IgA nephropathy is one of the most common kidney diseases aside from disorders and complications related to diabetes or high blood pressure. In most cases, individuals with IgA nephropathy may not experience symptoms until their late teens to early thirties depending on the rate of damage to the kidneys. IgA nephropathy is twice as common in men than women, and is more prevalent in Asian and European populations while rare in African populations. Long term cases of kidney damage, such as cases of IgA nephropathy that extend over 10-20 years, can cause end-stage kidney disease (ESRD). Instances of IgA nephropathy resulting in ESRD occur in about 20-40% of adults with IgA nephropathy and only about 5-10% of children.

As IgA nephropathy is an autoimmune disease, it is caused by the body’s immune system targeting its own processes and tissues. This produces and releases an overabundance of IgA protein antibodies into the bloodstream to bind to threats and target them for removal or destruction. Individuals with other autoimmune disorders or diseases may be more likely to develop IgA nephropathy. Evidence suggests that individuals with liver diseases such as cirrhosis, chronic hepatitis B and C infections, celiac disease, and bacterial or viral (such as HIV) infections may be more susceptible to IgA nephropathy. 

Individuals with IgA nephropathy express a special type of IgA antibody that contains lower levels of carbohydrates. This difference in structure appears different to the body, and can cause this type of IgA to be targeted by the body’s other antibodies in the immune system. These antibodies form clumps around IgA, which can become lodged in the kidney’s glomeruli and cause inflammation and damage. It is currently unknown as to why this altered version of IgA is expressed, but it is hypothesized that respiratory and intestinal infections can trigger an out-of-control immune response and produce this form of IgA. 

Further research is needed to determine the relationship between IgA nephropathy and genetics. There is evidence of a potential genetic role due to the prevalence of the disorder in some populations over others, a familial inheritance in an autosomal dominant pattern with incomplete inheritance, and the expression of the altered version of IgA in individuals with the disorder. In autosomal dominant inherited disorders, a mutated gene need only be on one chromosome to have an effect on the offspring. This can be inherited from only one parent’s genetic material if they carry the mutated gene. Incomplete inheritance refers to instances when some individuals with the affected gene express the disease trait and some do not. More information is needed to establish the genetic likelihood of developing IgA nephropathy.

The progression of IgA nephropathy differs from person to person, with most starting to experience symptoms of kidney problems between their teenage years to early thirties. The symptoms of these kidney problems may include the following:

• Hematuria - blood in the urine, sometimes visible, other times only detected by medical tests

• Albuminuria/proteinuria - large amounts of protein, more specifically the protein albumin, found in the urine; excretion of albumin reduces the blood’s ability to absorb water from surrounding tissues, causing swelling in the legs, feet, and/or ankles; foamy urine can indicate proteinuria

• Other complications associated with this disease may arise due to reduced filtration of waste out of the blood

1. High blood pressure

2. Kidney failure (acute meaning all at once, or chronic meaning slowly over time)

3. Swelling

4. High cholesterol

5. Heart or cardiovascular problems

6. IgA vasculitis - buildup of IgA in the blood vessels can cause inflammation, restricting blood flow to vital organs and tissues

Upon symptoms related to kidney problems and/or an analysis of medical and family history, a health care provider may conduct tests for different kidney disorders including genetic and genomic diseases. Diagnostic tests can conclude that the symptoms an individual is experiencing are due to a complication in the kidneys. Only a kidney biopsy, the removal and examination of a portion of the kidney, can determine the cause of the kidney disorder and diagnose the individual with a specific disorder, such as IgA nephropathy.

The diagnostic tests for IgA nephropathy focus on the status of the kidneys and then aim to determine which disorder is the cause of their dysfunction. 

• Physical exam – checking an individual’s blood pressure, signs of swelling, and assessing an individual’s symptoms

• Urinalysis – check for blood or protein(s) in the urine

• Blood tests – check for cholesterol, protein, and waste levels in the blood; higher levels than normal indicate a problem in kidney filtration

• Estimated glomerular filtration rate (eGFR) – blood test assessing how much blood the kidneys are capable of filtering every minute

• Kidney biopsy – removal of a small piece of tissue from the kidney to examine glomeruli for IgA deposits and signs of damage

Treating IgA nephropathy involves relieving the symptoms and preventing end-stage renal disease (ESRD) as a result of extensive damage to the kidneys. Some of these treatment options include:

• Controlling/lowering blood pressures – angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs)

• Diuretics – removal of excess fluid causing swelling

• Steroids – manage immune response, lower kidney inflammation

• Statins – lower cholesterol and stress on kidney filtration

• Tonsillectomy – the removal of an individual’s tonsils may improve their prognosis with IgA nephropathy. Based on the hypothesis that abnormal levels of IgA or altered IgA may be released as a result of respiratory infection, removal of the tonsils may prevent the production of undergalacosylated IgA.

• Helpful diet management: limiting sodium, decreasing amount of liquid ingested, foods low in saturated fat and cholesterol, not smoking, diet, and exercise

An individual’s prognosis with IgA nephropathy differs on a case-by-case basis. IgA nephropathy is usually a slowly progressing disorder of the kidneys that may not be recognized and diagnosed until later in life. Some individuals’ conditions may improve, either as a result of treatment, lifestyle changes, or other unknown factors. Other individuals may manage their symptoms and protect against further kidney damage with current treatment options. Left unchecked without treatment, IgA nephropathy leads to kidney damage. Eventually, long-term damage to the kidneys can lead to end-stage kidney disease (ESRD) which causes kidney failure and may require a kidney transplant or dialysis.

Antidote is conducting a clinical trial and seeking willing and qualified participants with IgA Nephropathy: https://antidote.me/prescreener/s/en-US/iga_nephropathy-186?utm_source=RareShare&utm_medium=partner&utm_campaign=E186&utm_content=advocacy

1. Feriozzi S, Polci R. The role of tonsillectomy in IgA nephropathy. J Nephrol. 2016 Feb;29(1):13-9. doi: 10.1007/s40620-015-0247-4. Epub 2015 Nov 18. PMID: 26582216.

2. Wyatt RJ, Julian BA. IgA nephropathy. New England Journal of Medicine. 2013;368(25):2402–2414.

3. https://www.niddk.nih.gov/health-information/kidney-disease/iga-nephropathy#:~:text=IgA%20nephropathy%2C%20also%20known%20as,such%20as%20bacteria%20or%20viruses.

4. https://www.mayoclinic.org/diseases-conditions/iga-nephropathy/symptoms-causes/syc-20352268

5. https://www.kidney.org/atoz/content/iganeph

6. https://my.clevelandclinic.org/health/diseases/5990-iga-nephropathy