膜性増殖性糸球体腎炎 membranoproliferative glomerulonephritis

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/12 16:41:05」(JST)

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Membranoproliferative glomerulonephritis ("MPGN"), also known as mesangiocapillary glomerulonephritis,^[1] is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening,^[2] activating complement and damaging the glomeruli.

MPGN accounts for approximately 4% of primary renal causes of nephritic syndrome in children and 7% in adults.^[3]

It should not be confused with membranous glomerulonephritis, a condition in where the basement membrane is thickened, but the mesangium is not.

Pathology[edit]

Renal corpuscle. Membranoproliferative glomerulonephritis involves deposits at the intraglomerular mesangium (#5a) which leads to "splitting" of the glomerular basement membrane (#1).

Membranoproliferative glomerulonephritis involves deposits at the intraglomerular mesangium.

It is also the main hepatitis C associated nephropathy.

The histomorphologic differential diagnosis includes transplant glomerulopathy and thrombotic microangiopathies.

Appearance[edit]

The GBM is rebuilt on top of the deposits, causing a "tram tracking" appearance under the microscope.^[4] Mesangial cellularity is increased.^[5]

Type[edit]

There are three types of MPGN.

Type I[edit]

Type I the most common by far, is caused by immune complexes depositing in the kidney. It is characterised by subendothelial and mesangial immune deposits.

It is believed to be associated with the classical complement pathway.^[6]

Type II[edit]

Type II (sometimes also called "dense deposit disease"^[7]) is similar to type I. However, it is believed to be associated with the alternative complement pathway.^[8]^[9]

Spontaneous remissions of MPGN II are rare, approximately half of those affected with MPGN II will progress to end stage renal disease within 10 years.^[10]

In many cases, people with MPGN II can develop drusen which is caused by same deposits within the Bruch's membrane beneath the retinal pigment epithelium (RPE) layer of the eye. Over time vision can deteriorate and subretinal neovascular membranes, macular detachment, and central serous retinopathy develop.^[11]

A report in 2007 suggests that dense deposit disease may not be a membranoproliferative glomerulonephritis subtype.^[12] A 2012 review considers DDD to be in a continuum with C3 glomerulonephritis.^[13]

( See also : Eculizumab#Dense-deposit disease (DDD) )

Type III[edit]

Type III is very rare, it is characterized by a mixture of subepithelial deposits and the typical pathological findings of Type I disease.

A candidate gene has been identified on chromosome 1.^[14]

Complement component 3 is seen under immunofluorescence.^[15]

References[edit]

^ Colville D, Guymer R, Sinclair RA, Savige J (August 2003). "Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type II ("dense deposit disease")". Am. J. Kidney Dis. 42 (2): E2–5. doi:10.1016/S0272-6386(03)00665-6. PMID 12900843.
^ "membranoproliferative glomerulonephritis" at Dorland's Medical Dictionary
^ Habib R, Gubler MC, Loirat C, Mäiz HB, Levy M (1975). "Dense deposit disease: a variant of membranoproliferative glomerulonephritis". Kidney Int. 7 (4): 204–15. doi:10.1038/ki.1975.32. PMID 1095806.
^ "Membranoproliferative_glomerulonephritis_type_I of the Kidney". Retrieved 2008-11-25.
^ "Renal Pathology". Retrieved 2008-11-25.
^ West CD, McAdams AJ (March 1998). "Glomerular paramesangial deposits: association with hypocomplementemia in membranoproliferative glomerulonephritis types I and III". Am. J. Kidney Dis. 31 (3): 427–34. doi:10.1053/ajkd.1998.v31.pm9506679. PMID 9506679.
^ "Final Diagnosis — Case 148". Retrieved 2008-11-25.
^ Rose KL, Paixao-Cavalcante D, Fish J, et al. (February 2008). "Factor I is required for the development of membranoproliferative glomerulonephritis in factor H-deficient mice". J. Clin. Invest. 118 (2): 608–18. doi:10.1172/JCI32525. PMC 2200299. PMID 18202746.
^ Licht C, Schlötzer-Schrehardt U, Kirschfink M, Zipfel PF, Hoppe B (January 2007). "MPGN II--genetically determined by defective complement regulation?". Pediatr. Nephrol. 22 (1): 2–9. doi:10.1007/s00467-006-0299-8. PMID 17024390.
^ Swainson CP, Robson JS, Thomson D, MacDonald MK (1983). "Mesangiocapillary glomerulonephritis: a long-term study of 40 cases". J. Pathol. 141 (4): 449–68. doi:10.1002/path.1711410404. PMID 6363655.
^ Colville D, Guymer R, Sinclair RA, Savige J (2003). "Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type II ("dense deposit disease")". Am. J. Kidney Dis. 42 (2): E2–5. doi:10.1016/S0272-6386(03)00665-6. PMID 12900843.
^ Patrick D Walker, Franco Ferrario, Kensuke Joh, Stephen M Bonsib (2007). "Dense deposit disease is not a membranoproliferative glomerulonephritis". Modern Pathology. 20 (6): 605–616. doi:10.1038/modpathol.3800773. PMID 17396142
^ Sethi, Fervenza, S, FC (2012). "Membranoproliferative glomerulonephritis - a new look at an old entity". N Engl J Med 366: 1119–1131. doi:10.1056/NEJMra1108178.
^ Neary JJ, Conlon PJ, Croke D, et al. (August 2002). "Linkage of a gene causing familial membranoproliferative glomerulonephritis type III to chromosome 1". J. Am. Soc. Nephrol. 13 (8): 2052–7. doi:10.1097/01.ASN.0000022006.49966.F8. PMID 12138136.
^ Neary J, Dorman A, Campbell E, Keogan M, Conlon P (July 2002). "Familial membranoproliferative glomerulonephritis type III". Am. J. Kidney Dis. 40 (1): E1. doi:10.1053/ajkd.2002.33932. PMID 12087587.

External links[edit]

Glomerulonephritis, Membranoproliferative Types I,II,III at eMedicine
Corchado, Johnny Cruz; Smith, Richard JH (July 2007). "Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II". In Pagon RA, Bird TD, Dolan CR, et al.. GeneReviews. Seattle WA: University of Washington. PMID 20301598.
Membranoproliferative_GN at Nephropathology tutorial
MP GN Pathophysiology discusses the nephritic auto-antibodies/factors

UpToDate Contents

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1. 膜性増殖性糸球体腎炎の臨床像、分類、および原因 clinical presentation classification and causes of membranoproliferative glomerulonephritis
2. 膜性増殖性糸球体腎炎の評価および治療 evaluation and treatment of membranoproliferative glomerulonephritis
3. C型肝炎ウイルス感染関連腎疾患の概要 overview of renal disease associated with hepatitis c virus infection
4. 移植後の免疫複合体媒介性の特発性膜性増殖性糸球体腎炎（MPGN）再発 recurrence of idiopathic immune complex mediated membranoproliferative glomerulonephritis mpgn after transplantation
5. C3糸球体症の移植後再発 recurrence of c3 glomerulopathies after transplantation

English Journal

C4d immunohistochemical staining is a sensitive method to confirm immunoreactant deposition in formalin-fixed paraffin-embedded tissue in membranous glomerulonephritis.

Val-Bernal JF, Garijo MF, Val D, Rodrigo E, Arias M.SourceDepartment of Anatomical Pathology, Marques de Valdecilla University Hospital, Medical Faculty, University of Cantabria, Santander, Spain. apavbj@humv.es.
Histology and histopathology.Histol Histopathol.2011 Nov;26(11):1391-7.
Although the diagnosis of membranous glomerulonephritis (MGN) may be suspected on routine histology of formalin-fixed paraffin-embedded tissue, fresh-frozen tissue must be used to show the immunologic nature of the process by direct immunofluorescence (IF). The efficiency of IF or immunoperoxidase (
PMID 21938676

Macrophages are essential contributors to kidney injury in murine cryoglobulinemic membranoproliferative glomerulonephritis.

Guo S, Wietecha TA, Hudkins KL, Kida Y, Spencer MW, Pichaiwong W, Kojima I, Duffield JS, Alpers CE.SourceDepartment of Pathology, University of Washington, Seattle, Washington, USA.
Kidney international.Kidney Int.2011 Nov;80(9):946-58. doi: 10.1038/ki.2011.249. Epub 2011 Aug 3.
Mice transgenic for thymic stromal lymphopoietin (TSLP), under regulation of the lymphocyte-specific promoter Lck, develop cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN) similar to the disease in patients. To determine whether infiltrating macrophages, a hallmark of this diseas
PMID 21814168

Japanese Journal

今月の症例 Rituximab併用化学療法に反応したMALTリンパ腫関連クリオグロブリン陽性膜性増殖性糸球体腎炎の1例

倉重眞大,横尾隆,宮崎陽一 [他]
日本内科学会雑誌 100(4), 1054-1057, 2011-04-10
NAID 40018816585

Clinicopathological Study on Hepatitis C Virus-associated Glomerulonephritis without Hepatitis C Virus in the Blood

Yamabe Hideaki,Nakamura Norio,Shimada Michiko,Murakami Reiichi,Fujita Takeshi,Shimaya Yuko,Kitajima Maiko,Urushizaka Mayumi
Internal Medicine 49(14), 1321-1323, 2010
Purpose Patients with hepatitis C virus (HCV)-associated glomerulonephritis in whom HCV RNA was not detected in the blood have been reported. We attempted to uncover the differences between HCV RNA-ne …
NAID 130000299534

Related Pictures

★リンクテーブル★

リンク元	「膜性増殖性糸球体腎炎」「糸球体選択指数」「低補体血症」「membranoproliferative glomerulonephritis」
関連記事	「MP」「MPG」

「膜性増殖性糸球体腎炎」

Membranoproliferative glomerulonephritis
	Classification and external resources
	; Micrograph of glomerulus in membranoproliferative glomerulonephritis with increased mesangial matrix and increased mesangial cellularity. Kidney biopsy. PAS stain.
ICD-10	N00-N08 with .5 and .6 suffix
ICD-9	581.2, 582.2, 583.2
OMIM	609814 305800
DiseasesDB	34457
MedlinePlus	000475
eMedicine	med/887
MeSH	D015432
GeneReviews	Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II;

　　[★]

英: membranoproliferative glomerulonephritis, MPGN
同: メサンギウム毛細管性糸球体腎炎 mesangiocapillary glomerulonephritis MCGN
関: 糸球体腎炎、糸球体疾患

概念

糸球体腎炎の病理診断名の一つ。
光顕的に(1)メサンギウム細胞・メサンギウム基質の増殖、(2)びまん性の糸球体基底膜の二重化　→　糸球体基底膜上皮細胞の障害と糸球体の炎症を兼ね備える。
しかも原発性であること。

分類

WHO分類

電顕所見よる高電子密度沈着物の部位で分類

I型：内皮下腔

全周性のメサンギウム間入とメサンギウム領域、内皮細胞下腔の高電子密度沈着物がみられる

II型：糸球体基底膜内
III型：内皮細胞下腔と上皮細胞下腔の両方

頻度

ネフローゼ症候群

膜性増殖性糸球体腎炎が原因となって生じるネフローゼ症候群の小児10%、成人5%を占める。

病因

50%の症例に先行感染が見られるという、、、
何らかの原因がきっかけで補体(C3やC4)が関与することになり、病変を形成　→　50～70%が低補体血症を示す。

病因による分類

特発性
二次性

I型　　：細菌性心内膜炎、B型肝炎ウイルス(成人)、C型肝炎ウイルス(±クリオグロブリン血症)、クリオグロブリン血症、マラリア、シャント腎炎
II型　：partial lipodystrophy
III型：ループス腎炎

沈着物

I,III型：免疫複合体、C3、C4
II型　：C3　←　免疫複合体ではない。　→　移植腎に再発するため血液中の未知物質が原因

II型はI,III型とことなり、デンスデポジット病(dense deposit disease)と呼ばれる。

補体の活性経路

I, III型：C3,C4,IC　　　　　　　：classical pathway
II型　　：C3 nephritic factor：alternative pathway

症状

血尿(肉眼的血尿, 1/3の症例)・蛋白尿、腎機能低下(糸球体濾過量の低下)(1/3の症例)、高血圧(1/3の症例)
糸球体腎炎＋ネフローゼ症候群がみられる

チャンス蛋白尿やチャンス血尿で発見される(らしい・・・)

ネフローゼ症候群(50%の症例)
急性糸球体腎炎(20%の症例)

検査

尿検査

血尿、蛋白尿、赤血球円柱、顆粒円柱

免疫血清学

低補体血症　→　症例の70%

I型：CH50, C3, C4, C1q　の低下
II型：C3, CH50の持続低下(75％の症例)

病理所見

[show details]

光顕所見

びまん性メザンギウム細胞およびメザンギウム細胞基質の増加
分葉化
糸球体毛細血管係蹄腔の狭小化
基底膜の二重化(double contour)、tram track

蛍光所見

IgG、C3が係蹄壁にfringe pattern

電顕所見

I型　　：内皮下沈着物　←　糸球体の内側
II型　：(Dense Deposit Disease)基底膜の緻密層(lamina densa)にリボン状の広範な沈着物　←　基底膜の真ん中
III型：内皮下、上皮下、基底膜内に沈着物

治療

治療は、副腎皮質ステロイド薬、免疫抑制薬、抗血小板薬、抗凝固薬などを併用する。　→　多剤併用(カクテル)療法、時にステロイドパルス療法が有効

予後

進行性で予後は不良
10年後に50%が腎不全に進行(10年腎生存率50-60%)
予後不良例：「硬化病変の高度なもの」、「半月体・尿細管－間質病変が高度なもの。」
I型よりII型は予後不良。II型は半月体形成する。　←　予後が悪いことを裏付け。　
II型は移植腎に再発(ほぼ100%)

国試

103A042

「糸球体選択指数」

　　[★]

英: glomerular selectivity index
同: 選択指数 selectivity index
関: 蛋白尿; 尿蛋白質選択性 selectivity of urine protein; 非選択性蛋白尿 nonselective proteinuria

定義

選択指数(S.I.) = C_IgG()/C_transferrin
SI(selectivity index)＝(尿中IgG/血清IgG)/(尿中Tf/血清Tf)。

M.W.： IgG=150kDa, トランスフェリン=80kDa

Cはクリアランスで、大きいほどよく尿中から排泄されていることを示す。

判定

SI ＜ 0.1 →　高選択性
SI ＞ 0.5　→　低選択性

選択性の高い疾患：

微小変化型ネフローゼ症候群 MCNS

選択性の低い疾患：

必要なパラメータ

血清中Ig濃度、血清中トランスフェリン濃度
尿中Ig濃度、尿中トランスフェリン濃度

参考

計算できる

http://www.med.osaka-u.ac.jp/pub/imed3/lab_2/page4/page4-7.html

http://www.muikamachi-hp.muika.niigata.jp/ClinCal/SI.html

「低補体血症」

　　[★]

英: hypocomplementemia
関: 補体

原因

コレステロール塞栓症、悪性関節リウマチ、ループス腎炎、溶連菌感染後急性糸球体腎炎、膜性増殖性糸球体腎炎、クリオグロブリン血症、C肝炎ウイルス関連腎症

低補体血症＋腎炎

YN.E-53

「membranoproliferative glomerulonephritis」

　　[★] 膜性増殖性糸球体腎炎 MPGN

「MP」

　　[★]

「MPG」

　　[★]

同: mean pressure gradient, 平均圧較差

[pmid12900843-1] Colville D, Guymer R, Sinclair RA, Savige J (August 2003). "Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type II ("dense deposit disease")". Am. J. Kidney Dis. 42 (2): E2–5. doi:10.1016/S0272-6386(03)00665-6. PMID 12900843.

[2] "membranoproliferative glomerulonephritis" at Dorland's Medical Dictionary

[3] Habib R, Gubler MC, Loirat C, Mäiz HB, Levy M (1975). "Dense deposit disease: a variant of membranoproliferative glomerulonephritis". Kidney Int. 7 (4): 204–15. doi:10.1038/ki.1975.32. PMID 1095806.

[4] "Membranoproliferative_glomerulonephritis_type_I of the Kidney". Retrieved 2008-11-25.

[5] "Renal Pathology". Retrieved 2008-11-25.

[pmid9506679-6] West CD, McAdams AJ (March 1998). "Glomerular paramesangial deposits: association with hypocomplementemia in membranoproliferative glomerulonephritis types I and III". Am. J. Kidney Dis. 31 (3): 427–34. doi:10.1053/ajkd.1998.v31.pm9506679. PMID 9506679.

[urlFinal_Diagnosis_--_Case_148-7] "Final Diagnosis — Case 148". Retrieved 2008-11-25.

[pmid18202746-8] Rose KL, Paixao-Cavalcante D, Fish J, et al. (February 2008). "Factor I is required for the development of membranoproliferative glomerulonephritis in factor H-deficient mice". J. Clin. Invest. 118 (2): 608–18. doi:10.1172/JCI32525. PMC 2200299. PMID 18202746.

[pmid17024390-9] Licht C, Schlötzer-Schrehardt U, Kirschfink M, Zipfel PF, Hoppe B (January 2007). "MPGN II--genetically determined by defective complement regulation?". Pediatr. Nephrol. 22 (1): 2–9. doi:10.1007/s00467-006-0299-8. PMID 17024390.

[10] Swainson CP, Robson JS, Thomson D, MacDonald MK (1983). "Mesangiocapillary glomerulonephritis: a long-term study of 40 cases". J. Pathol. 141 (4): 449–68. doi:10.1002/path.1711410404. PMID 6363655.

[11] Colville D, Guymer R, Sinclair RA, Savige J (2003). "Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type II ("dense deposit disease")". Am. J. Kidney Dis. 42 (2): E2–5. doi:10.1016/S0272-6386(03)00665-6. PMID 12900843.

[12] Patrick D Walker, Franco Ferrario, Kensuke Joh, Stephen M Bonsib (2007). "Dense deposit disease is not a membranoproliferative glomerulonephritis". Modern Pathology. 20 (6): 605–616. doi:10.1038/modpathol.3800773. PMID 17396142

[Sethi2012-13] Sethi, Fervenza, S, FC (2012). "Membranoproliferative glomerulonephritis - a new look at an old entity". N Engl J Med 366: 1119–1131. doi:10.1056/NEJMra1108178.

[pmid12138136-14] Neary JJ, Conlon PJ, Croke D, et al. (August 2002). "Linkage of a gene causing familial membranoproliferative glomerulonephritis type III to chromosome 1". J. Am. Soc. Nephrol. 13 (8): 2052–7. doi:10.1097/01.ASN.0000022006.49966.F8. PMID 12138136.

[15] Neary J, Dorman A, Campbell E, Keogan M, Conlon P (July 2002). "Familial membranoproliferative glomerulonephritis type III". Am. J. Kidney Dis. 40 (1): E1. doi:10.1053/ajkd.2002.33932. PMID 12087587.

Membranoproliferative glomerulonephritis
Classification and external resources
Micrograph of glomerulus in membranoproliferative glomerulonephritis with increased mesangial matrix and increased mesangial cellularity. Kidney biopsy. PAS stain.
ICD-10	N00-N08 with .5 and .6 suffix
ICD-9	581.2, 582.2, 583.2
OMIM	609814 305800
DiseasesDB	34457
MedlinePlus	000475
eMedicine	med/887
MeSH	D015432
GeneReviews	Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II

匿名

検索

案内

MPGN