Glomerulonephritis (Acute and Chronic Kidney Glomerular Disease)

The glomerulus is the communication point between the bloodstream and nephron, the functional unit of the kidney. It is composed of the glomerular capillaries and Bowman’s capsule of the nephron. Fluid from the blood in the glomerular capillaries pass into the Bowman’s capsule and then enters the tubules where it is processed to form urine.  The glomerular capillaries congregate as tufts within the Bowman’s capsule. Fluid has to pass through the endothelial cells of the capillaries, and the closely associated visceral membrane of the Bowman’s capsule which is separated from the capillary wall by the basement membrane, then through the parietal membrane of the Bowman’s capsule to enter the nephron.  Mesangial cells among the glomerular capillaries regulate the blood flow in the capillaries. If these cells and layers of the glomerulus are damaged, glomerular filtration and therefore normal kidney functioning is impaired.

What is glomerulonephritis?

Glomerulonephritis literally means inflammation of the glomerulus but includes a number of disorders that affect the structure and function of the glomerulus without any prominent inflammation. It is therefore also referred to as glomerular disease or glomerulopathy. In glomerulonephritis, various known and unknown causes trigger immune activity against the glomeruli which damages it.

The glomerulus is the head of the nephron which is responsible for filtering fluid from the blood. This fluid is later processed in the tubule (the rest of the nephron) until urine is eventually formed. Each kidney has about 1 million nephrons that act together to complete the various functions including removing waste substances from the blood, regulating blood volume and blood pressure. If a significant number of nephrons are damaged, these functions will be significantly hampered.

The kidney is constantly losing nephrons with age. This is a slow process and only commences after the age of 40 years. For every decade of life thereafter, the kidney loses about 10% of its functioning nephrons. Since the progression is so gradual, the remaining healthy nephrons are able to compensate without any significant impairment of normal kidney functioning. In glomerulonephritis, however, there is a  more rapid and extensive damage of the nephrons.

Pathophysiology of Glomerulonephritis

How does glomerulonephritis occur?

Glomerulonephritis is known to be an immune reaction mediated by antigen-antibody complexes.  An antigen is the trigger substance against which antibodies are formed by the immune system. The antibodies then bind with the antigen and this antigen-antibody complex can instigate a number of immune activities designed to protect the body. In the process, inflammation arises in whichever tissue that the targeted immune response is occurring. Although the exact cause of glomerulonephritis is not always understood, the mechanism by which it occurs is proposed in two different models – immune complex deposition and circulating immune complexes. Other mechanisms may involve cell-mediated injury or cytotoxic antibodies.

In immune complex deposition, it is believed that antibodies are directed against antigens that are “planted” in the glomerulus or against antigens that are normal components of the glomerulus, specifically the glomerular basement membrane (GBM). The immune activity is therefore specifically targeted at the glomerulus.

With circulating immune complexes, the antigen-antibody complexes are circulating in the bloodstream and eventually reach the glomerulus during glomerular filtration. These complexes form in the backdrop of several autoimmune or infectious diseases and the antigen may be endogenous (created within the body) or exogenous (from foreign matter or microogranisms) in nature. In these cases, immune activity is targeted at the circulating immune complex and can lead to inflammation at other sites in the body as well as the glomerulus.

In response to the inflammation, different histologic alterations may be seen in the glomerulus. This includes :

• Increase in the number of cells (capillary endothelium or mesangial cells)
• Thickening of the basement membrane
• Tissue degeneration – hyalinosis and sclerosis

Types of Glomerulonephritis

Primary and Secondary Glomerulonephritis

Glomerulonephritis may be primary or secondary. Primary glomerulonephritis arises on its own without any other underlying disease. Secondary glomerulonephritis occurs as a consequence of some other disease, which may not even involve the kidney.

Acute and Chronic Glomerulonephritis

Furthermore glomerulonephritis can be classified as acute or chronic. In acute glomerulonephritis, the condition starts suddenly and the tissue damage progresses rapidly. With chronic glomerulonephritis, the condition develops gradually and damage becomes extensive after months or years.

Different Types of Glomerulonephritis

There are several different types of glomerulonephritis based on the various distinct histological patterns that arise with glomerular inflammation. Some of the more common types of glomerulonephritis includes :

• Minimal change nephropathy
• Primary focal segmental glomerulosclerosis (FSGS)
• Membranous nephropathy
• Membranoproliferative glomerulonephritis (also called mesangiocapillary)
• IgA nephropathy
• Post-infectious glomerulonephritis which is a sub-type of acute proliferative glomerulonephritis
• Crescentic glomerulonephritis

Apart from the differences in the pattern and severity of tissue damage in each type of glomerulonephritis, it may also differ  in the way kidney functioning is impaired and arise with different causes.

Causes of Glomerulonephritis

The is a wide range of causes of glomerulonephritis. Some may solely involve the kidney while others are due to systemic disease which affect a number of organs simultaneously. Sometimes the cause of glomerulonephritis is unknown – idiopathic. The causes of glomerulonephritis may include :

• Infections – post-streptococcal, subacute bacterial endocarditis, viral infections, parasitic infections like malaria and less commonly fungal infections.
• Autoimmune diseases – systemic lupus erythematosus (SLE), Goodpasture’s syndrome, vasculitis (Wegener granulomatosis and polyarteritis nodosa), Henoch-Schönlein purpura.
• Immune-mediated hypersensitivity (atopy) particularly in children.
• Medication like those drugs used in the treatment of SLE and hemolytic-uremic syndrome.
• Diabetes mellitus
• Malignant hypertension (high blood pressure)
• Amyloidosis
• Inherited diseases like Alport’s syndrome.
• Hodgkin’s lymphoma (mainly in adults).

Signs and Symptoms of Glomerulonephritis

The clinical features may vary between acute and chronic glomerulonephritis and even among the different histological types. In chronic glomerulonephritis specifically, the patient may be asymptomatic (no symptoms) for long periods of time. The sign and symptoms of glomerulonephritis includes :

• Hematuria (blood in the urine) which may appear as pink-colored or brownish urine.
• Proteinuria (protein in the urine) which may present as foamy urine (frothy).
• Edema (swelling) most prominent in the face, hands, abdomen and feet.
• Hypertension (high blood pressure)
• Azotemia (high urea levels in the blood) which leads to various additional signs and symptoms (uremia).

Glomerulonephritis may lead to a collection of clinical features grouped together as glomerular syndromes and includes :

• Nephrotic syndrome – proteinuria (protein in urine), hypoalbuminema (low blood proteins), edema (swelling due to fluid retention), hyperlipidemia (high blood lipids), lipiduria (lipids in the urine).
• Nephritic syndrome – hematuria (blood in urine), azotemia (high urea levels in blood), proteinuria, oliguria (large volume of urine), edema, and hypertension (high blood pressure).
• Rapidly progressing glomerulonephritis – nephritis (kidney inflammation), proteinuria, and acute renal failure.

Additional signs and symptoms of glomerulonephritis may include :

• Anemia
• Fatigue
• Nausea and vomiting
• Paleness and/or yellowing of the skin
• Itching of the skin
• Dehydration