Complement 3 glomerulopathy (C3G) and immunoglobulin A nephropathy (IgAN) kidney diseases are rare glomerular conditions that involve dysfunction in the body’s immune system.
Chronic kidney disease (CKD) describes kidney damage that occurs gradually over time. It eventually affects how well the kidneys perform functions like filtering blood and maintaining the body’s electrolyte balance.
There are many types of kidney diseases. Complement 3 glomerulopathy (C3G) and immunoglobulin A nephropathy (IgAN) are two rare types that develop from underlying immune system activity.
C3G and IgAN kidney diseases are separate conditions, but they’re both rare forms of CKD that involve damage to the glomeruli. The glomeruli are the part of the kidney responsible for filtering blood.
C3G kidney disease
Dysfunction in the complement system causes C3G kidney disease.
The complement system, also called the complement cascade, helps your body fight infections like bacteria and viruses.
The complement system makes it easier for immune cells to find and destroy pathogens and control the overall immune response.
In C3G kidney disease, dysfunction of the complement system creates a large amount of the protein C3. C3 is a core component of the complement cascade. After an immune response, the kidneys filter it out of the body.
Too much C3 in the bloodstream can overwhelm the kidneys’ glomeruli, where blood is filtered under pressure. Rather than being completely expelled, the excess C3 accumulates into dense deposits that injure the glomeruli. This prevents proper blood filtration and decreases your glomerular filtration rate (GFR).
Two subtypes of C3G exist:
- Dense deposit disease (DDD): an electron-dense presentation of C3 deposits
- C3 glomerulonephritis (C3GN): more widespread C3 deposits that are not as electron-dense as those in DDD
IgAN kidney disease
Immunoglobulin A nephropathy (IgAN) kidney disease, known as Berger disease, also involves buildup inside the glomeruli.
In IgAN, clumps of IgA antibodies damage the glomeruli. IgA antibodies are a type of antibody the white blood cells make during a typical immune response.
For reasons that are still unknown, amounts of IgA accumulate in the glomeruli rather than the kidneys filtering them out.
For some people, IgA deposits in IgAN trigger the body’s complement cascade, creating more deposits of C3, similar to those seen in C3G.
C3 deposits aren’t present in all cases of IgAN. However, their involvement in IgAN’s progression can vary from person to person.
C3G and IgAN are immune-mediated conditions. This means underlying immune system dysfunction is involved in their pathology.
They’re sometimes referred to as autoimmune conditions. But in typical autoimmune disorders, the immune system directly attacks healthy tissue because it’s unable to distinguish it from a pathogen.
Immune-mediated conditions include autoimmune diseases. However, “immune-mediated” is an umbrella term that also describes conditions where immune system dysfunction indirectly causes disease processes, like in C3G and IgAN.
In addition to being immune-mediated disorders, C3G and IgAN are also both:
- glomerular disorders
- involve inflammatory responses that lead to kidney damage
- are progressive
- may involve genetic abnormalities that cause immune dysfunction
Although they’re separate diagnoses, C3G and IgAN have similar symptoms of CKD.
These symptoms include:
- hematuria, or blood in the urine
- proteinuria, or protein in the urine
- cloudy urine
- swelling, also known as edema, in the legs and other parts of the body
At the core, C3G and IgAN are as different as they are similar.
C3G, for example, may be more closely tied to genetic variants that affect the complement cascade directly. IgAN is thought to involve a complex mixture of environmental factors and genetics that predispose you to IgAN.
The range of symptoms between these conditions also varies. C3G can involve a larger variety of signs and symptoms. IgAN predominantly involves classic CKD symptoms, like hematuria.
According to the National Kidney Foundation, C3G may also involve symptoms of:
- low urine output, known as oliguria
- high blood pressure
- drusen, an eye condition involving protein and fat deposits in the retina
- acquired partial lipodystrophy, which is abnormal loss of body fat deposits
If you’ve received a diagnosis of C3G or IgAN, learning the medical terminology associated with your condition can help you gain a broader understanding of the diagnosis.
|acquired partial lipodystrophy||the abnormal breakdown of fat deposits in the body; also known as Barraquer-Simons syndrome|
|autoimmune disease||a condition in which the immune system mistakenly targets healthy cells as if they were pathogens|
|C3 glomerulonephritis||a subtype of C3G that’s more widespread and not as electron-dense as DDD|
|dense deposit disease (DDD)||a subtype of C3G identified by the presence of electron-dense C3 deposits|
|drusen||an eye condition caused by a buildup of complement proteins and fats in retina|
|edema||fluid accumulation in the tissues of the body, mainly in the extremities|
|glomerular disease||diseases specifically affecting the glomeruli|
|glomerular filtration rate (GFR)||a measurement of the rate of blood flow through the glomeruli|
|glomeruli||clusters of blood vessels within the kidneys that act as pressurized filters for the blood|
|gout||an arthritic condition caused by crystal accumulation in the joints|
|hematuria||the presence of blood in the urine|
|immune-mediated disease||an umbrella term for conditions caused by direct or indirect underlying immune system dysfunction|
|immunoglobulin A||a type of antibody made by the white blood cells in a typical immune response|
|oliguria||decreased urine output|
|proteinuria||the presence of excess protein in the urine|
C3G and IgAN are glomerular disorders that cause CKD.
They are both considered immune-mediated conditions with similar symptoms, but different types of glomerular buildup define these diagnoses.