Background

Berger’s disease, also known as IgA nephropathy, is a chronic kidney disorder characterized by the abnormal deposition of the immunoglobulin A (IgA) antibody in the glomeruli of the kidneys. It is the most common primary glomerulonephritis worldwide and can lead to kidney inflammation and damage over time.

IgA is a type of antibody that helps the body fight infections. In Berger’s disease, there is an abnormality in the production or clearance of IgA, leading to its accumulation in the glomeruli, which are the tiny blood vessels in the kidneys responsible for filtering waste products from the blood.

Epidemiology

Berger’s disease, also known as IgA nephropathy, is a relatively common form of primary glomerulonephritis worldwide. The epidemiology of Berger’s disease is influenced by various factors such as geographic location, ethnicity, and population-specific characteristics. Here are some key points regarding the epidemiology of Berger’s disease:

• Prevalence: Berger’s disease is recognized as the most common primary glomerulonephritis worldwide. The reported prevalence varies across different regions, ranging from 0.1 to 4.7 cases per 100,000 population. The highest prevalence rates have been observed in Asian populations, particularly in East Asian countries such as Japan and China.
• Age of Onset: Berger’s disease can affect individuals of all age groups, but it commonly manifests in younger individuals. The peak age of onset is typically between 15 and 35 years, with approximately 50% of cases presenting before the age of 30. However, the disease can occur at any age, including in children and older adults.
• Gender Distribution: Berger’s disease exhibits a slight male predominance, with a male-to-female ratio ranging from 2:1 to 3:1. This gender difference in prevalence is more pronounced in some populations, such as in Asian and Caucasian populations.
• Ethnic and Geographic Variations: The prevalence of Berger’s disease varies among different ethnic groups and geographical regions. It is more commonly observed in populations of East Asian descent, including Japanese, Chinese, and Korean populations. It is also relatively common in populations of European, Hispanic, and African descent. Lower prevalence rates have been reported in some Middle Eastern and African populations.
• Familial Cases: In a small proportion of cases, Berger’s disease has a familial pattern, suggesting a genetic predisposition. Family members of individuals with the disease may have a higher risk of developing IgA nephropathy compared to the general population.
• Risk Factors: Several risk factors have been identified that may contribute to the development of Berger’s disease. These include a history of upper respiratory tract infections or gastrointestinal infections preceding the onset of the disease, as well as genetic factors. Certain human leukocyte antigen (HLA) genotypes, particularly HLA-DRB103 and HLA-DQB102, have been associated with an increased risk of Berger’s disease.

Anatomy

Pathophysiology

The pathophysiology of Berger’s disease, also known as IgA nephropathy, involves the abnormal deposition of the immunoglobulin A (IgA) antibody in the glomeruli of the kidneys. This deposition triggers an immune response and inflammation, leading to kidney damage. Here is a detailed explanation of the pathophysiology:

• Abnormal IgA Production: In Berger’s disease, there is an abnormality in the production or clearance of IgA antibodies. It is believed that certain environmental triggers, such as infections or exposure to antigens, can cause the production of abnormal IgA molecules or lead to increased levels of circulating IgA.
• IgA Deposition in the Glomeruli: The abnormal IgA antibodies accumulate in the glomeruli of the kidneys. The glomeruli are the specialized structures responsible for filtering waste products from the blood and maintaining the balance of fluids and solutes.
• Formation of Immune Complexes: The deposited IgA antibodies form immune complexes within the glomeruli. These immune complexes consist of IgA antibodies bound to antigens, such as bacterial or viral particles.
• Activation of the Complement System: The immune complexes trigger the activation of the complement system, which is part of the body’s immune response. The complement system consists of a group of proteins that work together to promote inflammation and destroy foreign substances.
• Inflammatory Response: The activation of the complement system leads to the recruitment of inflammatory cells, such as neutrophils and macrophages, to the glomeruli. These cells release inflammatory mediators, such as cytokines and chemokines, which further promote inflammation and tissue damage.
• Glomerular Injury and Scarring: The chronic inflammation and immune response within the glomeruli cause damage to the delicate structures involved in the filtration process. Over time, this damage leads to scarring and thickening of the glomeruli, impairing their ability to function properly.
• Altered Glomerular Permeability: The deposition of immune complexes and the inflammatory process disrupt the normal filtration barrier of the glomeruli. This can result in increased permeability, allowing the leakage of red blood cells and protein into the urine, leading to hematuria (blood in the urine) and proteinuria (excessive protein in the urine).
• Disease Progression: The ongoing inflammation and glomerular injury can lead to progressive kidney damage, ultimately resulting in chronic kidney disease (CKD) or end-stage renal disease (ESRD) in some cases. The extent of kidney damage and the rate of disease progression can vary among individuals, with some experiencing a more benign course and others experiencing rapid deterioration of kidney function.

Etiology

The exact etiology of Berger’s disease, also known as IgA nephropathy, is not fully understood. However, it is believed to involve a combination of genetic predisposition, abnormal IgA production, and environmental triggers. Here are the key factors implicated in the etiology of Berger’s disease:

• Genetic Factors: There is evidence to suggest a genetic predisposition to Berger’s disease. Certain human leukocyte antigen (HLA) genotypes have been associated with an increased risk of developing the disease. HLA molecules play a critical role in immune regulation and antigen presentation. The HLA region on chromosome 6 has been found to be linked to susceptibility to IgA nephropathy, particularly HLA-DRB103 and HLA-DQB102 alleles. However, it is important to note that genetic factors alone are not sufficient to cause the disease, and additional environmental triggers are likely required.
• Abnormal IgA Production and Clearance: In Berger’s disease, there is an abnormality in the production or clearance of the immunoglobulin A (IgA) antibody. It is thought that certain environmental triggers, such as infections or exposure to antigens, can lead to the production of abnormal IgA molecules or increased levels of circulating IgA. The abnormal IgA antibodies then deposit in the glomeruli of the kidneys, initiating an immune response and inflammation.
• Environmental Triggers: Environmental factors are believed to play a role in the development and progression of Berger’s disease. Infections, particularly respiratory or gastrointestinal infections, have been identified as potential triggers. It is hypothesized that these infections stimulate the immune system, leading to an abnormal IgA response and subsequent glomerular deposition. However, the exact mechanisms by which infections contribute to the development of Berger’s disease are not fully understood.
• Mucosal Immune System Dysfunction: The mucosal immune system, which includes the immune cells and tissues lining the respiratory and gastrointestinal tracts, may play a role in the development of Berger’s disease. It is postulated that dysfunction or dysregulation of the mucosal immune system may contribute to abnormal IgA production and subsequent deposition in the kidneys.

Genetics

Prognostic Factors

The prognosis of Berger’s disease (IgA nephropathy) can vary widely among individuals and is influenced by several factors. It is important to note that Berger’s disease is a chronic condition, and its course can be unpredictable. Here are some factors that can affect the prognosis:

• Proteinuria and Glomerular Filtration Rate (GFR): The level of proteinuria (excessive protein in the urine) and the rate of decline in the glomerular filtration rate (GFR) are significant predictors of prognosis. Higher levels of proteinuria and a more rapid decline in GFR are associated with a worse prognosis and an increased risk of kidney failure.
• Blood Pressure Control: Maintaining optimal blood pressure is crucial in managing Berger’s disease and slowing the progression of kidney damage. Poorly controlled hypertension can contribute to the worsening of kidney function and increase the risk of complications.
• Histological Findings: The specific findings observed on kidney biopsy can provide additional prognostic information. Features such as the degree of glomerular scarring, tubular atrophy, interstitial fibrosis, and crescent formation can help determine the severity and prognosis of the disease.
• Age at Diagnosis: The age at which Berger’s disease is diagnosed can also impact the prognosis. Younger patients tend to have a slower progression of the disease, while older individuals may experience more rapid kidney function decline.
• Persistent or Recurrent Hematuria: Persistent or recurrent episodes of hematuria (blood in the urine) despite treatment can indicate a higher risk of disease progression and a worse prognosis.
• Comorbidities: The presence of comorbidities, such as diabetes, hypertension, or other kidney diseases, can influence the prognosis of Berger’s disease. Managing these conditions appropriately is essential for optimizing outcomes.
• Response to Treatment: The response to treatment can vary among individuals. Some patients may experience a favorable response to immunosuppressive therapy or blood pressure control, leading to better outcomes and a slower progression of the disease.

Clinical History

Clinical history

When obtaining the clinical history of a patient with Berger’s disease (IgA nephropathy), healthcare providers typically inquire about various aspects related to the patient’s symptoms, medical history, and potential risk factors. Here are some key points that may be covered during the clinical history:

• Urinary Symptoms: Inquire about any urinary symptoms the patient may have experienced, such as hematuria (blood in the urine), which may be microscopic or gross (visible to the naked eye). Determine the frequency and duration of hematuria episodes and whether it is associated with other symptoms like flank pain or discomfort during urination.
• Proteinuria: Assess the presence and severity of proteinuria, which refers to excessive protein in the urine. Inquire about any foamy or frothy urine, as it can be indicative of significant proteinuria.
• Systemic Symptoms: Determine if the patient has experienced any systemic symptoms, such as fatigue, malaise, weight loss, or fever. These symptoms may be associated with the underlying immune response and inflammation seen in Berger’s disease.
• History of Infections or Triggers: Investigate whether the patient has had any recent upper respiratory tract infections, gastrointestinal infections, or other infections preceding the onset of symptoms. Infections are considered potential triggers for the abnormal immune response seen in Berger’s disease.
• Family History: Inquire about a family history of kidney disease or any other relevant medical conditions, as there is evidence of a genetic component to Berger’s disease. Determine if any relatives have been diagnosed with IgA nephropathy or other kidney disorders.
• Medications and Medical History: Assess the patient’s current and past medications, including over-the-counter drugs and herbal supplements, as certain medications may contribute to kidney damage or affect renal function. Obtain information about any relevant medical history, including pre-existing conditions such as diabetes, hypertension, or autoimmune disorders.
• Lifestyle Factors: Inquire about the patient’s lifestyle habits, such as smoking, alcohol consumption, and dietary patterns. These factors may not directly cause Berger’s disease but can influence disease progression and management.
• Renal Function and Blood Pressure: Assess the patient’s history of kidney function and blood pressure measurements, if available. Document any previous kidney function tests, such as serum creatinine and estimated glomerular filtration rate (eGFR), as well as blood pressure readings.

Physical Examination

Physical examination

During the physical examination of a patient with Berger’s disease (IgA nephropathy), healthcare providers typically assess various aspects of the patient’s overall health and look for signs that may indicate kidney involvement or complications. Here are some key points that may be covered during the physical examination:

• Blood Pressure Measurement: Measure the patient’s blood pressure to assess for hypertension, which is commonly associated with kidney disease. Elevated blood pressure levels may indicate kidney damage and the need for appropriate management.
• Edema: Examine the patient for the presence of edema, which is swelling caused by fluid retention. Edema can occur in various parts of the body, but common areas to assess include the lower extremities, hands, and face. Edema may be indicative of fluid imbalance and impaired kidney function.
• Skin Examination: Inspect the skin for any signs of purpura, which are small purple spots or patches caused by bleeding under the skin. Purpura may be associated with systemic vasculitis, such as Henoch-Schönlein purpura, which can mimic or coexist with Berger’s disease.
• Abdominal Examination: Perform a thorough abdominal examination, including palpation, to assess for any tenderness or abdominal masses. Abdominal pain or discomfort may be present in some patients, particularly if gastrointestinal involvement is suspected.
• Joint Examination: Assess the joints for signs of arthritis or joint pain. Joint involvement can be seen in certain forms of vasculitis, such as Henoch-Schönlein purpura, which may present with similar symptoms to Berger’s disease.
• Auscultation of the Heart and Lungs: Listen to the heart and lungs with a stethoscope to evaluate for any abnormal sounds or murmurs. Cardiac and pulmonary complications can occur in advanced cases of kidney disease.
• Neurological Examination: Perform a basic neurological examination, including assessing for any signs of peripheral neuropathy or neurological deficits. These manifestations can occur in rare cases of IgA vasculitis with nervous system involvement.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential diagnosis

When evaluating a patient with suspected Berger’s disease (IgA nephropathy), it’s important to consider other conditions that can cause similar clinical features. The following are some differential diagnoses to consider:

• Henoch-Schönlein Purpura (HSP): HSP is a systemic vasculitis that often presents with palpable purpura (small purple spots) on the skin, joint pain, gastrointestinal symptoms, and kidney involvement. Like Berger’s disease, HSP is characterized by IgA deposition, but it involves multiple organs, including the skin, joints, and gastrointestinal tract.
• Systemic Lupus Erythematosus (SLE): SLE is a chronic autoimmune disease that can affect multiple organ systems, including the kidneys. Lupus nephritis, the kidney manifestation of SLE, can present with similar features to Berger’s disease, including hematuria, proteinuria, and decreased kidney function. A comprehensive evaluation with laboratory tests and clinical criteria can help differentiate between the two conditions.
• Alport Syndrome: Alport syndrome is a genetic disorder that affects the basement membrane of the kidney, leading to progressive kidney disease. It often presents with hematuria, proteinuria, and hearing loss. Unlike Berger’s disease, Alport syndrome typically shows a characteristic pattern of glomerular basement membrane thinning and splitting on kidney biopsy.
• Thin Basement Membrane Disease (TBMD): TBMD is a genetic disorder characterized by thinning of the glomerular basement membrane. It may present with isolated hematuria, often in families with a history of recurrent microscopic or gross hematuria. Distinguishing TBMD from Berger’s disease may require kidney biopsy to evaluate the thickness of the basement membrane.
• Membranoproliferative Glomerulonephritis (MPGN): MPGN is a type of glomerulonephritis that involves inflammation and thickening of the glomerular basement membrane. MPGN can present with hematuria, proteinuria, and decreased kidney function, similar to Berger’s disease. Careful evaluation of kidney biopsy findings and additional laboratory tests, such as complement levels, can help differentiate between MPGN and Berger’s disease.
• IgA Vasculitis (formerly Henoch-Schönlein purpura): IgA vasculitis is a systemic vasculitis characterized by IgA immune complex deposition. It often presents with skin rash, joint pain, gastrointestinal symptoms, and kidney involvement. It can sometimes be challenging to differentiate from Berger’s disease, but a comprehensive evaluation considering clinical features, biopsy findings, and additional investigations can help distinguish between the two conditions.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The treatment of Berger’s disease (IgA nephropathy) aims to manage symptoms, slow the progression of kidney damage, and reduce the risk of complications. The specific treatment approach may vary depending on the severity of the disease, the presence of symptoms, and individual patient factors. Here are some common strategies used in the treatment of Berger’s disease:

• Blood Pressure Control: Maintaining optimal blood pressure is crucial in managing Berger’s disease. Medications called angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs) are commonly prescribed to help control blood pressure and reduce proteinuria, even in the absence of hypertension.
• Immunosuppressive Therapy: In certain cases where there is significant kidney damage or progressive disease, immunosuppressive medications may be considered. These medications, such as corticosteroids or immunosuppressants like cyclophosphamide or azathioprine, aim to reduce the immune response and inflammation in the kidneys. The decision to use immunosuppressive therapy depends on various factors, including the severity of the disease and the risk of adverse effects.
• Supportive Care: Supportive measures play an important role in managing Berger’s disease. These include maintaining a healthy lifestyle with regular exercise, a balanced diet, and weight management. Dietary modifications, such as reducing sodium intake, may be recommended to manage fluid retention and blood pressure. It’s also important to manage other medical conditions, such as diabetes or high cholesterol, to minimize their impact on kidney function.
• Monitoring and Surveillance: Regular monitoring of kidney function, blood pressure, proteinuria, and urinary abnormalities is essential to assess disease progression and response to treatment. Healthcare providers may recommend periodic blood tests, urine tests, and imaging studies to evaluate kidney function and detect any complications.
• Management of Complications: If complications arise, such as nephrotic syndrome or advanced kidney disease, additional interventions may be necessary. These can include the use of diuretics to manage fluid retention, anticoagulants to prevent blood clots, or referral for specialized interventions like kidney biopsy or consultation with a nephrologist.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Future Trends

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK499998/