IgA nephropathy (IgAN), also known as Berger’s disease, is an autoimmune condition where immunoglobulin A antibodies build up in the kidney’s filters, leading to inflammation and potential kidney failure.
What Causes IgA Nephropathy and Who Is at Risk?
IgAN occurs when the immune system produces an abnormal version of the IgA antibody, specifically galactose-deficient IgA1 (Gd-IgA1). The body recognizes this as a foreign substance and creates antibodies that bind to it. These complexes then lodge in the glomeruli—the tiny blood vessels that filter waste from the blood—triggering inflammation.
Medical professionals categorize the disease into three distinct types:
- Primary IgAN: The most common form, where the disease originates in the kidneys without another underlying cause.
- IgA-Associated Nephropathy: This includes systemic conditions like IgA vasculitis (formerly Henoch-Schönlein purpura), where IgA deposits affect the kidneys, joints, and gastrointestinal tract.
Identifying Symptoms and Diagnostic Procedures
Symptoms of IgAN often develop slowly over several years. The hallmark sign is hematuria, or blood in the urine, which may appear red, brown, or “cola-colored.” This happens because damaged kidney vessels leak blood into the urinary tract.
Other clinical signs include:
- Foamy urine: An indication of proteinuria (excess protein leaking into the urine).
- Edema: Swelling in the face, legs, ankles, or abdomen.
- Hypertension: High blood pressure caused by the kidneys’ inability to regulate fluids.
- General malaise: Persistent tiredness and weakness.
Diagnosis begins with a physical exam and blood pressure screening. A nephrologist will use urinalysis to detect blood and protein, and blood tests to measure creatinine levels and the estimated glomerular filtration rate (eGFR). However, a kidney biopsy is the only way to confirm the diagnosis. During this procedure, a small tissue sample is examined via immunofluorescence to identify specific IgA deposits in the kidney tissue.
Medical Treatment Options and New Therapies
There is currently no cure for IgAN, but medications aim to preserve kidney function. Treatment plans are tailored to the severity of kidney damage and the presence of other health conditions.
Blood Pressure and Protein Management
Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are typically the first line of defense. These drugs lower blood pressure and reduce the amount of protein leaked into the urine. Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, originally developed for diabetes, are also used to slow disease progression.
Targeted and Immune-Modulating Drugs
Recent advancements have introduced more targeted therapies to reduce inflammation:
- Endothelin Receptor Antagonists (ERAs): Drugs like sparsentan (Filspari) and atrasentan (Vanrafia) widen kidney blood vessels to preserve function.
- Corticosteroids: Steroids can calm the immune system, though long-term use is avoided due to risks of bone loss and high blood sugar. The targeted-release steroid budesonide (Tarpeyo) is designed to have fewer systemic side effects.
- Complement Factor B Inhibitors: Iptacopan (Fabhalta) targets the immune system to reduce proteinuria.
- Monoclonal Antibodies: Sibeprenlimab-szsl (Voyxact) blocks the proliferation-inducing ligand (APRIL) protein, which drives the production of IgA antibodies.
Long-Term Prognosis and Potential Complications
IgAN is a progressive disease with highly variable outcomes. While some patients remain stable for decades, research indicates that high levels of protein in the urine significantly increase the risk of kidney failure. Up to half of patients may develop kidney failure within 10 years of diagnosis.
Complications often extend beyond the kidneys:
| Complication | Cause/Mechanism |
|---|---|
| Chronic Kidney Disease (CKD) | Long-term inflammation and scarring of the glomeruli. |
| Nephrotic Syndrome | Severe filter damage leading to high cholesterol and systemic swelling. |
| Cardiovascular Disease | Combination of hypertension and high cholesterol increasing stroke and heart attack risk. |
| End-Stage Renal Disease | Total loss of kidney function, requiring dialysis or transplant. |
For those facing kidney failure, a transplant is an option. However, the disease can recur in the new organ; one study found that nearly 1 in 4 transplant recipients experienced a recurrence of IgAN within 15 years.
Lifestyle Adjustments to Protect Kidney Function
Dietary and lifestyle changes are critical to slowing the progression of IgAN and managing blood pressure.
Dietary Restrictions:
- Sodium: Limit intake to 2,000 mg (about one teaspoon) per day to prevent fluid buildup and high blood pressure.
- Protein: Reduce overall protein intake to lower the workload on damaged kidneys.
- Alcohol: Limit or avoid alcohol, as it can interfere with blood pressure medications.
Risk Mitigation:
Smoking can accelerate kidney damage and increase the likelihood of failure.
Support services are available through the IgA Nephropathy Foundation and the National Kidney Foundation, which provide resources for clinical trials and patient advocacy.