IgA Nephropathy
IgA nephropathy under the microscope
What is IgA nephropathy and how did I get it?
IgA nephropathy is the most common form of glomerulonephritis. The prevalence varies throughout the world, though this may be due to differences in screening and kidney biopsy. It is estimated to affect 2.5 per 100 000 adults worldwide. However in Japan it is as high as 1.6%. The differences between countries suggest that IgA nephropathy is likely underdiagnosed, and many cases never come to medical attention.
IgA is a type of antibody that the body has that protects you from infections. It is mostly concentrated in the digestive and respiratory tracts.
Those with IgA nephropathy have an abnormal IgA antibody. This then causes the body to attack it. The end product of this process ends up being deposited into the glomerulus (the filtering unit of the kidney).
More than 90% of all cases of IgA nephropathy appear to happen spontaneously. However there is a genetic link: many relatives of those with IgA nephropathy have abnormalities in the urine.
How will IgA nephropathy affect my kidney function?
The course of IgA nephropathy varies between people. For many people it does not cause end stage kidney disease. In longterm studies, after 20 years 20% will have progressive kidney impairment, and another 25% will have end stage kidney disease.
Risk factors that hasten the course of IgA nephropathy include high blood pressure, obesity and smoking. The good news is that you can control these factors.
Another factor is what the biopsy looks like. To confirm the diagnosis, a sample of kidney is retrieved under local anaesthetic. The pathologist will look under the microscope and grade the tissue (MEST-C grading). Briefly, this looks at:
· The amount and location of deposition in the glomerulus
· The amount of scarring
· How active the IgA nephropathy is
In a sample where there is much scarring, the prognosis becomes less favourable. By contrast if there is minimally active disease without scarring, the prognosis is favourable.
Is there a cure for IgA nephropathy? Are there any dietary restrictions or changes I need to make?
There are a few categories we can fit those with IgA nephropathy in which streamlines our management. These include:
· Those with a “good” prognosis. These are people who have only minor abnormalities in their urine (eg urine protein – a sign of kidney damage – less than 500mg per day), but a normal kidney function and blood pressure
· Those with an “intermediate” prognosis. These are people with a significant amount of protein in their urine (more than 500mg per day), slowly declining kidney function and high blood pressure
· Those with a “poor” prognosis. These are people with a rapid decline in their kidney function.
For all patients, blood pressure should be controlled. First line therapy is usually an ACE inhibitor (these drugs usually end with “-pril”) or ARB (usually ending with “-sartan”). A newer therapy that has come on the Australian market in 2022 are SGLT2 inhibitors (Empagliflozin also called Jardiance, dapagliflozin also called Forxiga). These work by decreasing pressure into the kidneys. So don’t be surprised if your kidney function looks lower when your doctor rechecks your bloods after starting these medications. They protect the kidney function long term. The end goal is to decrease urine protein to less than 1g per day.
Your kidney specialist may prescribe fish oil. These are theorised to work by decreasing inflammation. Besides a fishy taste, its main side effect is flatulence.
In carefully selected patients with progressive disease, immunosuppression may be considered. The evidence of benefit is strongest in those with “poor” prognosis disease. Side effects are considerable. For instance, cyclophosphamide can cause infertility. Prednisolone causes increased weight, skin thinning, osteoporosis (fragile bones), infections, stomach ulcers, swelling, weak muscles, acne and changes to mood. Trials are ongoing to maximise benefit whilst minimising harm. Have a discussion with your specialist if you would be suitable.
You may read about tonsillectomy as a possible cure. The idea is to remove sites where IgA is produced. This practice is strongest in Japan, but is not done in Australia due to weak evidence.
What are the symptoms of IgA nephropathy and when should I see a doctor?
There are a few ways that may signal the possibility of IgA nephropathy. These include:
· Visible blood in the urine – It only takes a few drops of blood to make the urine change colour. Usually the urine is more of a brown colour than bright red. Often the common cold is a trigger for these episodes. The urine colour will usually get better by itself after a few days. 50% of those with IgA nephropathy have these episodes. Even if not visible, there is usually a small amount of blood in the urine if viewed under the microscope.
· Microscopic amounts of blood and protein in the urine – This is usually picked up on routine testing for other reasons, eg a checkup for military service. Up to 40% of cases are picked up this way.
· Nephrotic syndrome – This is a constellation of symptoms include high blood pressure, swelling of the legs and very heavy protein in the urine. This picks up 5% of people with IgA nephropathy
· Acute kidney injury – This is an uncommon way to diagnose IgA nephropathy. This may occur for instance in rapidly progressive IgA nephropathy.
How will IgA nephropathy impact my daily life and activities?
IgA nephropathy is a cause of chronic kidney disease. If it progresses, then changes may need to be made to diet and medications. This is why it is important to control risk factors for progression: stop smoking, control weight, exercise and have a low salt diet. If the kidney function drops to less than 20% (20mL/min/1.73m2) then your doctor may discuss end stage disease planning.
If well controlled, IgA nephropathy may not have too much of an impact on your life, save the occasional episode of blood in the urine.
For a video I presented to colleagues, click here
