IgA nephropathy (Berger's disease)

What is Berger's disease?

IgA nephropathy can also be referred to as Berger's disease. It’s a type of kidney condition that damages the small tiny filters of the kidneys. IgA nephropathy arises when the antibodies known as immunoglobulin A (IgA) accumulate in the kidneys. Immunoglobulin forms part of the normal areas of the body's immune system that facilitate infection and microorganisms fighting function. Patients with IgA nephropathy usually have a defense mechanism version of immunoglobulin A.

A doctor called Berger was the first to describe the disease, so it also carries the name Berger disease.

IgA nephropathy is a kind of glomerulonephritis characterized by IgA immunoglobulin accumulation in the glomerular basement membrane. Hematuria and renal insufficiency are caused by immune-mediated damage to the basement membrane.

Overall, IgA nephropathy causes inflammation in the kidneys that can alter the normal function of blood filtration with time. IgA nephropathy often varies among the patients; however, it can gradually progress over the years.

The inflammation causes your kidneys to leak blood and protein, and over time, your kidneys might lose function and eventually die. In certain situations, the disease appears to cluster in specific families and regions of the world. It is uncommon among persons of African descent. Some experts believe that hereditary factors may play a role in the disease's development.

Epidemiology

Although IgA nephropathy is a prevalent illness, data on prevalence is imprecise due to the need for a kidney biopsy to confirm the diagnosis. Not all patients are subjected to a biopsy to confirm the diagnosis and instead are treated conservatively.

In the United States, IgA nephropathy is seen in around 10% of renal biopsies. IgA nephropathy is seen in 40% of renal biopsies in Asia and 20% of renal biopsies in Europe.

The high incidence is considered to be attributable to early identification of hematuria during screening and intensive treatment regimens. The illness is more frequent in children and young adults, with a male preponderance.

Males are more likely than females to develop IgA nephropathy. Almost all studies reveal at least a 2:1 male preponderance, with reported ratios as high as 6:1. White patients in Northern Europe and the United States have a greater masculine preference.

IgA nephropathy can affect people of all ages, although it is more frequent in their second and third decades. At the time of diagnosis, eighty percent of patients are between the ages of 16 and 35. In youngsters under the age of ten, the condition is uncommon.

Pathophysiology

According to current thinking, IgA nephropathy is caused by multiple steps. The initial 'hit' is a genetically vulnerable host who is inclined to producing an unbalanced immunological response. A next step is a precipitating event that results in an immunological assault. Infections are a possible cause of IgA nephropathy.

Mild mucosal infections, persistent pathogen exposure, and improper handling of commensals in the gut have all been proposed as causes of IgA nephropathy's aberrant immune response.

Damage to the basement membrane causes ultrafiltration of bigger molecules, resulting in hematuria. The mechanism of how some people have asymptomatic hematuria while others suffer quickly increasing glomerulonephritis that leads to renal failure is unknown.

Causes of IgA Nephropathy

IgA nephropathy is an autoimmune illness that causes the glomerular basement membrane to be destroyed by antibodies. Usually, an infectious condition precedes the nephropathy, causing a dysregulated immune response, whereas IgA nephropathy is not caused by an infectious disease.

The majority of instances with IgA nephropathy are idiopathic, although the disease's start or aggravation is frequently preceded by a respiratory tract infection. Some bacteria, such as Haemophilus parainfluenzae, have been linked to it.

Every person has two bean-shaped kidneys located in the abdomen behind the peritoneum on both sides of the vertebral column. Each kidney comprises small tiny blood vessels that play a major role in filtering wastes from the blood as they flow via the kidneys.
On the other hand, immunoglobulin (IgA) is a significant antibody responsible for fighting off infections and harmful pathogens. For patients with IgA nephropathy, immunoglobulin A or IgA piles up in the glomeruli. Over time, it causes inflammation and slowly affects the normal filtering process.

Medical researchers are not certain of the actual cause of IgA accumulations in the kidney. However, they believe that it’s usually linked to;

Infections such as viral infections (HIV) and bacterial infections

IgA nephropathy has been reported in patients with HIV infection, both whites and blacks, despite the rarity of typical IgA nephropathy in the black population. Clinically, patients have hematuria, proteinuria, and, possibly, renal insufficiency.

Histologically, mesangial proliferative glomerulonephritis to collapsing glomerulosclerosis with mesangial IgA deposits are seen. Several individuals exhibited IgA antibodies against viral proteins circulating in their blood.

Genetics: According to research, IgA nephropathy is prevalent in certain families or ethnic groups

Liver diseases, including liver cirrhosis and chronic hepatitis B or C

Glomerular IgA deposition is a frequent observation in individuals with cirrhosis, occurring in more than one-third of cases. Impaired clearance of IgA-containing complexes by Kupffer cells is associated with liver illness, predisposing individuals to IgA accumulation in the kidney.

Glomerular IgA deposits are frequent in late liver disease, although most adults have no clinical symptoms of glomerular illness, but up to 30% of children may have asymptomatic hematuria or proteinuria. These abnormalities generally go away following a successful liver transplant.

Celiac disease

Glomerular IgA deposition can occur in up to one-third of gluten enteropathy patients. The majority of these people have no clinical symptoms of the illness. However, IgA nephropathy and gluten hypersensitivity are linked, and removing gluten from these individuals' diets has resulted in clinical and immunological improvement of their renal illness.

Berger's disease symptoms

The clinical symptoms of IgAN are diverse, ranging from asymptomatic microscopic hematuria to rapidly progressive GN.

During the early stages, a person with IgA nephropathy doesn’t always experience any signs and symptoms. At times, the condition can even go unnoticed for up to years and decades. However, doctors can sometimes detect the disease during regular tests. This is if the results show the presence of red blood cells and proteins in the urine that can’t easily be noticed without using a microscope.

Regardless, some of the common IgA nephropathy symptoms and signs can include the following;

Tea or cola-colored urine due to the presence of red blood cells in the urine.
Constant episodes of tea or cola-colored urine. At times, you may notice visible blood in the urine.
Edema; swelling of the feet or hands
Hypertension or high blood pressure
Pain in either the one or the two sides of the back, underneath the ribs
Urine associated with foam that occurs due to protein leakage into the urine; proteinuria
Chronic renal failure

Diagnosing IgA Nephropathy

In most cases, IgA nephropathy is usually detected during a regular test if the doctor notices blood or protein in the urine. Alternatively, traces of blood in the urine can indicate IgA nephropathy. However, to rule out the situation, the doctor can conduct a number of tests and procedures. This can also help identify the type of kidney disease.

IgA nephropathy diagnostic tests and procedures can thus include the following;

Urine tests

A thorough urinalysis of a first-void urine sample is the first step in verifying the diagnosis.

The presence of protein or blood in the urine is usually the most common sign of IgA nephropathy disease. The healthcare provider can detect this when conducting overall routine check-ups. Therefore, once the doctor notices blood or protein in the urine, they can recommend 24 hours urine collection. This helps check the kidney functions and further assess the suspected condition.

Glomerular damage is indicated by the presence of red cells and red cell casts. Proteinuria is diagnosed by measuring the protein to creatinine ratio in urine or the 24-hour urinary protein excretion. To assess renal function, serum creatinine and eGFR are measured.

A kidney biopsy is used to confirm the diagnosis. Renal histology is studied using light microscopy, electron microscopy, and immunofluorescence. The gold standard for diagnosis is immunofluorescence, which shows IgA deposits in the glomerular basement membrane.

Blood tests

The aim of blood tests is to check if the cause of blood and protein traces in the urine is IgA nephropathy. The test results will indicate an increase in the blood level of creatinine waste product if you have the disease.

Kidney biopsy

This is the most effective procedure that doctors often suggest to confirm IgA nephropathy diagnosis. A kidney biopsy involves the removal of small samples of kidney tissue using a specialized needle. The doctor will then examine the sample further under a microscope.

Iothalamate clearance test

This diagnostic test involves using a specialized contrast agent to assess kidney functions. It can include how well they filter waste products. The doctor can sometimes recommend iothalamate clearance tests if other procedures are not effective.

Proteinuria

Proteinuria without microscopic hematuria is uncommon in IgA nephropathy. Mild proteinuria is very common.

Nephrotic-range proteinuria is rare, occurring in just 5% of IgA nephropathy patients, and is more common in children and adolescents. Proteinuria in the nephrotic range can be found early in the illness's progression as well as in individuals with severe disease.

IgA deposition with widespread proliferative glomerular lesions or minimal-change light microscopic findings is common in patients with severe proteinuria and nephrotic syndrome.

Acute kidney injury

Acute kidney injury with edema, hypertension, and oliguria, occurs in fewer than 5% of patients. It can develop from either of the following two distinct mechanisms:

Acute severe immune injury can manifest as necrotizing glomerulonephritis and crescent formation
Alternatively, only mild glomerular injury is observed with gross hematuria, and kidney injury is presumably due to tubular occlusion by RBCs; this is reversible, and renal function recovers with supportive measure

IgA Nephropathy Treatment

The initial step in treating IgA nephropathy is to confirm the diagnosis, followed by a kidney biopsy. Secondary causes of IgA nephropathy must be excluded. Proteinuria, eGFR, blood pressure, and histological appearance all play a role in the therapeutic strategy. The goal of treatment is to promote remission and prevent problems from developing.

Basically, there is no specific cure or a certain course of IgA nephropathy treatment. Depending on the nature of the condition, the doctor can administer several medications. This is to help slow down the progress of the disease while managing the associated symptoms. In other cases, they can recommend monitoring the condition to enable them to determine if it’s advancing or becoming worse.

All patients should be provided supportive treatment, which includes renin-angiotensin system inhibition and salt restriction in the diet. Tonsillectomy is only recommended for people who have recurrent tonsil infections.

The common types of medication to address IgA nephropathy can include the following;

High blood pressure drugs

The aim of high blood pressure medication is to help manage blood pressure levels and limit the loss of protein. In such cases, the doctor often administers angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors.

Renal transplantation is an option for those who advance to end-stage renal disease (ESRD). The danger of IgA nephropathy in the transplanted kidney remains. In allografts, treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker may slow the course of recurrent illness.

Immunosuppressants

At times, the doctor can recommend corticosteroid medications, including prednisone and similar potent medicines. This helps suppress the body's immune system response and prevents it from attacking or reacting against the glomeruli. However, it’s essential to note that the drug is usually associated with adverse side effects. It can include high blood pressure, a higher risk of infection, or increased blood sugar level.

Omega-3 fatty acids

Essential fatty acid deficiencies have been seen in IgA nephropathy, and fish oil is high in long-chain omega-3 polyunsaturated fatty acids. As a result, prostaglandins and leukotrienes are changed and less physiologically efficacious, and platelet aggregation is decreased. Although there is no evidence to support the use of fish oil as a stand-alone therapy, some doctors mix it with other treatments.

You can always consider these fats to help with IgA nephropathy conditions. Omega-3 fatty acids are mostly present in fish oil supplements and can help ease inflammation and pain in the glomeruli. Furthermore, it doesn’t cause any adverse side effects. However, it’s essential to first consult with the physician before taking the supplements.

Statin therapeutic drugs

To manage high cholesterol, doctors often administer cholesterol-reducing drugs. The aim of these medications involves controlling and slowing down the kidney damage progress.

Diuretics drugs

The purpose of this medication involves removing extra fluid in the blood. This eventually enhances overall blood pressure control.

The general objective of using these medications is to help avoid or prevent the necessity of kidney transplants or dialysis. However, in certain circumstances, kidney transplants or dialysis might be required, especially if the condition is advanced.

Diet

A low-antigen diet, which includes limiting dietary gluten and eliminating meats and dairy products, has been advised to reduce mucosal antigen exposure. However, it has not been demonstrated to sustain renal function.

Low-protein diets have been suggested as a way to halt the development of several nephropathies. There have been no major trials that specifically investigate the impact of low-protein diets in delaying the loss in renal function in IgA nephropathy.

Kidney Transplantation

In people with IgA nephropathy, kidney transplantation is beneficial, however, the condition commonly recurs following transplantation (20-60 percent ). The greater recurrence rates in transplantation from live related donors imply hereditary predisposition to the illness and significant danger, particularly if the disease is aggressive with crescents and treatment is challenging.

Measures to Manage IgA Nephropathy

While there is no specific treatment or ways of addressing IgA nephropathy, managing it may be the best alternative. Managing IgA nephropathy also enables you to live a healthier life and prevent associated risks and complications.

The best way of slowing down the progress of IgA nephropathy disease is through diet changes or adjustments. For instance, you can consider;

Reducing intake of sodium
Limiting the amount of protein intake in the regular diet
Consuming a diet with lower cholesterol or saturated fats
Adjusting the regular diet by including omega-3 fatty acid sources such as walnuts, canola oil, fish oil supplements, flaxseeds, and cod liver oil.

Although patients with IgA nephropathy can manage the condition, medical experts have not found effective ways of preventing it. However, individuals with a family history of such disease should consult a healthcare provider. Through this, they can find out the essential steps to take to ensure the kidneys remain healthy. It can be managing blood pressure and maintaining blood cholesterol at healthier levels.

Differential Diagnosis

Clinically, the diagnosis is typically obvious, and tests can quickly confirm it. The differential diagnosis includes lupus nephritis, nephrotic syndrome, membranoproliferative glomerulonephritis, and Henoch-Schönlein purpura.

Hematuria can be caused by cancers ranging from the kidneys to the urethra, as well as local trauma, urolithiasis, and even urinary tract infections. Because these diseases manifest in such a variety of ways, they rarely offer diagnostic challenges.

Buerger's disease prognosis

IgA nephropathy is the most common cause of CKD and renal failure.

IgA nephropathy frequently has a benign course. Others develop end-stage renal disease (ESRD) gradually, with the prevalence of ESRD rising with age. Based on the Oxford classification, the prognosis is somewhat predictable. Furthermore, on presentation, nephrotic range proteinuria, hypertension, a high serum creatinine level, and extensive intestinal fibrosis of the kidneys indicate a bad prognosis.

Predictors of poor renal outcomes include the following:

High serum creatinine level (>120 mmol/L) at presentation
Hypertension (diastolic >95 mm hg or need for antihypertensive treatment)
Proteinuria: Urinary protein excretion < 1 g/24 hr is associated with 56% renal survival and >3.5 g/24 hr with 7% renal survival
Extensive interstitial fibrosis and tubular atrophy on renal biopsy

Complications of IgA Nephropathy

IgA nephropathy disease affects people in varying ways. While some may experience severe symptoms and complications, others can have the condition for several years without experiencing any issue. Most IgA nephropathy cases can go unnoticed or undiagnosed for a very long period.

However, depending on the nature of the disease, extent, and overall health, some individuals can various complications, including;

Despite the fact that only a small number of individuals with IgA glomerulonephritis develop ESRD, IgA glomerulonephritis is a common cause of ESRD.
High cholesterol: IgA nephropathy is usually associated with cholesterol. As the levels of cholesterol get high, it increases the risk of suffering a heart attack.
High blood pressure: IgA accumulation can cause severe damages to the kidney; with time, this can increase blood pressure level. As the blood pressure gets higher, it can result in more kidney damages which can be irreversible.
Acute kidney failure: IgA nephropathy affects kidney functions, including blood filtration ability. This causes the waste product to rapidly accumulate in the blood, resulting in acute kidney failure.
Chronic kidney disease: IgA nephropathy condition can gradually hinder the normal functions of the kidney. With time, the kidneys will no longer function resulting in chronic kidney disease. In such a case kidney transplant or permanent dialysis may be required to survive.
Nephrotic syndrome: This is a health condition associated with a series of problems that arises due to glomeruli damages. These problems include increased cholesterol and lipids, high levels of protein in the urine, reduced levels of blood protein, swelling of the feet, abdomen, or eyelids.

See more about Everything about kidney failure

Differentiation of nephropathy from urolithiasis

Nephrolithiasis is a common disease associated with the presence of lithiasis or stones in the kidneys or in the excretory tract.

See more about Urinary Stone Disease Facts

Mortality/Morbidity

In most situations, this condition is believed to be harmless. However, many people are at risk of gradual development to ESRD, which occurs in roughly 15% of patients within 10 years and 20% within 20 years, depending on how the illness is characterized.

End-stage renal illness is well recognized to be a risk factor for the development of kidney cancer in the native kidney of patients requiring renal replacement therapy.

See more about Kidney Cancer Facts

Conclusion

IgA nephropathy (Berger’s disease) is a kidney disease that affects most people in the world. It mainly occurs due to the build-up of IgA deposits in the kidneys and usually results in kidney tissue damages. Although this condition progresses at a relatively slower rate in most people, it can be associated with adverse complications in the long run. This includes high blood pressure, acute and chronic kidney failure, and dead.