Complement 3 glomerulopathy (C3G) are a set of rare kidney diseases that are characterised by complement dysregulation. These diseases present themselves in two patterns: C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). The damage to the kidney tissue presents itself differently in DDD and in C3GN. The C3 refers to a blood protein that plays an important role in immunity and the development of this disease. It results in damage to the glomeruli in the kidney, which help filter the blood. The rarity of this disease (2-3 per 1,000,000 people) allows for a lot of speculation from the medical community which is further elevated by its history. Prior to 2013, this disease was referred to as, ‘membranoproliferative glomerulonephritis (MPGN)’. Due to new findings regarding the microscopic appearance of the glomeruli, the name and definition changed to C3G.
sourced from: https://www.nature.com/articles/s41581-018-0107-2
The Cause
First things First, what is the Complement system? It is a part of the immunity system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation and attack the pathogen’s cell membrane. This system consists of a collection of proteins in the blood.
The problem arises when the complement system is abnormally activated. This causes the normal complement protein C3 to breakdown and its product to accumulate in the kidney. This hence results in a domino effect where glomeruli filtering becomes inefficient, urine production is reduced and toxins buildup in the blood.
Reasons why the complement system can be abnormally activated:
Lack of control: due to lack of regulatory proteins in the system, the system acts uncontrollably.
Genetic mutations: genetic changes in the regulatory proteins reduce its ability to control the system
Development of antibodies: prevent the normal regulation of the system. Also referred to as the genetic or acquired drivers of C3G.
Signs & Symptoms
Blood in the urine (hematuria): due to damage in the glomeruli, red blood cells can leak out and change the colour of the urine.
Excess protein in the urine (proteinuria): this results in dark or cloudy urine due to high amounts of protein leaking from the damaged glomeruli.
Swelling (edema): due to buildup of fluid, the eyes can look puffy and the area around the hands, feet and ankle can swell up.
Gout: due to inefficient filtration of uric acid, it can accumulate in the joints and crystalise, causing joint pain.
Less urine production (oliguria): normal urine production is reduced as filtration of blood is reduced.
Hypertension: due to fluid buildup.
Fatigue: wastes and toxins can accumulate in the blood reducing the ability of a person to concentrate.
Tests done to find if C3G is the culprit!
Blood test: to check if complement proteins are normal and buildup of toxins.
Urine test: to see blood or protein.
Glomerular Filtration Rate: to know how efficiently the kidney is removing waste from the kidney.
Kidney biopsy: to see breakdown of products of C3 which can give a definitive diagnosis.
Cure or Treatment?
There is no cure for this disease, unfortunately, but there are ways to slow the process of kidney damage.
Corticosteroids and immunosuppressive drugs: to stop the immune system from attacking the glomeruli
ACE inhibitors and ARBs: blood pressure medications to reduce protein loss and control hypertension.
Diet change: reducing protein and sodium in the diet to lighten the load on the kidneys.
Rare diseases like this one do not have constructive cures or therapies and only have treatments that may or may not work. On top of that, these treatments may not affect every patient the same way and hence are usually a hit or miss. Hence, rare disease organisations are more important than ever to further research to develop effective treatments and eventually cures.
Written by: Svasti Tewari
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