What is IgA nephropathy?

IgA nephropathy is the most common primary kidney disease in the world. Somewhere between 1 and 3 people per 10,000 are diagnosed each year, and among those who develop kidney failure, it accounts for a significant share of cases. Even so, many patients leave their first nephrology appointment with only a partial picture of what they've been told.

This post is an attempt to fill that gap. It's written for people who have just received a diagnosis, for family members trying to understand what's happening, and for anyone who wants to know more without wading through clinical literature.

What the kidneys do

Your kidneys are two fist-sized organs sitting on either side of your spine, just below your rib cage. Every day, they filter roughly 200 litres of blood, keeping what you need and excreting the rest as urine. They also regulate blood pressure, produce a hormone that triggers red blood cell production, and manage the balance of salts and minerals in your blood.

The filtering happens in small units called glomeruli, roughly one million per kidney. Each glomerulus is a tiny tangle of capillaries wrapped in a membrane that acts as a sieve. Protein and blood cells are too large to pass through the sieve and normally stay in the bloodstream. When the sieve is damaged, they leak into the urine.

What goes wrong in IgA nephropathy

IgA stands for immunoglobulin A, a type of antibody your immune system produces mainly to protect mucous membranes in the gut and respiratory tract. In people with IgA nephropathy, some of this IgA has a structural defect: a particular sugar molecule that should be attached to the antibody is missing or incomplete.

The immune system treats this defective IgA as a target. It produces other antibodies against it, and these antibody complexes circulate in the blood until they become trapped in the glomeruli. The resulting inflammation is what we call IgA nephropathy. Over time, repeated rounds of inflammation scar the glomeruli, reducing the kidneys' filtering capacity.

Why some people get worse faster than others

The disease follows very different courses in different people. Some patients have mild proteinuria (protein in the urine) for decades with stable kidney function. Others progress to chronic kidney disease within ten to fifteen years. A smaller group reaches kidney failure relatively quickly.

The factors that predict a faster decline include:

• Higher proteinuria: sustained protein loss above 1 gram per day is an important warning sign
• High blood pressure: accelerates scarring in the glomeruli
• Kidney function at diagnosis: a lower starting GFR (glomerular filtration rate) tends to mean a worse trajectory
• Histology: what the kidney biopsy shows about the degree of existing scarring and inflammation

This is why the biopsy matters. It confirms the diagnosis and gives your nephrologist information that blood and urine tests alone cannot.

How it's diagnosed

The definitive diagnosis is a kidney biopsy. A needle is inserted under imaging guidance to take a small sample of tissue from one kidney. The sample is examined under a microscope, and the presence of IgA deposits in the mesangium (the matrix of the glomerulus) confirms the diagnosis.

Blood tests and urinalysis are done beforehand and will typically show elevated IgA levels in about half of patients, proteinuria, and sometimes blood in the urine (hematuria). These findings raise suspicion, but only the biopsy confirms it.

Treatment

Until recently, treatment options were limited. The main approaches were:

• Blood pressure control, primarily with ACE inhibitors or ARBs, which also reduce protein leak from the kidney
• Fish oil (omega-3 fatty acids), supported by some trial data but not universally recommended
• Corticosteroids in patients at higher risk of progression, though their benefit has been contested

This has changed in the past few years. Sparsentan, a dual-acting drug that blocks both angiotensin and endothelin receptors, has been approved for IgA nephropathy after trial data showed meaningful reduction in proteinuria. SGLT2 inhibitors, a class of drugs developed for type 2 diabetes, have also shown a protective effect on kidney function across several kidney diseases, including IgA nephropathy. And a new class of drugs targeting the complement pathway (part of the immune system implicated in kidney inflammation) is in clinical trials.

It's a field moving faster than it has in a long time. If you're seeing a nephrologist, ask specifically about newer agents and whether you might be eligible for any ongoing trials.

What to ask your doctor

Here are questions worth raising at your next appointment:

1. What does my biopsy report say about the Oxford classification score? (This is a standardized way of describing the biopsy findings.)
2. What is my current GFR, and how has it trended over the past year?
3. What is my urine protein-to-creatinine ratio?
4. Are you recommending an ACE inhibitor or ARB, and what is the target blood pressure?
5. Am I a candidate for any newer treatments, such as sparsentan or an SGLT2 inhibitor?
6. Are there any trials at this institution or nearby that might be appropriate for me?

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This post is adapted from material in my book, IgA Nephropathy: A Patient and Family Guide, which covers the disease in more depth, including later-stage management, transplantation, and living with the condition.