There is a lot of technical language around IgAN and it can seem confusing and overwhelming when receiving a diagnosis for yourself or a loved one. You may have many questions regarding what it is, how it effects your body, how you got it, and the treatment course that may be available to you.
The causes of IgAN are becoming increasingly understood with research and developments in potential treatment at an all time high. However, more research is still undergoing about this disease and its treatments. For unknown reasons, patients with IgAN create a poorly glycosylated (Protein glycosylation helps in proper folding of proteins, stability and in cell to cell adhesion commonly needed by cells of the immune system), form of the antibody IgA (IgA1) that circulates in the blood in high quantities. The body’s immune system recognizes this IgA1 as foreign and produces antibodies against it (anti-IgA1 antibodies). IgA1 and anti-IgA1 antibodies form immune complexes with each other and complement proteins in the blood.
These circulating immune complexes deposit in the glomeruli (a cluster of nerve endings, spores, or small blood vessels, in particular a cluster of capillaries around the end of a kidney tubule, where waste products are filtered from the blood), causing inflammation and damage. Because of this immune complex mechanism, IgAN is classified as an autoimmune disease. Further damage allows red blood cells and proteins to pass through the damaged filter into the urine.
Now that we know what IgAN is and how it effects the body, you may be curious about the origin of the disease in the body. There is evidence to suggest that genetic factors play a role in IgAN. It has been suggested that IgAN is has many genes it effects and possibly environmental factors that contribute to an individual’s risk of developing the condition.
IgA Nephropathy might be suspected when a patient has bloody (e.g., tea- or cola-colored) urine following a respiratory tract illness such as a sore throat or a cold. Laboratory tests will determine if there are abnormal levels of protein (proteinuria) or blood (hematuria) in the urine and will measure the levels of protein, cholesterol, and wastes in the blood. The glomerular filtration rate (GFR), which determines how well the kidneys are filtering wastes from the blood, may be low in advanced stages of the disease. Although a doctor may suspect that their patient has IgAN based on family or clinical history, physical exam, and urine and blood tests, a kidney biopsy is required for a definitive diagnosis of IgAN.
In its early stages, IgAN is often asymptomatic. However, as the disease progresses, the most well-known life-affecting symptoms of IgAN are edema (excess of watery fluid collecting in the cavities or tissues of the body) and fatigue. Such fatigue can make daily functioning impossible. The severity of the edema is correlated to the amount of proteinuria, and often worsens as the disease progresses.
The most common clinical presentation of IgAN is visible blood in the urine alongside or following an upper respiratory infection. Some patients with established IgAN may also experience blood in the urine and other symptoms as flares when they have infections or even after exercise. Some other symptoms include low-grade fever or flu-like symptoms, flank pain ranging from a dull ache to debilitating spasms, and myalgias.
There are currently no disease-targeted therapeutics approved for the treatment of IgAN. The major option available for current treatment is glucocorticoids (Prednisone). Some patients may also be prescribed a cholesterol-lowering drug (statin) to lower the risk of developing cardiovascular disease. Diet modifications such as salt reduction or the addition of omega-3 fish oil are also commonly prescribed. Therefore, at this time, treatment for IgAN is largely nonspecific and supportive, often with side effects from Prednisone.
In the last decade, understanding of IgAN has increased and there are several treatments in development at pharmaceutical companies. There are currently 25 planned, ongoing, or completed Phase 2 and 3 clinical trials in the U.S. that cover a variety of potential mechanisms of action showing positive signs for effective course of treatment in the next few years.