IgA nephropathy (IgAN) is a chronic kidney disease caused by the buildup of immune deposits within the kidneys’ filtering units, known as glomeruli. These deposits are primarily composed of Immunoglobulin A (IgA), an antibody protein designed to fight infection. The condition is the most common form of primary glomerulonephritis worldwide, affecting the kidney’s ability to clear waste and excess fluid from the blood. While the disease course is highly variable, early diagnosis and consistent treatment can significantly slow the progression of kidney damage.
Understanding IgA Nephropathy
IgA nephropathy (Berger’s Disease) begins with an abnormality in the IgA molecule itself. The root cause involves a structural defect in the IgA1 subtype, specifically a deficiency of galactose sugars in its hinge region. This aberrant molecule is referred to as galactose-deficient IgA1 (Gd-IgA1).
The body’s immune system recognizes this structurally altered Gd-IgA1 as foreign and produces autoantibodies (IgG) to target it. These antibodies bind to the Gd-IgA1, forming large immune complexes that circulate in the bloodstream. These complexes then become trapped in the mesangium, the central area of the kidney’s glomeruli, due to their size and composition.
Once deposited, the immune complexes trigger an inflammatory cascade that causes the mesangial cells to proliferate and secrete factors that lead to scarring. This inflammation and subsequent scarring, known as glomerulosclerosis, gradually impairs the glomeruli’s ability to filter blood effectively. The connection between IgAN and mucosal immunity is often noted, as the disease frequently flares following respiratory or gastrointestinal infections, suggesting a link to the body’s first line of defense.
Recognizing Signs and Confirmation
IgA nephropathy can often be described as a silent disease, as many individuals experience no noticeable symptoms in the early stages. The most common sign is the presence of blood in the urine (hematuria), which can be either microscopic or visible. This visible blood, sometimes described as cola-colored or dark, often appears within a day or two of an upper respiratory or gastrointestinal infection, a presentation known as synpharyngitic glomerulonephritis.
Another finding is proteinuria, the leakage of protein into the urine due to damage to the glomerular filter. High levels of protein can cause the urine to appear foamy, and the protein loss can lead to fluid accumulation and swelling (edema), particularly in the feet, ankles, and around the eyes. Sustained high blood pressure is also a frequent complication and sign of worsening kidney function.
The initial workup involves urine and blood tests to check for hematuria, proteinuria, and an assessment of kidney function. Blood tests measure waste products like creatinine to estimate the glomerular filtration rate (GFR), which indicates how well the kidneys are filtering. The definitive diagnosis requires a kidney biopsy, which uses a needle to obtain a small tissue sample examined under a microscope to confirm IgA deposits in the mesangium.
Management Strategies
The primary goal of managing IgA nephropathy is to slow the progression of kidney damage and preserve the existing kidney function. The cornerstone of treatment is supportive care, focusing on aggressively controlling blood pressure and reducing proteinuria. Medications known as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are preferred for this purpose.
These agents not only lower blood pressure but also exert a protective effect on the kidneys by reducing the pressure within the glomeruli, which significantly decreases protein leakage. Optimal blood pressure control is targeted below 130/80 mmHg. Achieving a reduction in proteinuria is a major therapeutic objective, as the amount of protein in the urine is strongly linked to the risk of progression.
For patients who continue to have high levels of proteinuria (typically one gram per day or more) despite optimized supportive care, immunosuppressive therapy may be considered. This often involves a course of corticosteroids (steroids), which aim to dampen the underlying immune-driven inflammation. Newer therapies, including sodium-glucose cotransporter 2 (SGLT2) inhibitors and targeted drugs like budesonide and sparsentan, have also emerged as options to further reduce proteinuria and slow disease advancement in high-risk patients.
Lifestyle adjustments are important. These modifications include adopting a low-sodium diet to help control blood pressure and swelling, and potentially moderating protein intake. Patients are generally advised to avoid non-steroidal anti-inflammatory drugs (NSAIDs) because these common pain relievers can potentially harm the kidneys.
Disease Progression and Long-Term Outlook
The trajectory of IgA nephropathy is notably varied, ranging from a mild condition that remains stable for decades to a more aggressive form that leads to rapid kidney decline. For many patients, the disease may never progress to severe kidney failure, but a significant portion (20% to 40%) will progress to End-Stage Renal Disease (ESRD) within 10 to 20 years of diagnosis. ESRD requires life-sustaining treatments such as long-term dialysis or a kidney transplant.
Several factors are recognized as indicators of a less favorable prognosis. These include high levels of persistent proteinuria, elevated blood pressure that is difficult to control, and a reduced GFR at the time of diagnosis. Histological findings from the kidney biopsy, such as the presence of extensive scarring or crescent formation in the glomeruli, also help predict the risk of future decline.
For those who do progress to ESRD and receive a kidney transplant, there is a risk of IgA nephropathy recurring in the transplanted kidney. Despite this possibility, the prognosis for patients with IgAN who receive a transplant is generally positive. Regular monitoring of blood pressure, proteinuria, and GFR is therefore a lifelong requirement to detect early signs of worsening function and adjust the treatment strategy promptly.