclerosis Risk in Communities Study, as well as the Singapore Chinese Health Study, showed that those consuming processed/red meat have an increased risk for the disease. Meanwhile, replacing one serving of red meat with a plant protein reduced the risk of CKD by 31% to 62.4%. The suggested reason behind it was the rise in blood pressure that happened with animal protein. Furthermore, studies have shown that animal protein produces less favorable and more imbalanced gut microbiome by means of its pro-inflammatory ammonia and sulfur content. All this may result in reduced kidney function, causing inflammation and oxidative stress to increase in the body. 

Uric acid (urea)

High dietary intake of protein may lead to higher levels of urea and other nitrogenous waste products. 

Uric acid is the waste product of purine metabolism that’s created when the body breaks down purines. Purines are also produced by the body, but dietary purines, especially animal proteins, can significantly contribute to its total amount. 80% of purine sources are produced by our body (endogenous), but some scholars believe that dietary purines may disturb the homeostasis of purine metabolism and be converted to endogenous purine. PMID: 23089274

Uric acid exists mostly as a urate. Normally, most daily uric acid disposal occurs via the kidneys eliminating 2/3rd of it, and the GI tract takes care of the rest. Hyperuricemia happens if too much uric acid stays in the body, and it is a key risk factor for the development of gout, kidney dysfunction, hypertension, hyperlipidemia, diabetes, and obesity. Hyperuricemia can happen because of increased uric acid production, reduced kidney excretion, or a combination of the two. When high uric acid levels are in the blood, deposits of urate crystals occur in the joints and kidneys. Another source of protein-derived toxic compounds, such as indoxyl sulfate, comes from the bacterial fermentation of proteins in the intestine. It has been extensively studied, and it is associated with anxiety, vascular and kidney diseases. PMID: 26239363 PMID: 34697401

Nitrogen is an essential element present in all amino acids. Renal nitrogen excretion consists almost completely of urea and ammonia, and the production of urea is closely related to the amount of protein eaten. Ammonia is produced from leftover amino groups, and it must be removed from the body. The liver produces several chemicals (enzymes) that change ammonia into a form called urea, which the body can remove in the urine. If this process is disturbed, ammonia levels begin to rise.

Several studies have shown that high dietary protein intake is associated with higher BUN concentrations- (blood urea nitrogen test to measure the amount of urea nitrogen in your blood). A study examined 24 healthy young men who consumed either a diet with a high level of protein (2.4 g/kg per day) or a diet with a normal level of protein (1.2 g/kg per day) over 7 days for each diet. The BUN concentrations were significantly higher during the 7 days when they consumed a high protein diet. The results demonstrate that even a short-term diet in healthy adults can have adverse renal effects, altering kidney blood flow and excretion of uric acid, sodium, and albumin. BUN, serum uric acid, glucagon, natriuresis, urinary albumin, and urea excretion increased significantly with the high protein diet. PMID: 19812175

Studies have shown a proportional reduction in urea generation with dietary protein restriction. PMID: 25078422 One theory holds that high circulating BUN levels generate reactive oxygen species, leading to increased oxidative stress, inflammation, endothelial dysfunction, and cardiovascular disease. PMID: 32669325

The high number of patients with kidney disease dying from cardiovascular issues is attributable in large part to endothelial dysfunction. Cyanide is the urea decomposition product that promotes endothelial dysfunction and thus has a role in promoting cardiovascular diseases. PMID: 24940796

High Phosphorus

 Naturally occurring phosphorus is found in protein-rich foods such as meats, poultry, fish, eggs, and dairy products, as well as nuts and beans. Our body absorbs it from animal sources at a much higher rate than from plant sources. Phosphorus is also abundant in processed foods such as spreadable cheeses and canned foods.

 Dietary protein intake is strongly correlated with phosphorus intake. Several large epidemiologic studies have found higher phosphorus levels (even those within the normal range) to be associated with an increased risk of cardiovascular disease morbidity and mortality, even in individuals with normal kidney function. 

Present in nature as phosphate, phosphorus is an essential component of all living organisms, as it plays a role in essential biological reactions. It is found in bones and teeth and in soft tissues and body fluids; reserves of phosphate in the skeletal system act as a buffer to maintain the acid–base homeostasis. Its dietary requirements are easily satisfied as it is present in animal and plant foods, with its most abundant natural source being protein-rich foods. Animal proteins such as meat or fish are more readily bioavailable sources than foods of plant origin, where phosphorus is present as phytate. Only 30-40% of plant phosphorus ends up being absorbed versus 60-80% from animal sources. Phosphorus is also the main component of food additives in processed foods, with this form being most absorbable in 90% and up. Such preservatives are largely used in meat products, processed cheese spreads, sauces, pasta, baked products, and soft drinks. In the USA, adding an injection of phosphorus, salt, and water to meats is allowed in order to enhance the color, flavor, tenderness and extend shelf life. 

A link between high concentrations of serum phosphorus and the increased risk of cardiovascular events and mortality is well documented. NHANEs III Study had 9686 participants aged 20–80 years without diabetes, cancer, or kidney or cardiovascular disease. High phosphorus intake (above ∼1400 mg/d) was shown to be associated with increased all-cause mortality

Elevated phosphorus is connected to endothelial dysfunction, albuminuria, dangerous calcium deposits in the blood, and weakening of the bones. PMID: 24225358

Low protein diets not only lower urea but also reduce phosphorus, which is mainly found in foods with high protein content, such as meat and cheese. Several large epidemiologic studies have found higher phosphorus levels (even those within the normal range) to be associated with an increased risk of cardiovascular disease morbidity and mortality, even in individuals with normal kidney function. PMID: 27401096

Excess phosphate causes the increase of FGF-23 (Fibroblast growth factor 23), a hormone involved in phosphorous and vitamin D homeostasis. In a 10-year-long study among the elderly, it was established that it is associated with all-cause mortality and incidence of heart failure. PMID: 22703926. 

Patients with kidney disease consuming a vegetarian diet with the same amount of phosphorus as meat eaters for a week had lower serum phosphorus levels and decreased FGF23 levels. There was a significant difference between the vegetarian and meat diets. Thus, it is not only the total amount of phosphorus but also the plant-vs.-animal type intake if that plays a significant role. Limiting the phosphate is challenging as the typical Western diet is rich in dairy products and animal proteins. PMID: 21183586

Elevated phosphorus is connected to endothelial dysfunction, albuminuria, dangerous calcium deposits in the blood, and weakening of the bones. Phosphate retention plays a role in arterial and coronary calcification, heart problems such as thickening of the heart valves, and possibly chronic kidney disease progression PMID: 24425728

The REIN trial showed that participants with higher serum phosphate levels had faster progression of kidney disease compared with those who had lower levels. PMID: 21852581

Metabolic acidosis 

Diet has a significant influence on the acid load that needs to be excreted by the kidney to maintain acid-base balance. Modern diets are primarily acid-inducing, whereas, throughout human evolution, more alkalinizing foods were consumed. PMID: 15699220; PMID: 14522740. As a result, humans may not be adequately equipped to deal with current acid-inducing diets, which may contribute to the development of chronic diseases, including kidney disease. 

Metabolic processes produce volatile and nonvolatile acids. Volatile acid is removed through the lungs as CO2 and nonvolatile acid must be removed by the kidney in the form of ammonium and titratable acid. 

It is possible to characterize the foods according to their ability to release acids and bases. The foods that contribute most to the release of acids into the bloodstream are meats (beef, pork, or poultry), eggs, and oilseeds, and the foods that contribute most to the release of bases are fruits and vegetables. If there is an excessive consumption of acid precursor foods and if it occurs for a long time, low-grade metabolic acidosis may become significant and predispose to diseases. Metabolic acidosis can lead to bone mineral loss, muscle wasting, reduced protein anabolism, and increased protein catabolism. All these changes contribute to protein malnutrition and worsen nutritional status. The shift of potassium from the intracellular to the interstitial fluid causes elevated levels of potassium and high phosphate in the blood. Metabolic acidosis also contributes to the progression of kidney disease, and when the kidney functions are impaired, inflammation, acidosis, resistance to anabolic hormones, and defective insulin signaling cause protein wasting, producing loss of muscle mass. Metabolic acidosis increases amino acid oxidation and protein degradation.

Dietary acid might be a risk factor for chronic kidney disease promoting kidney injury and progressive GFR decline. Chronic metabolic acidosis can promote inflammation and fibrosis in an animal model of kidney disease. A diet with high protein intake might lead to metabolic acidosis among patients with advanced chronic kidney disease who have impaired acid excretion and generation of bicarbonate, particularly in the context of protein sourced from animal-based foods. PMID: 31988269

 The standard American diet, where protein is 15% of total energy, produces a dietary acid load of approximately 1 mEq/kg per day, with most of it derived from animal sources such as meats, eggs, and cheeses. By including a higher proportion of foods with natural alkalis, such as fruits and vegetables, a vegan diet is practically acid-neutral. Plant-based foods can be used to reduce both the dietary acid load and the severity of metabolic acidosis. PMID: 23439373  

Metabolic acidosis occurs frequently in chronic kidney disease, and it can be corrected with an early pharmacological administration of sodium bicarbonate but also with a diet rich in fruit and vegetables. A study that investigated the efficacy of a very low protein diet (containing a high quantity of fruit and vegetables) in reducing the acid load in CKD patients saw at 6 and 12 months a significant reduction of both systolic and diastolic blood pressure, plasma urea, phosphate in the blood, urinary sodium, urinary potassium, and urinary phosphate.PMID: 28106712

A low protein intake in patients with advanced nondialysis kidney disease has been shown to decrease the severity of metabolic acidosis. NHANES III data have shown that, among 1486 adult participants with kidney disease, the higher dietary acid load was strongly associated with the development of end-stage kidney disease over a median of 14.2 years. Compared with participants whose dietary acid consumption was in the lowest tertile, those with dietary acid consumption in the highest tertile had triple the risk of incident end stage kidney disaese, even after accounting for differences in sociodemographic, nutritional factors, clinical factors etc.PMID: 25677388

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