Immunoglobulin A (IgA) nephropathy is a prime example of the interplay of genetics, epigenetics, leaky gut, environment and diet affects and influence the development of kidney disease.

What is IgA?

Immunoglobulins are a large protein structure that is part of the adaptive immune system. There are various types, categorized by a letter and sometimes a number to identify the subclass, for example IgA1and IgA2. For the context of this discussion, we will the focus immunoglobulin A (IgA) without distinction to subclass.
IgA is found in the blood serum, lining of the respiratory (lungs) and digestive (gut) tracts. It is also found in saliva, tears, and breastmilk. Also called an antibody, the body makes IgA and other types of antibodies to help fight off invading pathogens (i.e. bacteria, viruses) and prevent disease. It is one of the first lines of defense against invading organisms from the environment, diet, and toxins.

What is IgA nephropathy?

IgA nephropathy is an autoimmune kidney disease. A trigger causes the immune system to produce abnormal IgA proteins that causes the immune defense to damage the kidney (nephrons). Abnormal IgA immune complex structures are formed, they circulate and filter through the kidney where they are “captured”. Unfortunately, these structures build-up in the kidneys, resulting in inflammation which damages kidney tissues.

What triggers an IgA immune response?

Though there’s some evidence that points to certain heavy metals (like cadmium) as a source of toxicity, the strongest evidence in the literature points to triggers can be classified into the following categories:

  • Food sensitivities/allergies (i.e. gluten, soy, lectins/lipopolysaccharides)
  • Microbial imbalance (known as dysbiosis) in the intestinal tract

Several studies have demonstrated an association between intake of gluten and lectins. One study demonstrated that patients with IgA nephropathy who followed a gluten-free diet for 6 months had a reduction in IgA levels. Studies on Mediterranean people eating a diet rich in gluten-containing foods published as far back as 1986 have suggested a dietary component to kidney disease. Soy is another example of a food antigen that has been associated with IgA nephropathy. However, heavy use of pesticides (glyphosate) in our food sources (especially gluten and soy) may play a role in food-related nephropathy. [bctt tweet=”Heavy use of pesticides (glyphosate) in our food sources (especially gluten and soy) may play a role in food-related nephropathy” username=”inkidney”]
In susceptible individuals, the intake of a dietary trigger leads to intestinal permeability (IP), also known as leaky gut. In fact, research dating back decades has supported a connection between the gut and IgA nephropathy, called the gut-kidney connection. One of the proposed mechanisms, is the development of microbial imbalance (dysbiosis) which leads to bacteria and food proteins “leaking” through the gut barrier, triggering IgA immune response damaging the kidney.

The role of dysbiosis

In the case of IP, the compromised lining of the gut (mucosa) allows abnormal microbes, endotoxins (toxins produced by microbes), or food particles and metabolites to enter the bloodstream.
Furthermore, studies have shown that patients with progressive IgA nephropathy tend to have low number of naturally occurring healthy bacteria in the gut (likeBifidobacterium species) and a high amount of unwanted, or pathogenic, bacteria (likeSterptococceae). Our gut lining cells have complex mechanisms to detect the type of microbes that are present in our gut. There is a consistent link between these mechanisms and the production of an abnormal IgA.

The genetic link to an abnormal IgA response?

Genetics likely also play a role in the risk of developing kidney disease. Researchers have identified genetic variances (also referred to as single nucleotide polymorphisms, or SNPs) linked to IgA nephropathy in a multinational study.
Most of the genes involved in regulating the response and immunity against gut microbes. Interestingly, many of these SNPs associated with IgA nephropathy risk are related to inflammatory bowel diseases (IBD) or with the maintenance of the intestinal barrier. These SNPs lead to abnormal trafficking of IgA and the formation of an abnormal IgA that triggers the body’s immune response.

The autoimmune response, putting it all together

Recall, the presence of abnormal IgA in the blood leads to the formation of protein complexes in response to neutralize the threat. Unfortunately, these proteins end up forming structures that are difficult for our body to eliminate. These complex structures with abnormal IgA end up depositing in the kidney, leading to local inflammation and loss of kidney function.


Now it should be clearer that IgA nephropathy is a classic example of how a combination of genetic, environmental factors, dietary and gut integrity interact to cause disease.
[bctt tweet=”IgA nephropathy is a classic example of how a combination of genetic, environmental factors, dietary and gut integrity interact to cause disease” username=”inkidney”]

Conventional medicine approach

The conventional approaches have failed to find a completely effective treatment for IgA nephropathy. Approaches include conservative control of blood pressure and blockage of the angiotensin-renin pathway, reduction of protein in the urine, and use of immunosuppressive therapy (including steroids and other medications), and fish oil.
More recently, a special kind of steroid that targets the terminal part of the gut (ileum and cecum) is being studied. The hope is that these special steroids will focus on one aspect of the process that leads to the formation of abnormal IgA which is decreasing the immune response in the gut.

Integrative medicine approach

A more integrative approach to IgA nephropathy would personalize treatment to take into account the impact of IP:

  1. Identifying the and eliminating the dietary or environmental triggers that contribute to leaky gut
  2. Assess and address dysbiosis
  3. Capitalize on epigenetic modifications to reduce the expression of SNPs contributing to IgA upregulation.

In combination with evidence-based conventional medicine, this approach targets various mechanisms and complications of the disease and improving outcomes.