Everything you need to know about C3G and IC-MPGN

C3G (Complement 3 Glomerulopathy) and IC-MPGN (Immun complex Glomerulonephritis membranoproliferative) are rare and incurable kidney diseases that have similar symptoms and progression. Although these diseases have many common features, they are recognized as separate disorders due to different causes and underlying mechanisms.

Jump at the main dishes to remember.

What are C3G and IC-MPGN?

C3G and IC-MPGN are two types of membranoproliferative glomerulonephritis, a renal disorder involving inflammation and damage to glomerules (small blood vessels which act as the main filtering units). The glomerules eliminate waste and blood toxins.

C3G and IC-MPGN are triggered by an abnormal immune response which means that antibody deposits accumulate in the glomerules. Previously, the two disorders have been classified as glomerulonephritis membranoproliferative (MPGN), in particular types 1, 2 and 3. However, they are now classified as two distinct entities.

C3G and IC-MPGN have both a high risk of progression to kidney failure. Up to 35% of people affected by one or the other disease develop kidney failure within 10 years of diagnosis.

What causes C3G and IC-MPGN?

C3G

In C3G, C3 refers to the C3 supplement protein, which develops without regulation in this disease. This overproduction of C3G can occur for one of the following reasons:

• Genetic changes: Random mutations or genetic changes can damage the supplement proteins that regulate this system. This causes C3 overproduction, which breaks and is stuck in the kidneys.
• Autoanticorps: A hyperactive complement system can also occur following autoantibodies (abnormal immunoglobulins (IG) which confuse the tissues of your kidney as a stranger. These abnormal antibodies trigger an overactivity.

IC-MPGN

The dysfunction of the complement system that occurs in IC-PGNE is linked to IG and C3 deposits in the renal tissue. It is often associated with other diseases, such as:

• Autoimmune diseases like systemic lupus erythematous or rheumatoid arthritis (RA)
• Chronic infections such as hepatitis B or hepatitis C
• Hereditary disorders
• Immunoglobulin monoclonal depot disease

In rare cases, there is no identifiable cause of IC-PMPM. This condition is called idiopath or primary IC-MPGN.

What are the common symptoms?

The symptoms of C3G and IC-MPGN vary considerably depending on the individual. In many cases, the first symptoms are painless and develop more as renal lesions aggravate.

C3G and IC-MPGN damage your kidneys’ ability to eliminate waste, balance body liquids and regulate blood pressure. Symptoms may include:

• Hematuria (blood in the urine)
• Proteinuria (excess protein in urine)
• Edema (swelling) in your legs, ankles or around your eyes
• DRUSEN (small yellow deposits in your retina)
• Hypertension (high blood pressure)
• Difficulty concentrating and tiring
• Oliguria (less urine production than normal)
• Acquired partial lipodystrophy (abnormal distribution of fat under your skin)
• Nausea and vomiting
• Bone demineralization from the reduced synthesis of vitamin D
• Growth
• High cholesterol

How are C3G and IC-MPGN diagnosed?

The first symptoms of C3G and IC-MPGN are often overlooked. It is not uncommon to obtain a diagnosis when blood and / or protein are detected during a routine urine test.

When C3G and IC-MPGN are suspected, the following tests are used to reach a final diagnosis:

• Renal biopsy: This involves removing a renal fabric sample for a microscope exam. It is considered to be the ordeal to diagnose C3G and IC-MPGN.
• Immunofluorescence: This specialized type of microscopy uses an optical microscope to check the biopsied renal tissues for the accumulation of C3 fragments and immunoglobulin deposits.
• The following diagnostic tests can also be used to determine the renal function and define the stage or the progression of the kidney disease:
• Urine analysis: A urine test detects and measures protein and blood levels in your urine.
• Complete blood number (CBC): A CBC measures the levels of red blood cells, white blood cells and platelets.
• Estimated glomerular filtration rate (EGFR): This blood test measures to what extent your kidneys waste your blood.
• C3 complementary to the complement, including genetic tests: This blood test assesses the system of complement your body. Genetic tests help identify underlying mutations or anomalies in genes.
• Measuring levels of serum creatinine and cytatin C: These blood tests identify the potential secondary complications of a chronic kidney disease.

Processing options

Although several treatments are in clinical trials, there is no treatment approved for C3G or IC-MPGN. Current options involve therapy for support for damage to the slowdown in the kidneys:

Therapies for C3G and IC-MPGN may include:

• Corticosteroids and immunosuppressive drugs: A corticosteroid, like prednisone, used with an immunosuppressant, such as mycophenolate Mofil (MMF), can adjust a hyperactive supplement system.
• Angiotensin– Convert enzyme inhibitors (ECA inhibitors) and angiotensin receptor blockers (ARB): These blood pressure drugs help control blood pressure and minimize protein loss to protect your kidneys.
• Food changes: Management of salt intake, control of protein consumption and reduction of cholesterol can help reduce the load of damaged kidney disease, reduce edema and control blood pressure.
• Powerful Hypola agents: These drugs, which include statins, can normalize the total levels of cholesterol, LDL and triglycerides.
• Glucose Cotransporter-2 inhibitors (SGLT2): These drugs can help reduce proteinuria and normalize glucose levels.
• Even carefully, around 50% of people with C3G or IC-MPGN need renal dialysis and / or kidney transplant in the first 10 years at the start of the disease.
• Renal dialysis: This treatment replaces the normal kidney function by eliminating waste and excess of liquid from your blood.
• Kidney transplant: Although this replaces a damaged organ, it does not heal the underlying cause of the disease. The incidence of recurrence C3G or IC-MPGN in the new organ is high.

Main to remember

• Note the signs of protein or blood in your urine can help early detection of C3G and IC-MPGN.
• Membership of a monitored treatment plan is essential because the risk of progression to renal lesions is high for both diseases.
• Although C3G and IC-MPGN are incurable, support care can help manage slow renal symptoms and renal lesions.