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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.
Bowman's capsule is a cup-like sac at the beginning of the tubular component of a nephron in the mammalian kidney that performs the first step in the filtration of blood to form urine. A glomerulus is enclosed in the sac. Fluids from blood in the glomerulus are collected in the Bowman's capsule.
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.
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.
Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people.
Minimal change disease (MCD), also known as lipoid nephrosis or nil disease, among others, is a disease affecting the kidneys which causes nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein to the urine (proteinuria), 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 presence in the urine due to protein loss. FSGS is a leading cause of excess protein loss—nephrotic syndrome—in children and adults in the US. Signs and symptoms include proteinuria and edema. Kidney failure is a common long-term complication of the disease. FSGS can be classified as primary, secondary, or genetic, depending on whether a particular toxic or pathologic stressor or genetic predisposition 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. An American epidemiological study 20 years ago demonstrated that FSGS is estimated to occur in 7 persons per million, with cisgender male African-Americans at higher risk.
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.
Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is a transmembrane protein that is a structural component of the slit diaphragm. It is present on the tips of the podocytes as an intricate mesh connecting adjacent foot processes. Nephrin contributes to the strong size selectivity of the slit diaphragm, however, the relative contribution of the slit diaphragm to exclusion of protein by the glomerulus is debated. The extracellular interactions, both homophilic and heterophilic—between nephrin and NEPH1—are not completely understood. In addition to eight immunoglobulin G–like motifs and a fibronectin type 3 repeat, nephrin has a single transmembrane domain and a short intracellular tail. Tyrosine phosphorylation at different sites on the intracellular tail contribute to the regulation of slit diaphragm formation during development and repair in pathology affecting podocytes. Podocin may interact with nephrin to guide it onto lipid rafts in podocytes, requiring the integrity of an arginine residue of nephrin at position 1160.
The glomerular basement membrane of the kidney is the basal lamina layer of the glomerulus. The glomerular endothelial cells, the glomerular 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. Glomerular basement membrane is secreted and maintained by podocyte cells.
Transient receptor potential cation channel, subfamily C, member 6 or Transient receptor potential canonical 6, also known as TRPC6, is a protein encoded in the human by the TRPC6 gene. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily.
Podocin is a protein that in humans is encoded by the NPHS2 gene.
CD2-associated protein is a protein that in humans is encoded by the CD2AP gene.
Protein MPV17 is a protein that in humans is encoded by the MPV17 gene. It is a mitochondrial inner membrane protein, which has a so far largely unknown role in mtDNA maintenance. Protein MPV17 is expressed in human pancreas, kidney, muscle, liver, lung, placenta, brain and heart. Human MPV17 is the orthologue of the mouse kidney disease gene, Mpv17. Loss of function has been shown to cause hepatocerebral mtDNA depletion syndromes (MDS) with oxidative phosphorylation failure and mtDNA depletion both in affected individuals and in Mpv17−/− mice.
Kin of IRRE-like protein 1, also known as NEPH1, is a protein that in humans is encoded by the KIRREL gene.
Glomerulopathy is a disease that impacts the glomeruli in the nephron, either inflammatory or noninflammatory. Glomerulopathy includes collapsing glomerulopathy, glomerulocystic kidney disease, glomerulomegaly, membranous nephropathy, and tip lesion glomerulopathy.
Glomerulonephrosis is a non-inflammatory disease of the kidney (nephrosis) presenting primarily in the glomerulus as nephrotic syndrome. The nephron is the functional unit of the kidney and it contains the glomerulus, which acts as a filter for blood to retain proteins and blood lipids. Damage to these filtration units results in important blood contents being released as waste in urine. This disease can be characterized by symptoms such as fatigue, swelling, and foamy urine, and can lead to chronic kidney disease and ultimately end-stage renal disease, as well as cardiovascular diseases. Glomerulonephrosis can present as either primary glomerulonephrosis or secondary glomerulonephrosis.
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.
References
- ↑ Jarad G, Miner JH (May 2009). "Update on the glomerular filtration barrier". Current Opinion in Nephrology and Hypertension. 18 (3): 226–32. doi:10.1097/mnh.0b013e3283296044. PMC 2895306 . PMID 19374010.
- ↑ Mollet G, Ratelade J, Boyer O, Muda AO, Morisset L, Lavin TA, Kitzis D, Dallman MJ, Bugeon L, Hubner N, Gubler MC, Antignac C, Esquivel EL (October 2009). "Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome". Journal of the American Society of Nephrology. 20 (10): 2181–9. doi:10.1681/ASN.2009040379. PMC 2754108 . PMID 19713307.
- ↑ Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Emma F, Goldstein SL (2016). Pediatric Nephrology. Springer. ISBN 9783662435960. OCLC 1050008865.
- 1 2 Tabassum A, Rajeshwari T, Soni N, Raju DS, Yadav M, Nayarisseri A, Jahan P (March 2014). "Structural characterization and mutational assessment of podocin - a novel drug target to nephrotic syndrome - an in silico approach". Interdisciplinary Sciences, Computational Life Sciences. 6 (1): 32–9. doi:10.1007/s12539-014-0190-4. PMID 24464702. S2CID 17163784.
- ↑ Saleem MA, Ni L, Witherden I, Tryggvason K, Ruotsalainen V, Mundel P, Mathieson PW (October 2002). "Co-localization of nephrin, podocin, and the actin cytoskeleton: evidence for a role in podocyte foot process formation". Am J Pathol. 161 (4): 1459–66. doi:10.1016/S0002-9440(10)64421-5. PMC 1867300 . PMID 12368218.