Patients - C3 Glomerulopathy - How C3G Is Diagnosed And Treated

I was sick of seeing hospitals and wanted to have a normal life, so I carried on and worked hard, but it’s not easy.

Initially, C3G may be ‘silent’ with no symptoms and those affected may have no idea they have kidney disease. In many people, symptoms do not appear until the kidneys are badly damaged. In some cases, C3G will only be identified when tests are carried out for other reasons or when symptoms become severe.

There is no one specific treatment for C3G but treatments are available to slow the progression of the disease and treat some of the symptoms associated with it.

+ What are the symptoms of C3G?

“Fatigue is a huge burden. It’s not just kidney pain or the physical symptoms, the wider impact on life meant I couldn’t socialize and felt depressed.”

• blood in the urine (hematuria). This may not be noticed by the patient and only detected when a stick test is carried out
• dark, foamy urine which signifies the presence of excess protein (proteinuria)
• cloudiness of the urine, reflecting the presence of white blood cells
• fluid retention (edema) and swelling of the hands, feet and ankles
• elevated creatinine (this would only be picked up in a blood or urine test)
• high blood pressure
• as kidney function reduces, patients may also experience poor appetite, nausea, fatigue, sickness and weight loss
• the eyes can also be affected: deposits called drusen can build up at the back of the eye.

+ How is C3G diagnosed?

A blood test (a full blood count) is used to assess levels of substances such as platelets and hemoglobin in the blood.

A urine test to see if complement proteins are normal and if there are signs of waste materials building up in the blood.

Glomerular filtration rate (GFR) test to assess how well the kidneys are filtering waste from the body.

Ultrasound scans are non-invasive scans that may be used to examine the size and shape of the kidneys.

Kidney (renal) biopsy is the only way to make a definitive diagnosis of C3G. A small piece of tissue is removed from the kidney using a needle. In most cases, this will be done through the skin (percutaneous needle biopsy). A local anesthetic will be given and a small cut made, through which a needle will be inserted. In the laboratory, a special stain is added to the sample tissue and it is then examined under a microscope to assess what may be causing damage to the kidney. Alternatively, an open biopsy may be carried out when the sample is taken directly from the kidney during surgery.

Key treatment options

There is no one specific treatment for C3G but a number of treatments and supportive therapies are used to treat the problems associated with the disease. Like many kidney diseases, the progression of C3G is variable. In some people with C3G, the disease remains stable for many years but in others it progresses more rapidly. Treatments aim to slow the progression of C3G and keep symptoms under control and many patients respond well to treatments. The type of treatment offered will depend upon the stage of the disease. Over time, many patients can deteriorate as their kidney function declines. About half of patients will progress to kidney failure, at which point dialysis or a kidney transplant will be needed.

Immunosuppressants can result in side effects which were hard to deal with. I lost a big part of myself.

+ Current treatment options

• Medications such as ACE inhibitors or ARBs are often offered to patients with all types of kidney disease. ACE inhibitors are angiotensin-converting enzyme inhibitors and ARBs are angiotensin receptor blockers. They help to lower blood pressure and work to reduce the amount of protein that leaks into the urine, which improves the balance of protein in the body.
• Statins may be offered to patients with high levels of lipids (fats like cholesterol).
• Dietary management may be offered to ensure normal growth in children and to maintain healthy weight in adults. Patients with more advanced kidney disease will be given specific instructions on foods to avoid, for example reducing intake of salt and protein to reduce the load on the kidneys.
• Immunosuppressive agents, such as prednisolone (a steroid), mycophenlolate mofetil (MMF), cyclophosphamide and rituximab, may be helpful in some patients with C3G. They work by suppressing the body’s immune response.
• Plasma exchange is a procedure in which plasma (the liquid part of the blood) is removed from the body and replaced with fresh plasma. The aim is to remove the faulty complement proteins and replace it with ‘healthy’ plasma. A needle is inserted into a vein, the plasma is removed and fed into a special machine where it is processed. A plasma substitute is added and the blood is returned to the vein. The process normally takes a few hours.
• Dialysis about 50% of patients with C3G develop end-stage kidney disease within 10 years of diagnosis and need some form of renal replacement therapy (something which takes over the function of the kidneys). The most common type is hemodialysis. A tube is attached to a needle in the arm, blood is removed and filtered and then returned to the arm via another tube. Dialysis needs to be repeated several times a week. It is carried out in hospital or some patients may be able to perform dialysis at home.
• Transplantation may be an option for some people with C3G. Kidney transplants are performed frequently for patients with all types of kidney disease and can be extremely successful. Unfortunately, in the case of C3G, it does not cure the underlying fault in the complement system and so the disease may re-occur in the transplanted kidney.
• Eculizumab is a monoclonal antibody drug that is licensed to treat two other diseases associated with problems with the complement system. It has been approved in the UK for patients who have had a kidney transplant and have a recurrence of C3G if they meet specific criteria.

+ Are there any new treatments on the horizon?

• Understanding about the causes of C3G has increased greatly in the past two decades and a number of promising new approaches are currently being investigated. Many of these are designed to target the complement system. These include a gene ‘silencing’ therapy that is designed to temporarily block a specific gene’s message that would otherwise trigger an unwanted effect. Pre-clinical and clinical research into these new approaches are underway and have the potential to improve the outlook for people with C3G.

+ Which healthcare professionals are involved in the care of people with C3G?

Once C3G has been diagnosed, most patients will be under the care of a renal (kidney) specialist – known as a nephrologist – and their team. Blood tests and monitoring may be carried out by their family doctor or GP.

Those with drusen (deposits in the eyes) will be referred to an ophthalmologist.

If specific dietary changes are recommended, a dietitian may provide advice on tailored eating plans.

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