Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy. Severe proteinuria can cause nephrotic syndrome in which there is worsening swelling of the body.
Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy urine. Complications may include blood clots, infections, and high blood pressure.
The glomerulus is a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally supported by the mesangium, composed of intraglomerular mesangial cells. The blood is filtered across the capillary walls of this tuft through the glomerular filtration barrier, which yields its filtrate of water and soluble substances to a cup-like sac known as Bowman's capsule. The filtrate then enters the renal tubule of the nephron.
Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule filters the blood, retaining large molecules such as proteins while smaller molecules such as water, salts, and sugars are filtered as the first step in the formation of urine. Although various viscera have epithelial layers, the name visceral epithelial cells usually refers specifically to podocytes, which are specialized epithelial cells that reside in the visceral layer of the capsule. One type of specialized epithelial cell is podocalyxin.
Glomerulonephritis (GN) is a term used to refer to several kidney diseases. Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.
Minimal change disease is a disease affecting the kidneys which causes a nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein in the urine, which causes the widespread edema and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 6 years of age. MCD is responsible for 10–25% of nephrotic syndrome cases in adults. It is also the most common cause of nephrotic syndrome of unclear cause (idiopathic) in children.
Focal segmental glomerulosclerosis (FSGS) is a histopathologic finding of scarring (sclerosis) of glomeruli and damage to renal podocytes. This process damages the filtration function of the kidney, resulting in protein loss in the urine. FSGS is a leading cause of excess protein loss—nephrotic syndrome—in children and adults. Signs and symptoms include proteinuria, water retention, and edema. Kidney failure is a common long-term complication of disease. FSGS can be classified as primary versus secondary depending on whether a particular toxic or pathologic stressor can be identified as the cause. Diagnosis is established by renal biopsy, and treatment consists of glucocorticoids and other immune-modulatory drugs. Response to therapy is variable, with a significant portion of patients progressing to end-stage kidney failure. FSGS is estimated to occur in 2-3 persons per million, with males and African peoples at higher risk.
Galloway Mowat syndrome is a very rare autosomal recessive genetic disorder, consisting of a variety of features including hiatal hernia, microcephaly and nephrotic syndrome.
Congenital nephrotic syndrome is a rare kidney disease which manifests in infants during the first 3 months of life, and is characterized by high levels of protein in the urine (proteinuria), low levels of protein in the blood, and swelling. This disease is primarily caused by genetic mutations which result in damage to components of the glomerular filtration barrier and allow for leakage of plasma proteins into the urinary space.
The glomerular basement membrane of the kidney is the basal lamina layer of the glomerulus. The glomerular endothelial cells, the glomeular basement membrane, and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that forms in Bowman's capsule. The glomerular basement membrane is a fusion of the endothelial cell and podocyte basal laminas, and is the main site of restriction of water flow. Glomeular basement membrane is secreted and maintained by podocyte cells.
Podocin is a protein component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus. Mutations in the podocin gene NPHS2 can cause nephrotic syndrome, such as focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Symptoms may develop in the first few months of life or later in childhood.
Podocin is a protein that in humans is encoded by the NPHS2 gene.
Collagen alpha-4(IV) chain is a protein that in humans is encoded by the COL4A4 gene.
Cadherin-3, also known as P-Cadherin, is a protein that in humans is encoded by the CDH3 gene.
CD2-associated protein is a protein that in humans is encoded by the CD2AP gene.
Synaptopodin is a protein that in humans is encoded by the SYNPO gene.
Kin of IRRE-like protein 1, also known as NEPH1, is a protein that in humans is encoded by the KIRREL gene.
Effacement is the shortening, or thinning, of a tissue.
Dendrin is a neural and renal protein whose exact function is still relatively unclear; however, its location in the brain and kidneys is well known as are some of the neural processes it affects. Within the brain, dendrin can be found in neurons and is most notably associated with sleep deprivation. Sleep deprivation causes some areas of the brain dendrin levels to increase, but this increase is insignificant and in total sleep deprivation causes a decrease of the mRNA and protein form of dendrin. Along with two other proteins, MAGI/S-SCAM and α-actinin, dendrin is linked to synaptic plasticity and memory formation in the brain. Nicotine levels have also been shown to have an effect on dendrin expression in the brain. Although unlike sleep deprivation, nicotine increases overall dendrin level. Originally thought to be a brain specific protein, there is now evidence to suggest that dendrin is also found in the kidneys. Dendrin is used to detect glomerulopathy or renal disease, based on its location in the kidneys. Within the kidneys it also works to prevent urinary protein loss. Most studies and information on dendrin pertain specifically to rat or mice brains.
Karl Tryggvason is an Icelandic medical researcher.
