focal segmental glomerulosclerosis

巣状分節性糸球体硬化症 FSGS

WordNet

1. divide or split up; "The cells segmented"
2. one of the parts into which something naturally divides; "a segment of an orange"
3. divide into segments; "segment an orange"; "segment a compound word" (同)section
4. of or relating to a focus; "focal length"
5. having or localized centrally at a focus; "focal point"; "focal infection"
6. divided or organized into speech segments or isolable speech sounds

PrepTutorEJDIC

1. 区分,部分 / 切片(円などの一部);(直線の)線分 / …‘を'分ける / 分かれている,分裂する
2. 焦点の

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/23 11:54:17」(JST)

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Focal segmental glomerulosclerosis
Classification and external resources
Light micrograph of focal segmental glomerulosclerosis, hilar variant. Kidney biopsy. PAS stain.
ICD-10	N00-N08 (with .1 suffix)
ICD-9	581.1
OMIM	603278 603965 607832 612551 613237 600995
MedlinePlus	000478
eMedicine	med/2944
MeSH	D005923

Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome in children and adolescents, as well as an important cause of kidney failure in adults. It is also known as "focal glomerular sclerosis" or "focal nodular glomerulosclerosis." It accounts for about a sixth of the cases of nephrotic syndrome. (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.)

Appearance

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), 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 IgM and C3 in sclerotic segment.

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
  • Infections such as HIV (known as HIV-Associated Nephropathy)
  • 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

Micrograph of the collapsing variant of FSGS (collapsing glomerulopathy). A collapsed glomerulus is seen at the top, right-of-centre. PAS stain. Kidney biopsy.

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

1. Collapsing variant
2. Glomerular tip lesion variant
3. Cellular variant
4. Perihilar variant
5. 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 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 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.

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.
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.
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.
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.
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.
SRN1: NPHS2	600995	Mutations in the NPHS2 gene, which codes for the protein called podocin, can cause focal segmental glomerulosclerosis. This is a recessive form of FSGS. 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.

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. Some researchers found SuPAR as cause of FSGS.

Tests

• Urinalysis
• Blood tests – cholesterol
• Kidney biopsy

Differential diagnosis

• Minimal change disease, especially in children
• Several others

Treatment

• Salt restriction and diuretics, such as furosemide, for edema
• Antihypertensives (especially ACEIs) – if the blood pressure is too high
• treat present hyperlipidemia (e.g. statins, fibrates; although fibrates are contraindicated in renal failure)
• Aldosterone antagonist to decrease proteinuria and thus offer a degree of reno-protection
• Angiotensin II receptor antagonist
• Corticosteroids, such as prednisone – based on the clinical judgment of physician (no broad consensus/guideline)^{[citation needed]}
• Cytotoxics, such as cyclophosphamide may be used to induce remission in patients presenting with FSGS refractory to corticosteroids, or in patients who do not tolerate steroids.
• Plasmapheresis – blood cleansing using a machine to remove the patient's blood plasma and replacing it with donor plasma.
• Vitamin E
• Fish oil
• Immunosuppressive drugs
• None – sometimes none of the above works and the patient will require dialysis with possibly later transplantation of a new kidney.^{[citation needed]}

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.

See also

• Glomerulonephritis

References

External links

• Cause for FSGS discovered by nephcure (Published online 31 July 2011 on nature {http://www.nature.com/nm/journal/v17/n8/abs/nm.2411.html})
• NephCure Foundation Only organization solely committed to support research seeking the cause of Nephrotic Syndrome and FSGS, improve treatment and find the cure.
• Kidcomm An online resource for parents dealing with childhood kidney diseases (FSGS, Nephrotic Syndrome and others)
• FSGS Research A team of kidney doctors and scientists from Brigham and Women's Hospital / Harvard Medical School working to learn more about the cause of FSGS and Nephrotic Syndrome in children and adults, with an emphasis on the genetic basis of these diseases.
• A general overview of Renal Pathology
• Tahzib M, Frank R, Gauthier B, Valderrama E, Trachtman H (October 1999). "Vitamin E treatment of focal segmental glomerulosclerosis: results of an open-label study". Pediatr. Nephrol. 13 (8): 649–52. doi:10.1007/s004670050674. PMID 10502120. 

UpToDate Contents

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• 1. 原発性巣状分節性糸球体硬化症の治療 treatment of primary focal segmental glomerulosclerosis
• 2. 巣状分節性糸球体硬化症の疫学、分類、および病因 epidemiology classification and pathogenesis of focal segmental glomerulosclerosis
• 3. 移植腎における巣状分節性糸球体硬化症 focal segmental glomerulosclerosis in the transplanted kidney
• 4. HIV感染に関連しない巣状分節性糸球体硬化症 collapsing focal segmental glomerulosclerosis not associated with hiv infection
• 5. HIV関連腎症（HIVAN） hiv associated nephropathy hivan

English Journal

• Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis.

• Kumar J, Shatat IF, Skversky AL, Woroniecki RP, Del Rio M, Perelstein EM, Johnson VL, Mahesh S.SourceWeill Cornell Medical College, Helmsley Towers 3, Box 176, New York, NY, 10021, USA, juk2013@med.cornell.edu.
• Pediatric nephrology (Berlin, Germany).Pediatr Nephrol.2013 Feb;28(2):333-8. doi: 10.1007/s00467-012-2314-6. Epub 2012 Oct 4.
• BACKGROUND: Focal segmental glomerulosclerosis (FSGS) recurs in 20-40 % of allografts. Plasmapheresis (TPE) has been one of the mainstays of treatment with variable results. Rituximab (RTX), a monoclonal antibody to the protein CD20, is being used for treatment of recurrent FSGS (recFSGS) but pedia
• PMID 23052653

• Novel INF2 mutation p. L77P in a family with glomerulopathy and Charcot-Marie-Tooth neuropathy.

• Rodriguez PQ, Lohkamp B, Celsi G, Mache CJ, Auer-Grumbach M, Wernerson A, Hamajima N, Tryggvason K, Patrakka J.SourceDivision of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.
• Pediatric nephrology (Berlin, Germany).Pediatr Nephrol.2013 Feb;28(2):339-43. doi: 10.1007/s00467-012-2299-1. Epub 2012 Sep 11.
• BACKGROUND: Mutations in inverted formin, FH2, and WH2 domain containing (INF2) are common causes of dominant focal segmental glomerulosclerosis. INF2 encodes a member of the diaphanous-related formin family, which regulates actin and microtubule cytoskeletons. Charcot-Marie-Tooth neuropathy (CMT) i
• PMID 22961558

• Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach.

• Gadegbeku CA, Gipson DS, Holzman LB, Ojo AO, Song PX, Barisoni L, Sampson MG, Kopp JB, Lemley KV, Nelson PJ, Lienczewski CC, Adler SG, Appel GB, Cattran DC, Choi MJ, Contreras G, Dell KM, Fervenza FC, Gibson KL, Greenbaum LA, Hernandez JD, Hewitt SM, Hingorani SR, Hladunewich M, Hogan MC, Hogan SL, Kaskel FJ, Lieske JC, Meyers KE, Nachman PH, Nast CC, Neu AM, Reich HN, Sedor JR, Sethna CB, Trachtman H, Tuttle KR, Zhdanova O, Zilleruelo GE, Kretzler M.SourceDepartment of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
• Kidney international.Kidney Int.2013 Jan 16. doi: 10.1038/ki.2012.428. [Epub ahead of print]
• The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary study program, a training prog
• PMID 23325076

Japanese Journal

• A case of minimal change nephrotic syndrome with immunoglobulin A nephropathy transitioned to focal segmental glomerulosclerosis

• Hirose Misaki,Nishino Tomoya,Uramatsu Tadashi,Obata Yoko,Kitamura Mineaki,Kawazu Tayo,Miyazaki Masanobu,Taguchi Takashi,Kohno Shigeru
• Clinical and Experimental Nephrology 16(3), 473-479, 2012-06
• … Light microscopy revealed focal sclerotic lesions of the glomeruli, and an immunofluorescence study revealed attenuation of mesangial IgA and C3 deposition. … These findings led to the diagnosis that minimal change nephrotic syndrome had transitioned to focal segmental glomerulosclerosis, whereby mesangial IgA deposition was reduced by immunosuppressive treatment. …
• NAID 120003850312

• 症例 HIV関連腎症によりネフローゼ症候群と急速な腎機能低下をきたした1例

• 木村 友則,安田 圭子,小尾 佳嗣 [他]
• The Japanese journal of nephrology 54(2), 94-98, 2012
• NAID 40019255608

Related Links

• Focal segmental glomerulosclerosis - Wikipedia, the free encyclopedia

Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome in children and adolescents, as well as an important cause of kidney failure in adults. It is also known as "focal glomerular sclerosis" or "focal nodular ...

• Focal Segmental Glomerulosclerosis (FSGS) - UNC Kidney Center

FSGS stands for Focal Segmental Glomerulosclerosis. It is a relatively common form of kidney disease, especially in the US. Although there are several known risk factors, we don't yet know why most people develop FSGS. In order to be ...

Related Pictures

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★リンクテーブル★

リンク元	「巣状分節性糸球体硬化症」「FSGS」「focal sclerosing glomerulonephritis」
関連記事	「focal」「segmental」「segment」

「巣状分節性糸球体硬化症」

　　[★]

英

focal segmental glomerulosclerosis, FSGS, focal and segmental glomerulosclerosis

同

巣状硬化性糸球体腎炎 focal sclerosing glomerulonephritis

関

巣状糸球体硬化症 focal glomerulosclerosis, FGS

概念

• 本症は糸球体が巣状かつ分節状に硬化した疾患。
• ネフローゼの20-30%を占める

症状

• 血尿、高血圧
• 蛋白尿はnonselective

成因

• 1. 一次性
• 2. 二次性

• 1. HIV感染、ヘロイン
• 2. 他の糸球体腎炎に続発
• 3. ネフロン喪失に続発するmaladaptation
• 4. 足細胞に発現する細胞骨格に関連する蛋白質(ネフリン)

病理

• 光学顕微鏡

• 巣状かつ分節性の硬化病変

• メサンギウム基質、毛細管腔の閉塞、ヒアリン・脂質滴の沈着

• 蛍光抗体法…IgMと補体成分（特にC３）の沈着が認められる
• 電子顕微鏡…上皮細胞に足突起の融合が見られ、ところどころで上皮細胞そのものが脱落し、基底膜が丸出しになっている所見も認められる

予後

• 予後不良
• ステロイドが効かない
• 腎移植後の再発が多い

「FSGS」

　　[★] 巣状分節性糸球体硬化症

同

focal segmental glomerulosclerosis

同

focal segmental glomerulosclerosis

同

focal and segmental glomerulosclerosis

「focal sclerosing glomerulonephritis」

　　[★]

巣状糸球体硬化症

関

focal glomerulosclerosis、focal segmental glomerulosclerosis

「focal」

　　[★]

• adj.

• 焦点の、焦点を通る
• (病変が)限局性の、局所の、病巣の、巣状の

関

circumscribed、definite、focal point、focally、foci、focus、local、localized、locally、nidal、nidus、topical、topically

　 　 　

「segmental」

　　[★]

• adj.

• 分節状の、分節性の、分節型の、分節の、体節の、区域の

関

area、metameric、region、segment、segmentally、somite、somitic

　

「segment」

　　[★]

• n.

• セグメント、区域、分節、体節

関

area、metameric、region、segmental、somite、somitic