Fibronectin Glomerulopathy - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Glomerulopathy is the type of disease that affects the glomeruli of the nephron (filtering unit of the kidney). Such diseases may involve inflammatory or non-inflammatory processes. Since glomerulitis exists for inflammatory diseases, glomerulopathy suggests a non-inflammatory condition. Glomerular diseases primarily affect the glomerulus. However, glomerular destruction renders the remaining nephrons nonfunctional, and further glomerular destruction can lead to decreased glomerular filtration rate, azotemia (buildup of nitrogenous products in the blood), and renal failure. Glomerular disease is an important cause of chronic renal failure in humans.

What Is Fibronectin Glomerulopathy?

Fibronectin glomerulopathy is a type of kidney disease that usually presents during early to mid-adulthood, but it can occur at any age. It ultimately leads to irreversible kidney failure (end-stage renal disease). Patients with fibronectin glomerulopathy usually have blood and excess protein in their urine (hematuria or proteinuria). They also have high blood pressure (hypertension). Some affected individuals develop renal tubular acidosis (excessive acid in renal tubes). This occurs when the kidneys cannot remove enough acid from the body, and the blood becomes extremely acidic. People with fibronectin glomerulopathy have large amounts of the protein fibronectin-1 deposited in structures called glomeruli in the kidneys. These structures are collections of small blood vessels within the kidney that filter all the waste products from the blood. The waste products are then released into the urine. Fibronectin-1 deposits impair glomerular filtration capacity.

Fibronectin glomerulopathy often develops into end-stage renal disease 15 to 20 years after signs and symptoms appear. Affected people can receive treatment in the form of a kidney transplant. Fibronectin glomerulopathy may recur (recur) after transplantation.

What Is the Cause of Fibronectin Glomerulopathy?

Fibronectin glomerulopathy is a type of genetic disease that is caused by mutations in the FN1 gene, and it is inherited in an autosomal dominant manner. That means one copy of the altered gene in each cell is enough to cause the disorder. In some of these cases, affected individuals have inherited the mutation from an affected parent. Mutations in the FN1 gene lead to the production of abnormal fibronectin-1 protein, which accumulates in kidney glomeruli. Although fibronectin-1 is abundant in glomeruli, the extracellular matrix that supports blood vessels is weakened because altered fibronectin-1 cannot support the continuous formation of the matrix. Without a strong cellular support network, glomeruli are less able to filter waste products. As a result, products that the body normally retains, such as proteins and blood, are released into the urine, and the blood is not properly filtered of acid. Over time, the kidney's ability to filter waste products decreases until they fail, leading to end-stage kidney disease.

What Are the Symptoms of Fibronectin Glomerulopathy?

Fibronectin glomerulopathy can occur at different ages but is most common during puberty or early adulthood. Its symptoms and features include:

• Severe swelling (edema), particularly around the eyes and in the ankles and feet.

• Foamy urine is a result of excess protein in the urine.

• Blood in the urine.

• Weight gain due to fluid retention.

• Fatigue.

• Loss of appetite.

• Decreased urine output.

• Fluid retention causes swelling of the feet, ankles, or feet.

• Difficulty breathing.

• Malaise.

• Confusion.

• Nausea.

• Weakness

• Irregular heartbeat.

• Chest pain or pressure.

• Seizures.

• Coma.

When to Get Help for Fibronectin Glomerulopathy?

An immediate medical checkup should be sought when a person notices any of the following signs.

• Nausea.

• Dizziness.

• Fever.

• Lethargy.

• Low urine output.

• Painful urination.

• Blood in the urine.

• Difficulty breathing.

How Is Fibronectin Glomerulopathy Diagnosed?

Fibronectin glomerulopathy is diagnosed in the ways listed below

• Histopathological Examinations - A renal biopsy is done to check for specimens showing lobular glomerulopathy and membranous proliferative glomerulonephritis-like lesions by light microscopy. Staining is done for Immunoglobulin and complement. Electron microscopy is done to show particulate deposits with fibril formation. Immunohistochemistry is done for fibronectin showing strong staining in the mesangium and peripheral loops.

• Blood Tests - Analysis of blood samples may reveal higher than expected levels of circulating waste products, the presence of antibodies indicative of an autoimmune disease, bacterial or viral infections, or blood sugar levels indicative of diabetes.

• Urine Tests - Urinalysis may show signs of poor kidney function, such as red blood cells or proteins that should not be present in the urine or white blood cells that are signs of inflammation.

What Is the Treatment of Fibronectin Glomerulopathy?

Fibronectin Glomerulopathy causes end-stage renal failure, which is the loss of more than 85 percent of kidney function. Acute renal failure due to fibronectin glomerulopathy is treated with dialysis. Dialysis uses a device that acts like an artificial external kidney to filter the blood. End-stage renal disease is a chronic kidney disease that can only be treated with regular renal dialysis or a kidney transplant. Some at-home remedies that may help with the management of this condition include:

• Reduce salt intake to prevent or minimize fluid retention, bloating, and high blood pressure.

• Decrease protein and potassium intake to slow the accumulation of waste products in the blood.

• Maintain a healthy weight.

• Avoid taking kidney-damaging medicines.

• Control blood sugar levels if having diabetes.

• Quit smoking.

• Avoid alcohol intake.

What Are the Complications of Fibronectin Glomerulopathy?

The complications of fibronectin glomerulopathy include:

• Accumulation of Fluid in the Body - Acute renal failure can cause accumulation of fluid in the lungs, causing shortness of breath.

• Severe Pain in the Chest - Inflammation of the membrane that covers the heart (pericardium) can cause chest pain.

• Weakness - An imbalance in the body's water and electrolytes (blood composition) can lead to muscle weakness.

• Permanent Damage of Kidneys - In some cases, acute renal failure can further lead to permanent loss of functioning of the kidney or the development of end-stage renal disease. Patients with end-stage renal disease most of the time require either permanent dialysis (a mechanical filtration process used to remove toxins and waste products from the body) or a kidney transplant to survive.

• Death- Acute renal failure can lead to loss of kidney function and eventual death.

How to Prevent Fibronectin Glomerulopathy?

Prevention of this condition is not possible as it is an inherited condition, but it can be managed in the following ways-

• Controlling blood sugar.

• Drink plenty of water and stay hydrated.

• Do yoga.

• Do regular exercise.

• Eat a healthy and balanced diet.

• Avoid sugar intake.

• Avoid taking nephrotoxic(kidney-damaging) medications.

Conclusion

Fibronectin glomerulopathy is a rare hereditary autosomal dominant glomerular disorder characterized by proteinuria (protein in the urine), microscopic hematuria (blood in the urine), hypertension (elevated blood pressure), massive glomerular deposits of fibronectin, and slow progression to end-stage renal failure. Due to the extremely low incidence of fibronectin glomerulopathy, the pathophysiology, genetic abnormalities, epidemiology, and mechanisms remain to be discovered. The condition can be managed with timely intervention and extra care at home. Improper care can lead to losing both kidneys. End-stage renal disease may lead to a kidney transplant and a need for dialysis.