- How the illness affects people
- What can be done about it?
- Other peoples’ experiences
- Patient support group
- How the disease works
- What’s new? Opportunities for research and development
How the illness affects people
Membranous Nephropathy (MN) affects men twice as often as women and is more common in adults between the ages of 40 and 70. It develops slowly, over a number of years, and people may not realise they have the disorder. Some are identified simply because they are found to have a lot of protein in their urine after a routine test.
The first thing a person may notice is that their urine appears very frothy, like the head on a pint of beer. This is due to excess protein in the urine. Normal urine has only traces of protein in it, but in MN the kidneys leak a lot of protein into the urine.
Patients often have a puffy face, particularly with swelling of the eyelids first thing in the morning. The tummy may also feel distended and the ankles are swollen, especially in the evenings. These symptoms are due to extra fluid being retained in the body by the kidneys. These are the first symptoms in 8 out of 10 people diagnosed with MN.
These complaints will often trigger a visit to the GP. Simple blood and urine tests will confirm the presence of a nephrotic syndrome. GPs may also find that the patient has high blood pressure.
In people with the severest form of MN or in those who delay seeing their doctor, the disease may have already caused additional damage to the kidneys. This could limit the kidney’s ability to get rid of waste products via the urine so that they build up in the patient. Even so there are few additional symptoms unless kidney failure is advanced. Patients may feel more tired than usual.
What can be done about it?
A first step is to get the right diagnosis. Once the GP has identified that the person has ‘nephrotic syndrome’ or perhaps just heavy proteinuria, the patient will be referred to a kidney specialist. A range of disorders can present in a similar manner and additional blood tests can help to exclude some of them. However the precise diagnosis can only be made with a kidney biopsy. Characteristic features are found that confirm the diagnosis of MN.
There is a lot that can be done to improve MN pateints’ wellbeing even if it does not address the root cause of the problem. Most patients will be treated with medicines called Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARB). These drugs were originally designed to treat high blood pressure. However they also reduce the loss of protein in the urine and allow the level of albumin in the blood stream to improve. Diuretic medicines that get rid of excess fluid from the body can help control swelling. Angiotensin antagonists/inhibitors and diuretics tend to work together, amplifying each other’s effects.
Nutritional support helps to strengthen the bones and muscles. Attention to detail is important and decisions have to be tailored to each person’s needs. Patients with MN need to be closely monitored.
Between 25%-40% of MN patients improve spontaneously.
MN is a disorder of the immune system (see How the disease works). In patients who do not improve spontaneously, treatment with a wide range of immunosuppressive drugs may be used. There is a lack of good quality trial information about them, particularly the newer medicines such as Rituximab and Benlysta. Responses to these medicines can vary and it is not easy to predict the outcome.
If kidney damage progresses, kidney replacement therapy becomes necessary. This can be undertaken by dialysis or a kidney transplant. In some patients MN can recur in the transplanted kidney. Currently it is not possible to predict which patients are at risk of this. Overall, a kidney transplant remains the best option for most MN patients who have lost kidney function.
Other peoples’ experiences
I have MN also called glomerulonephritis. I had never heard of either before 1998 when my doctor sent me to the main hospital for a second opinion. At first I felt that it was something I caught. I lived a healthy lifestyle where I didn’t smoke or drink but I did have a lot of salt and sugar in my meals, hence the high blood pressure (all has changed now). When I take the ten or so tablets I’m on I feel fine and know the doctors are doing everything they can to keep the kidneys going, although they are only working at about 9%. I hope that they may find a kidney donor soon and I can get all the energy back I had before this all happened.
Living with this disorder has meant I have to miss out on some things I love, like grapefruit and bananas. It has made me look at what I do eat now and how much salt it has in it. My hair and skin has changed as the kidneys do a major function in the body to keep these things looking and feeling good (never knew that).
I shall more than likely be going on to dialysis soon and not looking forward to this as I will have to give up work during the time I’m on the machine. It’s for the good I suppose.
Maybe one day this illness will be a thing of the past and we will look back and say ‘do you remember membranous nephropathy?’
Patient Support Group
How the disease works
One task of the kidney is to filter the plasma, the watery fluid of the blood stream. It does this in specialised microscopic blood vessels known as glomeruli. Each kidney can have up to a million of them. These filters allow water and small molecules to leave the blood plasma to be processed by the tubules of the kidney. Larger molecules, like albumin, stay behind in the blood. Albumin is the most common protein dissolved in plasma. If you remember that an egg white is chicken albumin, you will get a picture of human albumin which is very similar.
In MN the filters allow plasma albumin to leak across and end up in the urine where it is wasted. The body tries to make extra proteins but cannot keep up with the losses. Proteinuria means protein in the urine.
The filtration occurs across a special membrane, the glomerular basement membrane. Looked at under a microscope this membrane appears thickened in membranous nephropathy, which is how the condition originally got its name. The thickening is because extra membrane is made around little deposits of antibody.
Antibodies are part of the immune system that defends against infection. They are specialised proteins that recognise very precise chemical patterns on germs, stick to them and help to get rid of them. Sometimes antibodies are produced that target normal tissues by mistake and cause disease. These are autoantibodies (antibodies against the self). Diseases caused this way are autoimmune diseases.
Membranous nephropathy is an autoimmune disease. Recent work has indicated that in three quarters of patients there is an autoantibody that targets a protein known as PLA2R (phospholipase A2 receptor). This receptor occurs normally on the cell right next to the glomerular basement membrane, the podocyte. Podocytes are responsible for making and maintaining the glomerular membrane. They also regulate the filtration process. Studies are ongoing to see if the antibody, anti-PLA2R is the primary cause of damage to the filters and whether measuring these antibodies can be used as a monitor of disease activity.
The events that trigger MN are unclear. In the majority of patients the cause is unknown. In this case the disease is called ‘Idiopathic MN’. Rarely, other diseases lead to the development of MN. For example infections like viral hepatitis, autoimmune conditions like Lupus Erythematosus, Rheumatoid Arthritis, and some cancers. Occasionally drugs can induce it. When MN develops in association with another condition it is described as ‘Secondary Membranous Nephropathy’. Patients with MN are routinely investigated to see if there is a possible underlying cause.
What’s new? Opportunities for research and development
We have probably learnt more about this disease in the last 5 years than we did in the previous fifty. The breakthrough came in 2009 when the antibody likely to be responsible for the disease and its target (PLA2R) were identified. This antibody occurs in 72-75% of MN patients but not in other people. UK scientists developed and made available the first rapid method of measuring levels of anti-PLA2R antibodies in patients.
Further work in the UK has identified genetic factors that help explain why some people are susceptibility to MN. The results of this extend our understanding of MN as an autoimmune disease. Ongoing work is being funded by the Medical Research Council (2013-2015), Kidney Research UK (2013-2014) and the European Union (2012-2017) to further understand the disease and seek new ways of treating it. A detailed breakdown of the research questions currently being asked appears in the aims of the Membranous Nephropathy Rare Disease Group page.
The MN Rare Disease Group (RDG) is working with international partners with the aim of finding new and improved treatments and to empower patients. To do this the RDG is registering patients with this condition in the National Renal Rare Disease Registry (RaDaR).The registry will be used to find suitable participants for future research trials into the effectiveness of new treatments.
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