NEPHRITIC AND NEPHROTIC SYNDROME EXPLAINED

Introduction

Nephritic syndrome and nephrotic syndrome are two different kidney disorders that affect the glomeruli, which are tiny filters in the kidneys responsible for filtering blood and removing waste products.

Nephritic syndrome is a type of kidney disorder that occurs when the glomeruli become inflamed and damaged, causing blood and protein to leak into the urine. Symptoms may include blood in the urine, high blood pressure, swelling in the legs, and reduced urine output. Common causes of nephritic syndrome include autoimmune disorders, infections, and certain medications.

Nephrotic syndrome, on the other hand, is a condition in which the glomeruli become damaged and allow large amounts of protein to leak into the urine. This results in low levels of protein in the blood, causing edema (swelling) in the legs, ankles, feet, and sometimes the abdomen. Other symptoms may include foamy urine, fatigue, and weight gain. Causes of nephrotic syndrome include diabetes, lupus, and certain infections.

Both nephritic and nephrotic syndromes require prompt diagnosis and treatment to prevent complications such as kidney failure. Treatment may involve medications to control inflammation and blood pressure, as well as dietary changes to reduce protein and sodium intake. In some cases, kidney transplant may be necessary.

 

The mechanism of nephritic syndrome is complex and involves a combination of immune system dysfunction and damage to the glomeruli. In many cases, the condition is caused by an immune response to an infection, such as strep throat, that triggers the formation of immune complexes in the bloodstream. These immune complexes can become lodged in the glomeruli, triggering an inflammatory response that damages the glomeruli and causes them to leak protein and blood into the urine.

Other possible causes of nephritic syndrome include autoimmune disorders such as lupus, as well as certain genetic disorders and medications. In some cases, the cause of the condition may be unknown.

The manifestations of nephritic syndrome may vary depending on the underlying cause and the severity of the condition. Common symptoms include:

1. Hematuria: This is the most common symptom of nephritic syndrome and is characterized by the presence of blood in the urine. The urine may appear pink, red, or brown.
2. Proteinuria: This is another common symptom of nephritic syndrome and is characterized by the presence of excess protein in the urine. This can lead to swelling and fluid retention in the body.
3. Hypertension: High blood pressure is common in people with nephritic syndrome and can be a sign of kidney damage.
4. Decreased GFR: A decreased GFR, which is a measure of kidney function, is also common in people with nephritic syndrome. This can lead to fatigue, weakness, and other symptoms associated with kidney failure.

Treatment for nephritic syndrome typically involves addressing the underlying cause of the condition, as well as managing the symptoms. This may include medications to control blood pressure and reduce inflammation, as well as dietary changes to reduce the workload on the kidneys. In some cases, more aggressive treatments such as immunosuppressive therapy or dialysis may be necessary to manage the condition.

 

Nephrotic Syndrome Components

The main components of nephrotic syndrome include:

1. Proteinuria: Large amounts of protein in the urine due to damage to the glomeruli, which normally filter out excess protein from the blood.
2. Hypoalbuminemia: Low levels of albumin in the blood, which can lead to fluid accumulation in the body (edema).
3. Hyperlipidemia: Elevated levels of cholesterol and triglycerides in the blood due to the liver’s increased production of lipids in response to hypoalbuminemia.
4. Edema: Swelling in various parts of the body, particularly in the legs and feet, due to the accumulation of fluid in the tissues.
5. Fatigue and weakness: These symptoms can result from the loss of protein in the urine and the resulting malnutrition.

Other symptoms that may occur in nephrotic syndrome include:

6. Decreased urine output: This can occur due to reduced blood flow to the kidneys or damage to the tubules that reabsorb water from the urine.
7. Foamy urine: This is a result of the excess protein in the urine, which causes it to appear frothy.
8. High blood pressure: This can occur due to the retention of salt and water in the body.
9. Loss of appetite: This can occur due to a buildup of waste products in the blood, which can cause nausea and vomiting.

It is important to note that the severity and specific components of nephrotic syndrome can vary depending on the underlying cause.

 

The following are some types of glomerulonephritis associated with nephritic syndrome:

• IgA nephropathy.
• Post-infectious glomerulonephritis.
• Membranoproliferative glomerulonephritis.
• Rapidly progressive glomerulonephritis.
• Crescentic glomerulonephritis.
• Focal segmental glomerulosclerosis (FSGS) with nephrotic-range proteinuria and features of nephritic syndrome.

These types of glomerulonephritis may cause symptoms such as blood in the urine, proteinuria, high blood pressure, edema, and decreased urine output. Treatment depends on the underlying cause and severity of the condition and may include medications to control blood pressure and inflammation, as well as dietary changes to reduce proteinuria and prevent further kidney damage.

 

The pathogenesis of nephrotic syndrome involves complex interactions between various factors, including immune dysregulation, genetic predisposition, environmental factors, and podocyte injury.

Podocytes are specialized cells that are found in the glomeruli of the kidneys, which are responsible for filtering the blood and removing waste products. Injury to podocytes can lead to a disruption of the glomerular filtration barrier, which can result in proteinuria and hypoalbuminemia.

There are several underlying causes of podocyte injury, including immune-mediated glomerular injury, genetic mutations, and environmental factors such as infections, drugs, and toxins. In some cases, the underlying cause of nephrotic syndrome remains unknown, and this is referred to as idiopathic nephrotic syndrome.

In immune-mediated glomerular injury, the body’s immune system mistakenly attacks the podocytes, leading to their injury and dysfunction. This can occur due to a variety of mechanisms, including immune complex deposition, complement activation, and T-cell-mediated injury.

Genetic mutations can also play a role in the pathogenesis of nephrotic syndrome, particularly in cases of familial nephrotic syndrome. Mutations in genes that code for proteins involved in podocyte function, such as nephrin, podocin, and alpha-actinin-4, can result in podocyte dysfunction and injury.

Environmental factors such as infections, drugs, and toxins can also cause podocyte injury, leading to the development of nephrotic syndrome. Infections such as streptococcal infections and viral infections have been implicated in the development of nephrotic syndrome, as have drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) and certain antibiotics.

In summary, the pathogenesis of nephrotic syndrome is multifactorial and involves immune dysregulation, genetic predisposition, environmental factors, and podocyte injury. A better understanding of these underlying mechanisms is essential for the development of effective treatments for this condition.

 

Glomerulonephritis leading to Nephritic Syndrome

Glomerulonephritis (GN) is a group of kidney diseases characterized by inflammation of the glomeruli, which are the small filtering units in the kidney. GN can present as a nephritic syndrome, which is characterized by hematuria, proteinuria, hypertension, and renal impairment. The most common types of GN leading to nephritic syndrome are IgA nephropathy, post-infectious glomerulonephritis, and membranoproliferative glomerulonephritis.

• Etiology: IgA nephropathy is the most common form of GN worldwide, and its etiology is not fully understood, although it is thought to involve abnormal immune responses to antigens in the mucosal surfaces of the body, especially the gut. Post-infectious glomerulonephritis is caused by an immune response to an infection, most commonly streptococcal infection. Membranoproliferative glomerulonephritis is caused by deposition of immune complexes in the glomeruli, leading to inflammation.
• Pathogenesis: In IgA nephropathy, immune complexes containing IgA antibodies are deposited in the glomeruli, leading to inflammation and injury. In post-infectious glomerulonephritis, immune complexes containing antibodies to streptococcal antigens are deposited in the glomeruli, leading to inflammation and injury. In membranoproliferative glomerulonephritis, immune complexes containing antibodies and antigens are deposited in the glomeruli, leading to activation of the complement system and inflammation.
• Morphology: In IgA nephropathy, the glomeruli show mesangial expansion and proliferation with deposition of IgA and complement components. In post-infectious glomerulonephritis, the glomeruli show diffuse hypercellularity, with neutrophil infiltration and deposition of immune complexes. In membranoproliferative glomerulonephritis, the glomeruli show thickening of the glomerular basement membrane, mesangial expansion, and proliferation, with deposition of immune complexes and complement components.
• Clinical features: In IgA nephropathy, patients may present with recurrent episodes of macroscopic hematuria and mild proteinuria. In post-infectious glomerulonephritis, patients usually present with acute nephritis, with gross hematuria, edema, hypertension, and renal impairment. In membranoproliferative glomerulonephritis, patients may present with a nephrotic or nephritic syndrome, with proteinuria, hematuria, hypertension, and renal impairment.
• In summary, IgA nephropathy, post-infectious glomerulonephritis, and membranoproliferative glomerulonephritis are the most common types of GN leading to nephritic syndrome. Each of these conditions has a distinct etiology, pathogenesis, morphology, and clinical presentation, which helps in their diagnosis and management.

 

Some of the main causes of nephrotic syndrome include:

1. Minimal change disease: This is the most common cause of nephrotic syndrome in children. It occurs when the kidney’s filters become inflamed and leak protein into the urine.
2. Focal segmental glomerulosclerosis (FSGS): This condition occurs when scar tissue forms in the glomeruli, leading to protein leakage.
3. Membranous nephropathy: In this condition, the immune system attacks the glomeruli, causing them to become inflamed and leak protein.
4. Diabetes: High blood sugar levels can damage the blood vessels in the kidneys, leading to protein leakage and nephrotic syndrome.
5. Lupus nephritis: Lupus is an autoimmune disorder that can affect various parts of the body, including the kidneys. Lupus nephritis occurs when the immune system attacks the kidneys, leading to protein leakage.
6. Amyloidosis: This is a rare condition in which abnormal proteins called amyloids build up in the kidneys, causing damage and protein leakage.
7. Certain medications: Some medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), can cause nephrotic syndrome in rare cases.

It’s important to note that in some cases, the cause of nephrotic syndrome may be unknown (idiopathic).

 

Glomerulonephritis is a group of kidney disorders characterized by inflammation of the glomeruli, the filtering units of the kidneys. Nephrotic syndrome is a clinical syndrome that results from glomerular injury, causing proteinuria, hypoalbuminemia, edema, and hyperlipidemia. There are several types of glomerulonephritis that can lead to nephrotic syndrome, including minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy.

Etiology: The exact cause of most cases of glomerulonephritis leading to nephrotic syndrome is unknown, but several factors have been associated with their development, including immune-mediated mechanisms, infections, drugs, and systemic diseases. In some cases, genetic factors may also play a role.

Morphology: The morphology of glomerulonephritis varies depending on the underlying disease. In minimal change disease, the glomeruli appear normal under light microscopy, but electron microscopy reveals effacement of the podocyte foot processes. Focal segmental glomerulosclerosis is characterized by segmental scarring of the glomeruli, which may progress to global sclerosis. Membranous nephropathy is characterized by the thickening of the glomerular basement membrane, which can be seen on electron microscopy.

Pathogenesis: The pathogenesis of glomerulonephritis leading to nephrotic syndrome involves the activation of the immune system and the deposition of immune complexes in the glomeruli. In minimal change disease, the mechanism is unclear, but it is thought to involve the release of a circulating factor that damages the podocytes. Focal segmental glomerulosclerosis is thought to be caused by genetic mutations that affect the podocyte cytoskeleton, leading to foot process effacement and proteinuria. Membranous nephropathy is caused by the deposition of immune complexes containing autoantibodies against phospholipase A2 receptor (PLA2R) or thrombospondin type 1 domain-containing 7A (THSD7A) in the glomerular basement membrane.

Clinical Features: The clinical features of glomerulonephritis leading to nephrotic syndrome are similar regardless of the underlying disease. Patients typically present with edema, proteinuria, hypoalbuminemia, and hyperlipidemia. Edema may be generalized or localized to dependent areas, such as the legs and feet. Proteinuria may range from mild to severe and may be detected on urine dipstick testing or confirmed with 24-hour urine collection. Hypoalbuminemia results from the loss of protein in the urine and can lead to fluid accumulation in the tissues. Hyperlipidemia is a compensatory mechanism to maintain oncotic pressure and may be associated with the development of atherosclerosis. In some cases, patients may also experience hypertension, hematuria, and renal insufficiency.

In summary, glomerulonephritis leading to nephrotic syndrome is a group of kidney disorders that result from immune-mediated mechanisms, infections, drugs, and systemic diseases. The morphological changes vary depending on the underlying disease, but the pathogenesis involves the activation of the immune system and the deposition of immune complexes in the glomeruli. Clinical features include edema, proteinuria, hypoalbuminemia, and hyperlipidemia. Early detection and management are essential to prevent complications and improve outcomes