Background

• Primary Immunoglobulin A (IgA) Nephropathy, also known as Berger’s disease, is a chronic autoimmune disease that affects the kidneys. It is characterized by the deposition of immunoglobulin A (IgA) antibody complexes in the glomeruli. This deposition causes inflammation, which can eventually lead to scarring and damage to the glomeruli. Primary IgA Nephropathy is the most common form of glomerulonephritis worldwide, accounting for approximately 25-30% of cases. It typically presents in young adults, with a male predominance.

Epidemiology

• Prevalence: The prevalence varies across different populations and ethnicities. It is more commonly observed in Asian countries, including China, Japan, and Korea, where it is a leading cause of chronic kidney disease. 
• Age and Gender Distribution: Primary IgA Nephropathy can affect individuals of all age groups, from children to older adults.  
• Ethnic Variations: The prevalence of Primary IgA Nephropathy varies among different ethnic groups. It is more prevalent in Asian populations, including Chinese, Japanese, and Korean, as mentioned earlier. 
• Familial Clustering: There is evidence of familial clustering in Primary IgA Nephropathy, suggesting a genetic predisposition to the disease. 
• Geographical Differences: The incidence and prevalence of Primary IgA Nephropathy vary across different geographical regions. It is more common in regions with higher rates of streptococcal infections, suggesting a possible association between infections and the development of IgA Nephropathy.  
• Risk Factors: Certain risk factors may also contribute to the development or progression of Primary IgA Nephropathy. These include family history of the disease, preceding upper respiratory tract infections or gastrointestinal infections, and specific genetic polymorphisms associated with immune dysregulation. 

Anatomy

Pathophysiology

• IgA Deposition: In Primary IgA Nephropathy, there is an abnormal accumulation of IgA immune complexes in the glomeruli of the kidneys. 
• Abnormal IgA Production: The underlying defect in Primary IgA Nephropathy lies in the production of abnormal IgA antibodies. These antibodies, known as polymeric IgA1, have an aberrant O-glycosylation pattern, making them more prone to form immune complexes. 
• Mesangial Cell Activation: The deposited IgA immune complexes interact with mesangial cells, which are specialized cells located in the glomeruli. This interaction triggers a cascade of events, including the activation of complement system components and the release of pro-inflammatory cytokines. 
• Inflammatory Response: The activation of the complement system and the release of pro-inflammatory cytokines lead to the recuritment of inflammatory cells like macrophages, and neutrophils to the glomeruli. These cells release additional inflammatory mediators, perpetuating the immune response. 
• Glomerular Injury: The chronic inflammatory response and the presence of immune complexes in the glomeruli lead to glomerular injury. This can result in various pathological changes, including mesangial proliferation, glomerular sclerosis, and tubulointerstitial fibrosis. 
• Progressive Kidney Damage: Over time, the ongoing inflammation and glomerular injury can lead to progressive loss of kidney function. Some patients may develop nephrotic syndrome, characterized by significant proteinuria, edema, and hypoalbuminemia. Others may experience persistent microscopic hematuria or slowly declining kidney function. 

Etiology

• Aberrant IgA Production: The exact cause of Primary IgA Nephropathy is not fully understood, but it is believed to have an abnormal immune response. There is an overproduction of IgA antibodies, particularly the polymeric IgA1 subclass, which have abnormal O-glycosylation.  
• Genetic Predisposition: There is evidence to suggest a genetic component in the development of Primary IgA Nephropathy. However, the exact genes involved and their specific roles are still being investigated. 
• Environmental Factors: Environmental factors play important role in the development of Primary IgA Nephropathy. Infections, particularly respiratory and gastrointestinal infections, have been implicated as potential triggers for the abnormal immune response. Other factors such as dietary antigens and exposure to toxins or pollutants may also contribute to the disease process. 
• Immune Dysregulation: Primary IgA Nephropathy is considered an autoimmune or immune-mediated disease. There is an underlying dysregulation of the immune system, leading to the production of abnormal IgA antibodies and the formation of immune complexes. 

Genetics

Prognostic Factors

• Proteinuria: The severity of proteinuria is considered one of the important prognostic factors in Primary IgA Nephropathy. Higher levels of proteinuria at the time of diagnosis or persistent proteinuria over time are associated with an increased risk of adverse outcomes. 
• Hypertension: The presence of hypertension (high blood pressure) is another significant prognostic factor in Primary IgA Nephropathy. Uncontrolled or poorly controlled hypertension can lead to further kidney damage and accelerate the progression of the disease. 
• Histological Findings: The histological findings on kidney biopsy play a crucial role in determining the prognosis of Primary IgA Nephropathy. Certain features, such as the severity of mesangial proliferation, tubular atrophy, interstitial fibrosis, and the presence of crescents or sclerosis, are associated with a worse prognosis. 
• Renal Function: Patients with more advanced kidney disease and decreased glomerular filtration rate (GFR) are at higher risk of disease progression and renal failure. 
• Age at Diagnosis: The age at the time of diagnosis is also considered a prognostic factor. Younger patients, especially children, tend to have a more favorable prognosis compared to older adults. 
• Genetic and Molecular Factors: Emerging evidence suggests that specific genetic variations and molecular markers may have prognostic implications in Primary IgA Nephropathy. Certain genetic polymorphisms and markers related to the immune system and IgA production have been associated with different disease outcomes. 

Clinical History

Age Group: 

• Primary IgA Nephropathy can present at any age, but it most commonly affects patients in their 20s to 40s. It can occur in children and adults. 

Physical Examination

Physical examination findings in Primary Immunoglobulin A (IgA) Nephropathy may vary depending on the severity and progression of the disease. Here are some key aspects of the physical examination that may be relevant: 

Blood Pressure Measurement: 

• Hypertension is a common finding in patients with IgA nephropathy, especially in those with more advanced kidney damage. 
• The bp should be measured in both arms, and repeated measurements may be necessary to confirm the presence of hypertension. 

Edema: 

• Edema, which is swelling of the extremities and other body parts, may be present in patients with more advanced stages of IgA nephropathy. 
• The physician will examine the extremities, face, and sacral area for signs of edema. 

Auscultation of the Lungs: 

• Lung examination may be performed to assess for the presence of pulmonary edema, which can occur in severe cases of IgA nephropathy. 
• The physician may listen to the lungs using a stethoscope to detect any abnormal lung sounds, such as crackles or rales. 

Abdominal Examination: 

• Abdominal palpation may be performed to assess for the presence of enlarged kidneys or abdominal masses. 
• The physician may gently palpate the abdomen to evaluate the size, tenderness, or abnormal findings. 

Skin Examination: 

• Skin examination may reveal signs of systemic conditions associated with IgA nephropathy, such as purpura (small, reddish-purple spots on the skin) or skin rashes. 
• The physician will inspect the skin for any abnormal findings. 

Age group

Associated comorbidity

• Respiratory or Gastrointestinal Infections: Episodes of respiratory tract or gastrointestinal infections, particularly those caused by certain bacteria or viruses, may precede the onset of IgA nephropathy in some cases. 
• Autoimmune Disorders: There may be an increased prevalence of autoimmune disorders in individuals with IgA nephropathy, such as celiac disease, rheumatoid arthritis, or systemic lupus erythematosus. However, the causal relationship between these conditions and IgA nephropathy is not fully understood. 
• Family History: There is evidence of a genetic predisposition for IgA nephropathy, and it can sometimes occur in multiple family members, suggesting a familial or genetic component. 

Associated activity

Acuity of presentation

• Asymptomatic Hematuria: This is the most common presentation, where patients do not have any symptoms but may have blood detected in their urine during routine urinalysis. 
• Macroscopic Hematuria: Some individuals may experience visible blood in the urine, resulting in red or cola-colored urine. This usually occurs after an upper respiratory or gastrointestinal infection. 
• Nephrotic Syndrome: In some cases, IgA nephropathy can lead to nephrotic syndrome, characterized by significant proteinuria, edema, hypoalbuminemia, and high cholesterol levels. 

Differential Diagnoses

• Henoch-Schonlein purpura nephritis 
• Lupus nephritis 
• Post-infectious glomerulonephritis 
• IgA vasculitis  
• Alport syndrome 
• Thin basement membrane disease 
• Membranous nephropathy 
• Focal segmental glomerulosclerosis (FSGS) 
• Minimal change disease 
• C3 glomerulopathy 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

• The management of Primary Immunoglobulin A (IgA) Nephropathy aims to slow the progression of kidney damage, control symptoms, and prevent complications.  

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

• Blood pressure control: Maintaining optimal blood pressure is crucial in slowing the progression of kidney damage. Lifestyle modifications such as a regular exercise, low-sodium diet, weight loss, and avoiding tobacco and excessive alcohol consumption can help control blood pressure. 
• Proteinuria management: Reducing proteinuria is important in protecting the kidneys. This can be achieved through dietary protein restriction and the use of medications such as ACE inhibitors or angiotensin receptor blockers. 

• Immunosuppressive therapy: In selected cases with persistent or progressive kidney disease, immunosuppressive medications such as corticosteroids, immunosuppressants (e.g., azathioprine, mycophenolate mofetil), or rituximab may be considered. However, the use of immunosuppressive therapy should be individualized based on the patient’s clinical factors and potential side effects. 
• Antiplatelet agents: Low-dose aspirin may be prescribed to decreasse the risk of cardiovascular events in patients with IgA nephropathy and additional risk factors.

• Kidney biopsy: A kidney biopsy is essential for confirming the diagnosis of IgA nephropathy and assessing the severity of kidney damage. It helps guide treatment decisions and provides prognostic information. 
• Renal replacement therapy: In advanced cases of kidney failure, where conservative management is no longer sufficient, renal replacement therapy options such as hemodialysis, peritoneal dialysis, or kidney transplantation may be necessary. 

• Monitoring and observation: Regular monitoring of kidney function, blood pressure, proteinuria, and other relevant parameters is crucial in assessing disease progression and treatment response. 
• Follow-up care: Patients with IgA nephropathy require long-term follow-up to monitor kidney function, manage blood pressure, and detect and manage any complications or relapses. 
• Supportive care: Addressing associated symptoms, such as edema, electrolyte imbalances, and anemia, through supportive measures and appropriate interventions. 

Medication

Future Trends

Media Gallary

References

• https://www.niddk.nih.gov/health-information/kidney-disease/iga-nephropathy](https://www.nidd