Dietary Oxalate and Kidney Disease: Is Dietary Oxalate Toxic to the Kidneys?

Mentioning a plant-based recipe or a plant food to chronic kidney disease patients often leads to worries about their oxalate contents. The worry focuses on the potential effects of high-oxalate foods on the kidneys or the risk for kidney stones. However, there is a lot of misinformation about dietary oxalate and kidney disease. In this blog, I am going to present the most current evidence and try in particular to answer the question: is dietary oxalate toxic to the kidneys?

What is oxalate?

Before we discuss the effects of oxalate on the kidneys, let’s answer the question: what is oxalate? Oxalic acid (or its ionized form, oxalate) is a simple chemical compound that humans cannot break down. It is essentially, therefore, a waste product that the body must eliminate. The kidneys are the major site of that elimination.

Despite its chemical simplicity, oxalate is actually very complex to study and understand. Most of the circulating oxalate is formed in the liver from the oxidation (the chemical combination with oxygen) of a substance called glyoxylate. Glyoxylate has two main sources. One is from carbohydrate metabolism and the other is from the degradation of collagen and protein.

While the human body cannot break down oxalate, it can use its precursor, glyoxylate, by converting it into the amino acid glycine. Vitamin B6 is a major cofactor in this conversion. This makes oxalate and glyoxylate a central link between the metabolic pathways of amino acids and carbohydrates.

Metabolism of ascorbic acid (vitamin C) can also lead to the formation of oxalate (we will discuss this in detail in a future blog). Finally, it has been noted recently that oxalate can be generated from the breakdown of proteins, carbohydrates, or lipids that have been damaged by oxidative stress or elevated blood sugars (see figure). Oxidative stress is an imbalance between free radicals and antioxidants. The body needs some oxidative stress, but too much of it can cause problems.

All of the above pathways are responsible for 80% of oxalate produced by the body and excreted in the urine.

 

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Dietary oxalate sources

Dietary sources of oxalate include green leafy vegetables, different nuts, seeds, and roots, cocoa, and tea. Healthy individuals usually consume 100-200 mg of oxalate per day. The small intestine is the primary site for oxalate absorption. But it is important to realize that not all consumed oxalate ends up getting absorbed. This is because of three factors:

  1. Oxalate tends to bind with calcium and magnesium in the diet to form insoluble complexes that end up excreted in the stool.
  2. The gut microbiome contains bacteria that break down and use oxalate for energy. Probiotics containing Oxalobacter formigenes and others decreased serum oxalate levels. Diets that are high in fiber are also associated with a decrease in intestinal oxalate absorption.
  3. Finally, the gut can excrete oxalate.

In fact, studies have shown that in healthy individuals, only 8% of the average daily intake of oxalate is absorbed.

Oxalate production in the body

 

 

Elevated oxalate in the urine – hyperoxaluria

When there is excessive oxalate in the blood, the excretion of oxalate in the urine increases. This is called hyperoxaluria. Hyperoxaluria is usually defined by the excretion of more than 40-45 mg of oxalate per day in the urine.

There are two major causes of hyperoxaluria:

  • Genetic (primary hyperoxaluria). Here, there are mutations in enzymes that increase the production of oxalate by the liver.
  • Secondary or enteric hyperoxaluria. This occurs in patients with inflammatory bowel disorders, malabsorption, or certain bariatric surgeries. In this type of high urine oxalate, the fat that is not absorbed by the gut binds dietary calcium. This leaves soluble oxalate more available for absorption into the systemic circulation, which increases levels of oxalate.



Oxalate and Kidney disease

Oxalate effects on the kidneys

Unquestionable data shows that patients with decreased kidney function tend to have higher levels of oxalate. In fact, oxalate excretion decreases with decreasing kidney function (as measured by glomerular filtration rate, GFR).

Oxalate has been found to be inflammatory to the proximal tubules of the kidneys and it leads to interstitial fibrosis (scarring). Proximal tubules are the part of the kidney cell that recycles (reabsorbs) the molecules that the kidneys are filtering.  Oxalate also binds to calcium systemically and deposits in tissues causing fibrosis in the heart and hardening of blood vessels.



What causes kidney stones?

We discussed the different types of kidney stones in a previous blog. Calcium oxalate stones are the most common types of kidney stones. Excessive oxalate in the urine can also bind calcium, forming kidney stones.

In short, excessive urinary oxalates can cause kidney stones, and oxalate and kidney stones are something that kidney disease patients need to be cautious about.

 

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Is dietary oxalate toxic to the kidneys?

Proponents of restricting dietary oxalate tend to restrict many of the plant sources of oxalate mentioned above. It is true that there are animal models of dietary oxalate-induced kidney disease. However, these animals were fed a massive amount of oxalate and a calcium-free diet. On the other hand, it is critical to emphasize here that there are no real outcome studies that demonstrated the efficacy of a low-oxalate diet on the progression of kidney disease or even kidney stones. In fact, limiting dietary oxalate may lead to adverse outcomes such as these:

  1. It may be harmful to the diversity of the gut microbiome and lead to dysbiosis. The gut microbiome is the population of microorganisms that reside in the gut. An imbalance, where the bad microbes outnumber the good, is called dysbiosis. Dysbiosis can promote kidney disease.
  2. A low-oxalate diet limits foods that have proven benefits in kidney disease, cancer, and cardiovascular disease prevention. Every day, there are new studies confirming the benefit of a plant-based or Mediterranean diet for kidney health.
  3. It decreases the intake of nutritional antioxidants. Oxidative damage is a contributing factor for people with CKD.
  4. It reduces the quality of consumed nutrients that may contain magnesium, fiber, and alkali, which are beneficial for health.
  5. It does not address the root cause of kidney disease or calcium oxalate stones.
  6. It does not address the bigger portion of oxalate produced from animal protein and collagen by the liver, which may not be as healthy as plant-based sources.

The bottom line on oxalate and kidney disease

Oxalate levels increase with advancing kidney disease and can lead to inflammation and its faster progression. Yet, going on a low-oxalate diet is not an evidence-based recommendation for chronic kidney disease patients and could cause more harm than good. Consuming a well-balanced, whole-food, plant-dominant diet that is rich in calcium, magnesium, probiotics, and prebiotics (fibers) is more important to slow the progression of kidney disease and improve its outcomes. These dietary changes should be done under the care of an integrative team comprised of a nephrologist and dietitian/nutritionist and a coach. Join us for free to learn about the integrative medicine approach to kidney health.