Fundamentals
Nephritis and glomerulonephritis
- Nephritis describes damage to the kidneys due to inflammation.
- Glomerulonephritis describes nephritis involving the glomerulus.
Ultrafiltration
Ultrafiltration occurs at the glomerulus. Liquid and small molecules need to pass through 3 layers to enter the nephron tubules:
- The capillary endothelium:
- Allows fluid, plasma proteins, and large substances through
- Does not allow red or white blood cells and some proteins through
- The glomerular basement membrane:
- Allows fluid and solutes through
- Does not allow intermediate-large substances including some proteins through
- The epithelium of the Bowman’s capsule (made of podocytes):
- Allows fluid and small solutes through
- Does not allow large molecules such as proteins through
These three layers filter the blood with each layer preventing increasingly large substances from passing through into the nephron tubule. Overall, cells (such as red blood cells or white blood cells) and large proteins are not passed through.
Nephritic vs. nephrotic syndrome
A syndrome is a set of signs and symptoms correlated with each other and associated with a particular disease or disorder.
Nephrotic and nephritic syndrome affect different parts of the glomerulus which leads to different clinical pictures and hence, their classifications:
- Nephritic syndrome describes the signs and symptoms generally seen due to dysfunction of the capillary endothelium. This usually refers to severe and acute presentations of glomerulonephritis.
- Nephrotic syndrome describes the signs and symptoms generally seen due to the dysfunction of podocytes. It is less associated with inflammation.
This distinction is important as it helps categorise glomerular diseases and guides their management. It is important to note that diseases can overlap and have features of both, or have features that do not fit the definition of either.
Nephritic Syndrome
Overview
Inflammation leads to damage to the capillary endothelium. As mentioned above, this layer prevents the leakage of red blood and white blood cells into the nephron tubules. Nephritic syndrome is defined as:
- Proteinuria
- Haematuria
- Hypertension
- Oliguria
Haematuria and proteinuria
Therefore, this can lead to haematuria (red blood cells present in the urine), and pyuria (white blood cells in the urine). Since cells are relatively large and now let through, protein can also be let through, however, this is much less than in nephrotic syndrome.
Hypertension
Glomerular damage due to inflammation can lead to reduced filtration and oliguria. This can be due to immune complex deposition impeding effective filtration. This lack of filtration can lead to hypertension as more salt and water is retained.
Nephrotic Syndrome
Overview
Damage and dysfunction of the podocytes can lead to a loss of protein in the urine. As mentioned above, the podocytes are the ‘last line’ of filtration where large molecules such as proteins are prevented from entering the nephron tubule. Nephrotic syndrome is defined as:
- Proteinuria (>3.5 g/24hr)
- Hypoalbuminaemia
- Oedema
Other features that may also be seen include:
- Hyperlipidaemia
- Hypercoagulability
- Immunodeficiency
Proteinuria
Damage to the podocytes, therefore, leads to proteinuria. In contrast to the amount of protein lost in nephritic syndrome, a large amount of protein is lost in nephrotic syndrome (over 3.5 g/24hr). Proteinuria can lead to frothy urine and the proteins lost include albumin, antithrombin III, and immunoglobulins.
Hypoalbuminaemia
Albumin is also lost from the urine, and the liver cannot produce enough to compensate. This leads to hypoalbuminaemia. Hypoalbuminaemia reduces the oncotic pressure of the serum, leading to sodium and water retention, and this leads to oedema, which can manifest over the eyes (periorbital oedema) or the legs and peripheries.
Hyperlipidaemia
The loss of protein in the urine stimulates protein synthesis in the liver, leading to an overproduction of lipoproteins. Enzymes involved in lipid catabolism are also lost in the urine. These two effects lead to hyperlipidaemia.
Hypercoagulability
Antithrombin III is another protein that is lost in the urine. It inactivates different elements of the coagulation cascade. Therefore, a loss of antithrombin III leads to hypercoagulability and an increased risk of venous thromboembolism (e.g. deep vein thrombosis or pulmonary embolism).
Immunodeficiency
This may occur due to the loss of immunoglobulins in the urine.
Causes of Nephritic and Nephrotic Syndrome
Mainly Nephritic Causes
Causes that are mainly nephritic often lead to rapidly progressive glomerulonephritis (RPG) can be divided into:
- Antibody-mediated diseases (type II hypersensitivity, type I RPG):
- Immune complex diseases (type III hypersensitivity, type II RPG):
- IgA nephropathy
- Post-streptococcal glomerulonephritis
- Lupus nephritis
- Pauci-immune – no immune complexes or anti-glomerular basement membrane antibodies, usually associated with vasculitides (type III RPG):
- Granulomatosis with polyangiitis
- Eosinophilic granulomatosis with polyangiitis
- Microscopic polyangiitis
Mainly Nephrotic Causes
Causes that are mainly nephrotic can be divided into:
- Non-proliferative causes (numbers of cells in the glomerulus are unchanged):
- Minimal Change Disease
- Focal Segmental Glomerulonephritis
- Membranous glomerulonephritis
- Proliferative causes (numbers of cells in the glomerulus are increased)
- Membranoproliferative glomerulonephritis
- Other:
