IgA nephropathy: the complete guide for patients

IgA nephropathy is the most common form of glomerulonephritis I see in my clinic, and the condition has changed substantially in how it is treated over the last few years. New trials have produced new options. I have written this guide to give patients the clearest possible picture of what the condition is, what to expect, and how my approach to managing it has evolved.

IgA nephropathy is the most common form of glomerulonephritis in Ireland and worldwide. Despite being common, it is poorly understood by most patients who are diagnosed with it. It is also a condition that has changed substantially in the last decade, with new treatments coming through clinical trials and the standard of care evolving rapidly. This guide walks through what IgA nephropathy is, how it presents, how it is diagnosed, how it is treated, and what to expect over the long term.

IgA nephropathy is caused by deposition of an antibody called immunoglobulin A in the filtering units of the kidneys. Immunoglobulin A is a normal antibody, produced throughout the body and particularly in the mucous membranes of the gut and respiratory tract. In people with IgA nephropathy, an abnormal form of IgA is produced. This abnormal IgA is recognised by the immune system as foreign, antibodies are made against it, and the resulting immune complexes deposit in the glomeruli (the filtering units) of the kidneys. The deposits trigger inflammation and gradually cause scarring of the filters.

The condition was first described in 1968 by a French nephrologist, Jean Berger, which is why it is sometimes called Berger’s disease. Since then, it has become clear that it is the most common form of glomerulonephritis worldwide, with an incidence of around 1 to 5 per 100,000 people per year. It is more common in people of East Asian heritage, although it occurs in all populations. It affects more men than women, in a ratio of around two to one. The typical age of presentation is in the twenties and thirties, but it can present at any age from childhood through old age.

IgA nephropathy presents in several recognisable patterns. The most distinctive is recurrent visible haematuria that appears during or shortly after an upper respiratory tract infection or, less commonly, a gastrointestinal infection. The blood typically appears in the urine within a day or two of the infection starting and clears within days. The pattern often recurs with subsequent infections. Patients sometimes describe many years of this pattern before a diagnosis is made.

The second pattern is persistent non-visible haematuria, often picked up incidentally on a urine dipstick performed for some other reason. The blood is always present in small quantities, although it is not visible to the eye. This pattern accounts for many cases that come to light only when a urine test is done as part of routine assessment.

The third pattern is proteinuria, often combined with non-visible haematuria. Protein leakage on its own can be the first sign, particularly when significant. The presence of both protein and blood in the urine is a strong signal of glomerular disease, and IgA nephropathy is one of the most common causes.

A smaller proportion of patients present with a more acute picture: rapidly developing hypertension, oedema, and reduced kidney function. This is the picture of acute nephritic syndrome and warrants urgent specialist input.

The diagnosis of IgA nephropathy is made by kidney biopsy. There is no blood test that confirms it. The biopsy shows the characteristic deposition of IgA in the mesangium (the supporting matrix of the glomerulus). Routine blood tests can support the suspicion but cannot make the diagnosis. Serum IgA levels, often referred to in older textbooks, are normal in many patients with IgA nephropathy and elevated in many people without it, so they are not a reliable test.

The biopsy also provides important prognostic information. The Oxford classification is a widely used grading system that assesses the biopsy on several features: mesangial hypercellularity, endocapillary proliferation, segmental glomerulosclerosis, interstitial fibrosis and tubular atrophy, and the presence of crescents. Each feature carries prognostic weight, and the combination informs treatment decisions and the conversation about long-term outlook.

The outlook for IgA nephropathy varies enormously between individuals. Some patients have a mild form that never progresses and requires only monitoring. Others have a more aggressive form that leads to significant kidney function loss over years to decades. Around a quarter of patients eventually require dialysis or transplantation, although this proportion has been falling with better treatment. The key predictors of progression are persistent significant proteinuria, hypertension, reduced kidney function at presentation, and certain features on the biopsy.

Treatment of IgA nephropathy has changed substantially over the last few years. The foundation for everyone remains excellent blood pressure control, usually with an ACE inhibitor or angiotensin receptor blocker, which also reduces protein leakage from the filters. The target blood pressure is below 130/80 in most patients. Lifestyle measures including a moderate-sodium diet, weight management, regular exercise, and avoidance of NSAIDs are important.

SGLT2 inhibitors are now recommended for most patients with IgA nephropathy who have significant proteinuria, regardless of whether they have diabetes. The trial evidence (including the DAPA-CKD trial) shows that SGLT2 inhibitors reduce proteinuria and slow the rate of kidney function decline in proteinuric kidney disease.

For patients with persistent significant proteinuria despite optimal supportive therapy, or with rapidly progressive disease, immunosuppression may be considered. The classical approach has been corticosteroids, typically as a six-month course. More recent evidence (the TESTING trial) supports the use of corticosteroids in selected patients with persistent proteinuria, with attention to the side effects.

Newer treatments are emerging. Targeted-release budesonide (Nefecon) delivers steroid action directly to the gut, where the abnormal IgA is produced. This approach has shown benefit in trials and is now licensed for IgA nephropathy in several countries. Sparsentan (a dual endothelin and angiotensin receptor antagonist) has also shown benefit. Other agents including complement inhibitors and B-cell targeted therapies are being studied. The treatment toolkit for IgA nephropathy in the next few years is likely to look very different from what it was a decade ago.

Monitoring is the foundation of long-term care. Regular checks of kidney function, urine protein, blood pressure, and overall cardiovascular risk allow treatment to be adjusted as needed. Specialist follow-up is typically every three to twelve months depending on the stability of the condition.

Lifestyle questions come up frequently. Diet does not change the course of IgA nephropathy in any specific way, although a generally healthy diet with attention to salt and protein is sensible. Exercise is encouraged and is beneficial. Pregnancy is generally safe for women with IgA nephropathy and stable kidney function, but it requires planning and specialist input. Vaccinations are encouraged, including flu, pneumococcal, and COVID-19. Smoking should be stopped completely.

Family questions are also common. IgA nephropathy is not directly inherited in most cases, although there is a small familial tendency. First-degree relatives have a slightly increased risk, but routine family screening is not normally recommended unless there is a strong family history.

If you have been diagnosed with IgA nephropathy, the most important things to know are that the diagnosis is not a verdict, the rate of progression varies hugely between individuals, and consistent treatment of blood pressure and proteinuria substantially improves the long-term outlook. Specialist follow-up matters because treatment options for this condition are changing rapidly. The patient who first presents this year may have substantially more treatment options over the next decade than would have been imagined a decade ago.

I see private patients at Blackrock Clinic, The Beacon Hospital, Bon Secours Dublin, the Hermitage Medical Centre, and St Vincent’s Private Hospital. If you would like a consultation about your kidney health, you or your GP can contact my secretary through drrorymcquillan.ie. Most patients are seen within two to three weeks of referral.