IgA Nephropathy

IgA nephropathy is a kidney disorder that occurs when IgA—a protein antibody that helps the body fight infections—gets deposited in the kidneys, in an area called the mesangium. After many years of IgA deposits, the kidneys leak blood and protein into the urine, which can mean serious kidney damage.

The disease, a type of kidney disorder called a glomerulonephritis, is the most frequent type of glomerulonephritis ^[1] and is more common in young men of Southern Europe and the Pacific Rim,^[2]. It is closely related to the disease Henoch-Schonlein purpura, in which the IgA is deposited not only in the kidney but also in the skin and blood vessels.

Approximately 25% of adults with IgA nephropathy develop total kidney failure,^[2] while only 5%–10% of children do so. Symptoms of kidney failure include swelling in the hands and feet, nausea, fatigue, headaches, and sleep problems. People with kidney failure need dialysis or a kidney transplant.

Other Names

• Immunoglobulin A nephropathy
• IGAN
• Berger disease
• Synpharyngitic glomerulonephritis: This term is used to distinguish IgA nephropathy from the disease poststreptococcal glomerulonephritis, in which the kidney problems begin several weeks after (post-) a sore throat (often caused by the germ Streptococcus). In IgA nephropathy, the disease occurs shortly after or with (syn-) the sore throat (pharyngitis).

Types

Some researchers suspect that the IgA deposits may be a common response to a wide range of triggers, and that as the disease is better understood it will turn out to have numerous types.^[2] At present, however, all IgA nephropathy is described as one disease.

Signs and Symptoms

In the early stages, IgA nephropathy has no symptoms, so it can go unnoticed for years, even decades. In about 30%&ndash40% of cases, the first sign is noticeable blood in the urine (macroscopic hematuria) that intermittently appears during or just after a cold, sore throat, or other infection.^[2] At times, blood in the urine is so slight (microscopic hematuria) that it can only be detected by urine tests. Blood in the urine may cause it to look pink or the color of tea or cola.

Less than 5% of the time, the disease shows up as sudden, or acute, kidney failure. Another rare way for it to appear is as sudden, extremely high blood pressure, or malignant hypertension.^[2]

Causes

Scientists do not know what causes IgA deposits to form in the kidneys. IgA nephropathy may run in families or be related to respiratory infections. No consistent trigger for the disease has been found. Genetic factors are thought to be partly responsible, though, especially as they relate to the body's inherent tendency to react to the deposits with inflammation.^[2]

Diagnosis

A urine test, or urinalysis, usually provides the first clues. In a urinalysis, the doctor or nurse dips a chemical-coated strip into the urine sample. The strip changes color when blood or protein is present in the urine (neither is normally there). If the test strip is positive, the urine will then be examined with a microscope to look for red blood cells. The red blood cells may be clumped together to form little tubes. These tubes are called casts because they are formed or molded inside the kidneys' tiny draining structures. If casts are found, it usually means the kidney filters are damaged.

Blood tests measure the waste products in the blood that the kidneys usually get rid of. Two examples are creatinine and blood urea nitrogen (BUN). If the BUN and creatinine levels are high, it means the kidneys are not working well. If the creatinine level is high at the time of diagnosis, the patient is more likely to develop kidney failure.

If tests suggest there is kidney damage, the doctor will probably recommend a kidney biopsy. In this procedure, a needle is used to retrieve a small piece of kidney tissue for examination with different microscopes. Only a biopsy can show the IgA deposits in the kidney filters and allow the diagnosis to be made. The biopsy can also tell how much kidney damage has already occurred and help the doctor determine the best treatment. Once a diagnosis of IgA nephropathy is established, patients should have regular blood tests to monitor how their kidneys are doing.

Treatment

Treatment of IgA nephropathy mainly focuses on slowing the disease down and preventing complications. Not all patients require treatment—some just need careful monitoring over time—but kidney specialists generally agree that patients with both blood and protein (usually exceeding 1 g/day) in their urine should be treated.

Medications

There are two distinct approaches to the treatment of IgA nephropathy. One approach involves suppressing the immune system, while the other does not.

Non-immunosuppressive

Because the kidney is damaged by high blood pressure, and because kidney damage can itself lead to high blood pressure, this approach focuses on controlling blood pressure with medications. The medications most often used are angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), since these drugs not only lower blood pressure but also tend to protect the kidney and reduce the amount of protein it sheds. However, often a patient will need to take several different blood pressure medications, each of which works a different way, to get blood pressure under control. Although ACE inhibitors and ARBs (and perhaps a new type of drug called a renin inhibitor) are the first blood pressure medications that should be given, the most important factor is getting the blood pressure down to the recommended level with whatever medications are most effective. The blood pressure goal is less than 130/80 mmHg. Some research suggests that people with greater than 1 g/day (1000 mg/day) of proteinuria should have their blood pressure lowered to under 125/75 mmHg. In addition to getting their blood pressure down to recommended targets, all patients should receive drugs called statins to lower their cholesterol.

Fish oil supplements high in omega-3 fatty acids might slow the progression of IgA nephropathy by reducing inflammation, though analyses of multiples studies have not found an effect.^[3] If there is a benefit it is likely to be subtle.

Immunosuppressive

In addition to receiving the general approach, there are some patients who benefit from stronger treatments. Medications that suppress the immune system are often prescribed for patients with a higher likelihood of progressive renal damage. Signs that a patient falls into this category include: (1) a high serum creatinine upon first diagnosis, (2) high blood pressure, and (3) protein in the urine greater than 500mg/day. The small specimen of kidney retrieved during the biopsy may also show clues when examined under the microscope that a patient is more likely to suffer kidney damage as time goes on.

In such instances medicines such as prednisone may help treat IgA nephropathy. Prednisone belongs to a class of medicines called corticosteroids, which can have harmful side effects. One of the newer immunosuppressive agents called mycophenolate mofetil (MMF) is also being tested in treating IgA nephropathy.

Other treatments

Because of the link between throat infections and IgA nephropathy, tonsillectomy has been advocated as a treatment, but the evidence in favor of its usefulness is weak.^[3]

Chances of Developing IgA Nephropathy

Risk factors

IgA nephropathy can occur at any age, including in childhood. More men are affected than women, often men in their teens and twenties.^[2] Although it is found all over the world, IgA nephropathy is more common among Caucasians and Asians, and is particularly common in Pacific Rim and Southern European residents.^[2] It is one of the most common diseases of the kidney other than those caused by diabetes or high blood pressure.

Diseases Associated with IgA Nephropathy

Idiopathic (majority)

• Renal-limited or as a component of Henoch Schonlein purpura

In association with systemic diseases or drugs

Celiac Disease

Patients with IgA Nephropathy carry an increased risk to contract celiac disease.^[4] This can be explained by the higher level of common antibodies in CD and in IgAN suggesting a genetic predisposition of the mucosal defect in IgAN that might allow gluten-derived peptides to enter the submucosa.^[5] This association between intestinal inflammation and increased intestinal permeability may be involved in the pathogenesis of both conditions.

• Liver- Chronic liver disease with biliary involvement
• Gastrointestinal- Crohn's disease, adenocarcinoma
• Respiratory- idiopathic interstitial pneumonitis, obstructive bronchiolitis, adenocarcinoma
• Skin- Dermatitis herpetiformis, mycosis fungoides, leprosy
• Eyes- Episcleritis, anterior uveitis
• Miscellaneous- Ankylosing spondylitis, relapsing polychondritis, Sjogren's syndrome, schistosomiasis

Clincal Trials

For a list of American government-sponsored clinical trials studying IgA nephropathy, click here.

Drug Therapy for the Treatment of IgA Nephropathy is a trial orchestrated by the Mayo Clinic.

Research

In recent years, researchers have learned much about kidney disease. In the United States, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsors several programs aimed at understanding kidney failure and finding treatments to stop its progression.

The NIDDK's Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) supports basic research into normal kidney function and the diseases that impair normal function at the cellular and molecular levels, including diabetes, high blood pressure, glomerulonephritis, and other diseases marked by protein in the urine.

Researchers sponsored by DKUHD are studying families in which IgA nephropathy is prevalent in order to understand genetic factors that may influence the disease. Other researchers are working to understand how the polyunsaturated fatty acids found in fish oils may work to reduce inflammation in diseases like IgA nephropathy and rheumatoid arthritis. Clinical trials are under way to test the effectiveness of the drug MMF in reducing protein in the urine and slowing the progression of kidney disease in people with IgA nephropathy.

History

Jean Berger and Hinglais first described the disease in 1968, although the related disease Henoch-Schonlein purpura had been described over a century before.^[6]

References

1. ↑ Nair R, Walker PD. Is IgA nephropathy the commonest primary glomerulopathy among young adults in the USA? Kidney Int. 2006 Apr;69(8):1455-8. Abstract | Full Text | PDF
2. ↑ ^{2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7} Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol. 2005 Jul;16(7):2088-97. Epub 2005 Jun 1. Abstract | Full Text
3. ↑ ^{3.0 3.1} Ballardie FW. IgA nephropathy treatment 25 years on: can we halt progression? The evidence base. Nephrol Dial Transplant. 2004 May;19(5):1041-6. Citation | Full Text
4. ↑ Collin P, et al. Celiac disease and HLA DQ in patients with IgA nephropathy.Am J Gastroenterol. 2002 Oct;97(10):2572-6. Abstract | Full Text | PDF
5. ↑ Almroth G, et at. Increased prevalence of anti-gliadin IgA-antibodies with aberrant duodenal histopathological findings in patients with IgA-nephropathy and related disorders. Ups J Med Sci. 2006;111(3):339-52.[1] | PDF
6. ↑ Berger J, Hinglais N. Intercapillary deposits of IgA-IgG. J Urol Nephrol (Paris). 1968 Sep;74(9):694-5. French. Citation

Other Resources

Nephropathy Support Network