Iga Nephropathy: Symptoms, Types, Causes and Treatment

IgA nephropathy, also known as Berger’s disease, is the most common primary glomerulonephritis globally and a leading cause of chronic kidney disease. This complex condition arises from the deposition of immunoglobulin A (IgA) in the kidneys, triggering inflammation and progressive damage to the renal tissue. While some individuals experience mild or even no symptoms, others may develop severe complications over time. In this article, we’ll explore the key symptoms, types, underlying causes, and current as well as emerging treatments for IgA nephropathy, helping you understand this challenging disease from multiple perspectives.

Symptoms of IgA Nephropathy

IgA nephropathy manifests with a broad and sometimes subtle range of symptoms, often making early detection challenging. The clinical picture varies greatly between individuals, from silent urinary findings to dramatic kidney failure. Recognizing these symptoms is crucial for timely diagnosis and management.

Symptom	Frequency/Impact	Associated Features	Source(s)
Hematuria	Common; can be visible/invisible	Often after infections	1 3 4 7
Proteinuria	Frequent	Sometimes mild, sometimes nephrotic	1 4 7
Hypertension	Increases with age/severity	Correlates with kidney dysfunction	1 4 7
GI Symptoms	More common than in controls	Includes diarrhea, constipation	2
Edema	Uncommon but possible	More likely with nephrotic syndrome	1 4
Kidney Failure	Progressive in some	Chronic or acute	1 4 7

Table 1: Key Symptoms

Hematuria: The Signature Symptom

One of the hallmark features of IgA nephropathy is hematuria—blood in the urine. This can be macroscopic (visible to the eye) or microscopic (only detected by tests). Macroscopic hematuria often occurs after respiratory or gastrointestinal infections, particularly in younger patients. In some cases, the urine may appear tea- or cola-colored. Microscopic hematuria, on the other hand, might be persistent but unnoticed without laboratory testing 1 3 4 7.

Proteinuria: A Marker of Disease Activity

Proteinuria—excess protein in the urine—can range from mild to severe. While many patients have only small increases, significant proteinuria (sometimes reaching nephrotic levels) signals a higher risk of disease progression and kidney damage 1 4 7.

Hypertension and Edema

As kidney function declines, patients often develop high blood pressure (hypertension). This is both a symptom and a risk factor for further kidney injury. Edema (swelling), while less common, can occur, especially if protein losses are severe enough to cause a nephrotic syndrome 1 4 7.

Gastrointestinal Symptoms

Recent research shows that gastrointestinal (GI) symptoms—including diarrhea, constipation, and reflux—are more common in IgA nephropathy patients than in the general population. These symptoms often occur even before kidney function is clearly reduced, particularly in females 2.

Renal Function Decline

IgA nephropathy can be silent for years but may eventually lead to chronic kidney disease or even acute or chronic renal failure. The risk increases with age, high blood pressure, and persistent proteinuria 1 4 7.

Types of IgA Nephropathy

IgA nephropathy is not a one-size-fits-all disease. It presents in several forms, each with unique clinical implications. Understanding these types helps tailor management and predict outcomes.

Type	Definition/Presentation	Key Features	Source(s)
Primary IgAN	Occurs without other diseases	Most common; immune-complex mediated	4 5 7 8
Secondary IgAN	Linked to other conditions	Associated with liver, GI, others	6
Rapidly Progressive	Sudden severe kidney decline	Rare, aggressive	7
Overlapping Syndromes	Mixed features (e.g., thin-basement-membrane nephropathy)	Diagnostic challenge	13

Table 2: Types of IgA Nephropathy

Primary IgA Nephropathy

This is the classic form, developing in the absence of other systemic diseases. It is characterized by the deposition of IgA immune complexes in the glomeruli and is diagnosed via kidney biopsy 4 5 7 8.

Secondary IgA Nephropathy

In some patients, IgA nephropathy occurs alongside other diseases, such as:

• Chronic liver disease (especially cirrhosis)
• Inflammatory bowel diseases
• Certain infections or malignancies

These cases are termed secondary IgA nephropathy and may have different triggers and management considerations 6.

Rapidly Progressive IgA Nephropathy

A minority of patients develop a rapidly progressive form, marked by a sudden and severe loss of kidney function. This variant is associated with more aggressive inflammation and often a worse prognosis 7.

Overlapping and Variant Syndromes

Some individuals exhibit features of both IgA nephropathy and other glomerular disorders, such as thin-basement-membrane nephropathy. These overlapping syndromes may complicate diagnosis and require specialized management 13.

Causes of IgA Nephropathy

The origins of IgA nephropathy are multifaceted, involving a combination of genetic, immunological, and environmental factors. Although our understanding continues to evolve, several key mechanisms have been identified.

Cause	Mechanism/Factor	Notable Points	Source(s)
Genetic	Susceptibility loci, family risks	Higher prevalence in some populations	9 10 11 12
Immune Abnormality	Aberrant IgA1 glycosylation	Central to pathogenesis	4 7 9 11 12
Autoantibodies	Against galactose-deficient IgA1	Promote immune-complex formation	4 7 9 12
Environmental	Infections, mucosal triggers	May stimulate abnormal IgA production	12
Complement Activation	Inflammatory mediator	Linked to disease activity/progression	16

Table 3: Causes of IgA Nephropathy

Genetic Predisposition

Family studies and genome-wide association analyses have uncovered numerous genetic loci associated with increased risk of IgA nephropathy. These loci often involve genes related to immune regulation and IgA production. Notably, prevalence is higher in East Asian and some European populations, correlating with genetic risk profiles 9 10 11 12.

Aberrant IgA1 and Autoimmune Processes

Central to the disease is the production of aberrantly glycosylated IgA1—specifically, IgA1 molecules with galactose-deficient O-glycans. These abnormal IgA1 molecules are prone to form immune complexes, especially when targeted by anti-glycan autoantibodies (IgG or IgA). The resulting complexes deposit in the glomerular mesangium, leading to local inflammation and damage 4 7 9 11 12.

Mucosal Immune Triggers and Environmental Factors

Recurrent infections, particularly of the upper respiratory and gastrointestinal tracts, are thought to stimulate mucosal immune responses, favoring the production of nephritogenic IgA1. Tonsillitis and other mucosal challenges can act as disease triggers in genetically susceptible individuals 12.

Complement System Activation

The complement cascade, especially the alternative and lectin pathways, is strongly implicated in the progression of IgA nephropathy. Complement proteins are often found alongside IgA deposits in the kidney and are associated with worse outcomes, highlighting a potential therapeutic target 16.

Treatment of IgA Nephropathy

While there is currently no cure, treatment for IgA nephropathy focuses on slowing disease progression, managing symptoms, and targeting underlying mechanisms when possible. Recent advances are paving the way for more specific therapies.

Treatment	Approach/Goal	Key Details/Considerations	Source(s)
Supportive Care	Blood pressure & proteinuria control	First-line for most patients	4 7 13 17
Corticosteroids	Reduce inflammation	For persistent proteinuria; risks	7 13 14 17
Immunosuppressives	Target immune system	Limited use; evidence mixed	13 14 17
New Therapies	Novel targets (e.g. complement, B cells)	Under investigation, promising	7 15 16 17

Table 4: Treatment Approaches

Supportive Care: The Foundation

For the majority of patients, optimized supportive care is the cornerstone of management. This includes:

• Strict blood pressure control (often with ACE inhibitors or ARBs)
• Reducing proteinuria
• Lifestyle modifications (diet, exercise, quitting smoking)
• Controlling other cardiovascular risk factors

Supportive care reduces the risk of progression to kidney failure and is recommended for all patients 4 7 13 17.

Corticosteroids and Immunosuppressive Therapy

Corticosteroids (such as prednisone) may be considered for patients with persistent proteinuria (>1 g/day) despite supportive care. However, their use is controversial due to potential side effects—especially in those with declining kidney function. High-dose, short-term therapy appears more beneficial than low-dose, long-term regimens. Other immunosuppressive agents (like mycophenolate mofetil) have limited roles, except possibly in specific populations 7 13 14 17.

Emerging and Targeted Therapies

Recent research and clinical trials are exploring new approaches, including:

• SGLT2 inhibitors for renal protection
• Complement inhibitors (e.g., eculizumab)
• B-cell targeted therapies (e.g., anti-APRIL antibodies)
• Targeted-release budesonide

These therapies aim to address the underlying immune abnormalities or block the inflammatory cascades driving the disease. Early results are promising, but more evidence is needed before they become routine care 7 15 16 17.

Conclusion

IgA nephropathy is a complex, lifelong kidney disease with highly variable presentation and progression. Understanding its symptoms, types, causes, and treatments is crucial for optimizing patient care and outcomes. Here’s a summary of the main points:

• Symptoms range from invisible hematuria and mild proteinuria to severe hypertension and kidney failure. GI symptoms are also more common than previously appreciated.
• Types include primary, secondary, rapidly progressive, and overlapping syndromes, each requiring tailored management.
• Causes involve a mix of genetic susceptibility, abnormal IgA1 production, autoimmune processes, environmental triggers, and complement activation.
• Treatment focuses on supportive care as first-line, with corticosteroids and emerging targeted therapies considered for high-risk or progressive cases.

Ongoing research continues to unravel the complexities of IgA nephropathy and promises more effective, individualized therapies in the near future.