“Focal segmental glomerulosclerosis”的意思、由来-开放百科全书

词条

Focal segmental glomerulosclerosis

释义

Classification
Pathologic variants
Causes
Genetic causes
Diagnosis
Symptoms and signs Tests Differential diagnosis
Treatment
Etymology
Notable patients
See also
References
Further reading
External links

{{Infobox medical condition (new)
| name = Focal segmental glomerulosclerosis
| image = Focal segmental glomerulosclerosis - high mag.jpg
| caption = Light micrograph of focal segmental glomerulosclerosis, hilar variant. Kidney biopsy. PAS stain.
|
| pronounce =
| field =
| synonyms =
| symptoms =
| complications =
| onset =
| duration =
| types =
| causes =
| risks =
| diagnosis =
| differential =
| prevention =
| treatment =
| medication =
| prognosis =
| frequency =
| deaths =
}}

Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome in children and adolescents, as well as a leading cause of kidney failure in adults.^[1] It is also known as "focal glomerular sclerosis" or "focal nodular glomerulosclerosis."^[2] It accounts for about a sixth of the cases of nephrotic syndrome.^[3] (Minimal change disease (MCD) is by far the most common cause of nephrotic syndrome in children: MCD and primary FSGS may have a similar cause.^[1])

Classification

Depending on the cause it is broadly classified as:

Primary, when no underlying cause is found; usually presents as nephrotic syndrome
Secondary, when an underlying cause is identified; usually presents with kidney failure and proteinuria. This is actually a heterogeneous group including numerous causes such as
- Toxins and drugs such as heroin and pamidronate
- Familial forms
- Secondary to nephron loss and hyperfiltration, such as with chronic pyelonephritis and reflux, morbid obesity, diabetes mellitus

There are many other classification schemes also.

Pathologic variants

Five mutually exclusive variants of focal segmental glomerulosclerosis may be distinguished by the pathologic findings seen on renal biopsy:^[4]

Collapsing variant
Glomerular tip lesion variant
Cellular variant
Perihilar variant
Not otherwise specified (NOS) variant.

Recognition of these variants may have prognostic value in individuals with primary focal segmental glomerulosclerosis (i.e. where no underlying cause is identified). The collapsing variant is associated with higher rate of progression to end-stage renal disease, whereas glomerular tip lesion variant has a low rate of progression to end-stage renal disease in most patients. Cellular variant shows similar clinical presentation to collapsing and glomerular tip variant but has intermediate outcomes between these two variants. However, because collapsing and glomerular tip variant show overlapping pathologic features with cellular variant, this intermediate difference in clinical outcomes may reflect a sampling bias in cases of cellular focal segmental glomerulosclerosis (i.e. unsampled collapsing variant or glomerular tip variant). The prognostic significance of perihilar and NOS variants has not yet been determined. The NOS variant is the most common subtype. Collapsing variant is the most common type of glomerulopathy caused by HIV infection.

Causes

Some general secondary causes are listed below:

Glomerular hypertrophy/hyperfiltration
- Unilateral renal agenesis
- Morbid obesity
Scarring due to previous injury
- Focal proliferative glomerulonephritis
- Vasculitis
- Lupus
Toxins (pamidronate)
Human immunodeficiency virus-associated nephropathy
Heroin nephropathy^[5]

Focal segmental glomerulosclerosis may develop following acquired loss of nephrons from reflux nephropathy. Proteinuria is nonselective in most cases and may be in subnephrotic range (nephritic range <3.0gm/24hr) or nephritic range.^[6]

Genetic causes

There are currently several known genetic causes of the hereditary forms of FSGS.

Gene	OMIM	Description
FSGS1: ACTN4	603278}}	The first gene involved with this disorder is ACTN4, which encodes alpha-actinin 4. This protein crosslinks bundles of actin filaments and is present in the podocyte. Mutations in this protein associated with FSGS result in increased affinity for actin binding, formation of intracellular aggregates, and decreased protein half-life. While it is unclear how these effects might lead to FSGS there are a number of theories. Firstly, protein aggregation may have a toxic effect on the podocyte. Secondly, decreased protein half-life or increased affinity for actin binding may alter actin polymerization and thereby affect the podocytes cytoskeletal architecture.^[7]
FSGS2: TRPC6	603965}}	A second gene associated with FSGS is TRPC6, which encodes a member of the canonical family of TRP channels. This family of ion channels conduct cations in a largely non-selective manner. As with ACTN4, TRPC6 is expressed in podocytes. While TRP channels can be activated through a variety of methods, TRPC6 is known to be activated by phospholipase C stimulation. There are at least 6 mutations in this channel, located throughout the channel. At least one of these mutations, P112Q, leads to increased intracellular calcium influx. It is unclear how this might lead to FSGS, though it has been proposed that it may result in alteration of podocyte dynamics or podocytopenia.^[7]
FSGS3: CD2AP	607832}}	Another gene that may be involved in hereditary forms of FSGS is the gene known as CD2AP (CD2 associated protein) or CMS (Cas binding protein with multiple SH3 domains). The protein expressed by this gene is expressed in podocytes where it interacts with fyn and synaptopodin. There is a report that a splicing mutation in this gene was found in two patients with HIV associated FSGS and this led to altered protein translation. This has been theorized to result in altered actin binding and, thus, alteration of the cytoskeletal podocyte architecture.^[7]
FSGS4: APOL1	612551}}	In people of African descent, two common variants in APOL1 have been associated with FSGS. It is believed that these variants arose as a defensive mechanism against Trypanosoma brucei rhodesiense or some other sub-Saharan parasite despite conferring high susceptibility to FSGS when inherited from both parents.^[8]
FSGS5: INF2	613237}}	Another gene associated with FSGS is INF2, which encodes a member of the formin family of actin-regulating proteins. The observation that alterations in this podocyte-expressed formin cause FSGS emphasizes the importance of fine regulation of actin polymerization in podocyte function.^[9]
SRN1: NPHS2	600995}}	Mutations in the NPHS2 gene, which codes for the protein called podocin,^[10] can cause focal segmental glomerulosclerosis.^[11] This is a recessive form of FSGS.^[12] An affected individual has two mutant copies of the NPHS2 gene, in contrast to ACTN4 and TRPC6 mediated forms of disease, which are dominant and require only one mutant copy of the gene. NPHS2-mediated FSGS is resistant to treatment with steroids.

Some researchers found SuPAR as a cause of FSGS.{{Citation needed|date=May 2014}}

Another gene that has been associated with this syndrome is the COL4A5 gene.^[13]

Diagnosis

Symptoms and signs

In children and some adults, FSGS presents as a nephrotic syndrome, which is characterized by edema (associated with weight gain), hypoalbuminemia (low serum albumin, a protein in the blood), hyperlipidemia and hypertension (high blood pressure). In adults, it may also present as kidney failure and proteinuria, without a full-blown nephrotic syndrome.

Tests

Urinalysis
Blood tests — cholesterol
Kidney biopsy

Differential diagnosis

Minimal change disease, especially in children
Membranous glomerulonephritis
Several other

Treatment

Etymology

The individual components of the name refer to the appearance of the kidney tissue on biopsy: focal—only some of the glomeruli are involved (as opposed to diffuse), segmental—only part of each glomerulus is involved (as opposed to global),^[14] glomerulosclerosis—refers to scarring of the glomerulus (a part of the nephron (the functional unit of the kidney)). The glomerulosclerosis is usually indicated by heavy PAS staining and findings of immunoglobulin M (IgM) and C3-convertase (C3) in the sclerotic segment.^[15]

Notable patients

Former NBA basketball players Sean Elliott and Alonzo Mourning have both survived bouts with FSGS. Mourning is an Ambassador to the NephCure Foundation. Pro bodybuilder Flex Wheeler was diagnosed with FSGS and had a kidney transplant. Former MLS player Clyde Simms retired from professional soccer in 2014 due to FSGS.^[16]
Gary Coleman American actor, known for his childhood role as Arnold Jackson in the American sitcom Diff'rent Strokes.
Andy Cole, former Newcastle Utd, Manchester United and England international football player^[17]
Ed Hearn, former Major League Baseball player for the New York Mets and Kansas City Royals
Aries Merritt, 110 metres hurdles world record holder and 2012 Olympic champion, had a kidney transplant for collapsing FSGS days after coming third in the 2015 World Championships.^[18]
Natalie Cole, American singer^[19]

References

{Mujtaba, 2015 #31}

External links

{{Medical resources
| ICD10 = {{ICD10|N|00||n|00}}-{{ICD10|N|08||n|00}} (with .1 suffix)
| ICD9 = {{ICD9|581.1}}
| OMIM = 603278
| OMIM_mult = {{OMIM2|603965}} {{OMIM2|607832}} {{OMIM2|612551}} {{OMIM2|613237}} {{OMIM2|600995}}
| MedlinePlus =000478
| eMedicineSubj = med
| eMedicineTopic = 2944
| MeshID = D005923
}}{{Nephrology}}{{Channelopathy}}{{DEFAULTSORT:Focal Segmental Glomerulosclerosis}}

3 : Kidney diseases|Channelopathies|Disorders causing edema

随便看

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。