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relating to or made of or similar to a membrane; "membranous lining"
characterized by formation of a membrane (or something resembling a membrane); "membranous gastritis" (同)membrane-forming
nephritis marked by inflammation of the glomeruli of the kidney; characterized by decreased production of urine and by the presence of blood and protein in the urine and by edema

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/09 14:06:29」(JST)

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Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly patients between ages of 30 and 50 years, usually Caucasian.

It is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) being the most common.^[1]

Terminology

The closely related terms membranous nephropathy^[2] and membranous glomerulopathy^[3] both refer to a similar constellation but without the assumption of inflammation.

Membranous nephritis (in which inflammation is implied, but the glomerulus not explicitly mentioned) is less common, but the phrase is occasionally encountered.^[4] These conditions are usually considered together.

By contrast, membranoproliferative glomerulonephritis has a similar name, but is considered a separate condition with a distinctly different causality. Membranoproliferative glomerulonephritis involves the basement membrane and mesangium, while membranous glomerulonephritis involves the basement membrane but not the mesangium. (Membranoproliferative glomerulonephritis has the alternate name "mesangiocapillary glomerulonephritis", to emphasize its mesangial character.)

Signs and symptoms

Some people may present as nephrotic syndrome with proteinuria, edema with or without renal failure. Others may be asymptomatic and may be picked up on screening or urinalysis as having proteinuria. A definitive diagnosis of membranous nephropathy requires a kidney biopsy.

Causes and classification

Primary/idiopathic

85% of MGN cases are classified as primary membranous glomerulonephritis—that is to say, the cause of the disease is idiopathic (of unknown origin or cause). This can also be referred to as idiopathic membranous nephropathy. One study has identified antibodies to an M-type phospholipase A₂ receptor in 70% (26 of 37) cases evaluated.^[5] Other studies have implicated neutral endopeptidase and cationic bovine serum albumin as antigens.^[6]

Secondary

The remainder is secondary due to:

autoimmune conditions (e.g., systemic lupus erythematosus^[7])
infections (e.g., syphilis, malaria, hepatitis B, hepatitis C)
drugs (e.g., captopril, NSAIDs, penicillamine, probenecid).
inorganic salts (e.g. gold, mercury).
tumors, frequently solid tumors of the lung and colon; hematological malignancies such as chronic lymphocytic leukemia are less common.^[8]

Pathogenesis

Immune complexes (black) are deposited in a thickened basement membrane creating a "spike and dome" appearance on electron microscopy.

MGN is caused by immune complex formation in the glomerulus. The immune complexes are formed by binding of antibodies to antigens in the glomerular basement membrane. The antigens may be part of the basement membrane, or deposited from elsewhere by the systemic circulation.

The immune complex serves as an activator that triggers a response from the C5b - C9 complements, which form a membrane attack complex (MAC) on the glomerular epithelial cells. This, in turn, stimulates release of proteases and oxidants by the mesangial and epithelial cells, damaging the capillary walls and causing them to become "leaky". In addition, the epithelial cells also seem to secrete an unknown mediator that reduces nephrin synthesis and distribution.

Morphology

The defining point of MGN is the presence of subepithelial immunoglobulin-containing deposits along the glomerular basement membrane (GBM).

By light microscopy, the basement membrane is observed to be diffusely thickened. Using Jones' stain, the GBM appears to have a "spiked" or "holey" appearance.

On electron microscopy, subepithelial deposits that nestle against the glomerular basement membrane seems to be the cause of the thickening. Also, the podocytes lose their foot processes. As the disease progresses, the deposits will eventually be cleared, leaving cavities in the basement membrane. These cavities will later be filled with basement membrane-like material, and if the disease continues even further, the glomeruli will become sclerosed and finally hyalinized.

Immunoflourescence microscopy will reveal typical granular deposition of immunoglobulins and complement along the basement membrane.^[9]

Although it usually affects the entire glomerulus, it can affect parts of the glomerulus in some cases.^[10]

Treatment

Treatment of secondary membranous nephropathy is guided by the treatment of the original disease. For treatment of idiopathic membranous nephropathy, the treatment options include immunosuppressive drugs and non-specific anti-proteinuric measures. Recommended first line therapy often includes: cyclophosphamide alternating with a corticosteroid.^[11]

Immunosuppressive therapy

Corticosteroids: They have been tried with mixed results, with one study showing prevention of progression to renal failure without improvement in proteinuria.
Chlorambucil
Cyclosporine^[12]
Tacrolimus
Cyclophosphamide
Mycophenolate mofetil

Perhaps the most difficult aspect of membranous glomerulonephritis is deciding which people to treat with immunosuppressive therapy as opposed to simple "background" or anti-proteinuric therapies. A large part of this difficulty is due to a lack of ability to predict which people will progress to end-stage renal disease, or renal disease severe enough to require dialysis. Because the above medications carry risk, treatment should not be initiated without careful consideration as to risk/benefit profile. Of note, corticosteroids (typically Prednisone) alone are of little benefit. They should be combined with one of the other 5 medications, each of which, along with prednisone, has shown some benefit in slowing down progression of membranous nephropathy. It must be kept in mind, however, that each of the 5 medications also carry their own risks, on top of prednisone.

The twin aims of treating membranous nephropathy are first to induce a remission of the nephrotic syndrome and second to prevent the development of endstage renal failure. A meta-analysis of four randomized controlled studies comparing treatments of membranous nephropathy showed that regimes comprising chlorambucil or cyclophosphamide, either alone or with steroids, were more effective than symptomatic treatment or treatment with steroids alone in inducing remission of the nephrotic syndrome.

Prognosis

About a third of patients have spontaneous remission, another third progress to require dialysis and the last third continue to have proteinuria, without progression of renal failure.

References

^ Abeera Mansur, MD (May 2012). "Membranous Glomerulonephritis".
^ Passerini P, Ponticelli C (July 2003). "Corticosteroids, cyclophosphamide, and chlorambucil therapy of membranous nephropathy". Semin. Nephrol. 23 (4): 355–61. doi:10.1016/S0270-9295(03)00052-4. PMID 12923723.
^ Markowitz GS (May 2001). "Membranous glomerulopathy: emphasis on secondary forms and disease variants". Adv Anat Pathol 8 (3): 119–25. doi:10.1097/00125480-200105000-00001. PMID 11345236.
^ Hallegua D, Wallace DJ, Metzger AL, Rinaldi RZ, Klinenberg JR (2000). "Cyclosporine for lupus membranous nephritis: experience with ten patients and review of the literature". Lupus 9 (4): 241–51. doi:10.1191/096120300680198935. PMID 10866094.
^ Beck, LH; Bonegio, RGB; Lambeau, G; Beck, DM; Powell, DW; Cummins, TD;, Klein, JB; Salant, DJ. (July 2, 2009). "M-Type Phospholipase A2 Receptor as Target Antigen in Idiopathic Membranous Nephropathy". The New England Journal of Medicine 361 (1): 11–21. doi:10.1056/NEJMoa0810457. PMC 2762083. PMID 19571279.
^ Ronco P, Debiec H (2012) Pathogenesis of membranous nephropathy: recent advances and future challenges. Nat Rev Nephrol doi:10.1038/nrneph.2012.35.
^ "Renal Pathology". Retrieved 2008-11-25.
^ Ziakas PD, Giannouli S, Psimenou E, Nakopoulou L, Voulgarelis M (July 2004). "Membranous glomerulonephritis in chronic lymphocytic leukemia". Am. J. Hematol. 76 (3): 271–4. doi:10.1002/ajh.20109. PMID 15224365.
^ "Renal Pathology". Retrieved 2008-11-25.
^ Obana M, Nakanishi K, Sako M et al. (July 2006). "Segmental membranous glomerulonephritis in children: comparison with global membranous glomerulonephritis". Clin J Am Soc Nephrol 1 (4): 723–9. doi:10.2215/CJN.01211005. PMID 17699279.
^ Chen, Y; Schieppati, A; Chen, X; Cai, G; Zamora, J; Giuliano, GA; Braun, N; Perna, A (Oct 16, 2014). "Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.". The Cochrane database of systematic reviews 10: CD004293. doi:10.1002/14651858.CD004293.pub3. PMID 25318831.
^ Goumenos DS, Katopodis KP, Passadakis P et al. (2007). "Corticosteroids and ciclosporin A in idiopathic membranous nephropathy: higher remission rates of nephrotic syndrome and less adverse reactions than after traditional treatment with cytotoxic drugs". Am. J. Nephrol. 27 (3): 226–31. doi:10.1159/000101367. PMID 17389782.

UpToDate Contents

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1. 特発性膜性腎症の治療 treatment of idiopathic membranous nephropathy
2. 膜性腎症の原因および診断 causes and diagnosis of membranous nephropathy
3. 膜性腎症と腎移植 membranous nephropathy and renal transplantation
4. 重症蛋白尿およびネフローゼ症候群の概要 overview of heavy proteinuria and the nephrotic syndrome
5. 特発性膜性腎症の治療における代替剤 alternative agents in the treatment of idiopathic membranous nephropathy

English Journal

Out of Africa: Complete and partial remissions as a combined outcome in patients with idiopathic membranous glomerulonephritis in Cape Town.

Ameh OI1, Swanepoel CR1, Aderibigbe A2, Kengne AP3, Okpechi IG1.
Nephrology (Carlton, Vic.).Nephrology (Carlton).2016 Dec;21(12):1010-1016. doi: 10.1111/nep.12703.
AIM: Remission outcomes among patients with idiopathic membranous glomerulonephritis is unknown in Africa. We sought to determine remission outcomes in a cohort of South African adult patients with IMGN.METHODS: This was a retrospective review of patients with biopsy-proven IMGN over a 10 year per
PMID 26706191

Kidney disease in the elderly: biopsy based data from 14 renal centers in Poland.

Perkowska-Ptasinska A1, Deborska-Materkowska D2, Bartczak A3, Stompor T4, Liberek T5, Bullo-Piontecka B5, Wasinska A6, Serwacka A6, Klinger M7, Chyl J8, Kuriga M9, Malecki R10, Marczewski K11, Hryniewicz B12, Gregorczyk T13, Wieliczko M14, Niemczyk S15, Rostkowska O2, Paczek L16, Durlik M2.
BMC nephrology.BMC Nephrol.2016 Nov 25;17(1):194.
BACKGROUND: Longer life expectancy is associated with an increasing prevalence of kidney disease. Aging itself may cause renal damage, but the spectrum of kidney disorders that affect elderly patients is diverse. Few studies, mostly form US, Asia and West Europe found differences in the prevalence o
PMID 27884116

Triptolide Attenuates Inflammatory Response in Membranous Glomerulo-Nephritis Rat via Downregulation of NF-κB Signaling Pathway.

Zhou Y1, Hong Y, Huang H.
Kidney & blood pressure research.Kidney Blood Press Res.2016 Nov 23;41(6):901-910. [Epub ahead of print]
BACKGROUND/AIMS: Triptolide (TPL), a main active ingredient of Tripterygium wilfordii has been shown to exert anti-inflammatory effect. The role of TPL on glomerular diseases remains unclear.METHODS: This study aims to investigate the potential anti-inflammatory effect of TPL in rats with membranous
PMID 27871079

Japanese Journal

Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

Kimura Junpei,Ichii Osamu,Otsuka Saori,Sasaki Hayato,Hashimoto Yoshiharu,Kon Yasuhiro
American Journal Of Nephrology 38(1), 27-38, 2013-07
… Background: Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). … BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. …
NAID 120005322430

症例膜性腎症に著明な半月体形成を合併した溶連菌感染後糸球体腎炎の1例

松田潤,長山郁恵,山口嘉土 [他]
The Japanese journal of nephrology = 日本腎臓学会誌 55(4), 567-573, 2013
NAID 40019754148

Antiribosomal-P protein antibodies are associated with proliferative glomerulonephritis more strongly than with membranous glomerulonephritis in Japanese patients with systemic lupus erythematosus

YOSHIO Taku,OKAMOTO Hiroshi,ONISHI Sachiko,MINOTA Seiji
Modern rheumatology 22(3), 488-490, 2012-06-01
NAID 10030782641

Related Pictures

★リンクテーブル★

リンク元	「膜性腎症」「membranous glomerulopathy」「Heymann nephritis」「membranous glomerulonephropathy」「idiopathic membranous nephropathy」
拡張検索	「idiopathic membranous glomerulonephritis」
関連記事	「membranous」「glomerulonephritis」

「膜性腎症」

Membranous glomerulonephritis
	Micrograph of membranous nephropathy showing prominent glomerular basement membrane spikes. Jones' stain.
Classification and external resources
Specialty	urology
ICD-10	N03.2
ICD-9-CM	583.1
DiseasesDB	7970
eMedicine	med/885
MeSH	D015433

　　[★]

membranous
英: membranous nephropathy, MN
同: 膜性糸球体腎炎 membranous glomerulonephritis, membranous GN, MGN
関: ネフローゼ症候群

まとめ

膜性腎症は免疫複合体が糸球体基底膜上皮下に沈着することで基底膜の肥厚をきたす疾患である。中年以降(30-40歳以降)の男性に多い。自覚症状なしにネフローゼ症候群を来たし、ネフローゼ症候群の原因として成人では30%、小児では5%を占める。病因としては特発性と続発性があるが、免疫複合体の抗原が不明な特発性が大部分(85%)を占め、残りは感染症(B型肝炎、梅毒、住血吸虫マラリア)、膠原病(SLE)、悪性腫瘍、無機金属(金、水銀)、薬剤(ペニシラミン、カプトプリル、NSAID)などによる続発性である。病理組織像では光顕的に糸球体膜の重層化・二重化・肥厚が認められ、PAM染色で糸球体基底膜上皮下にスパイク状・顆粒状の沈着物が認められる。これらは蛍光顕微鏡ではIgG、C3の沈着として認められる。電顕的には電子高密度沈着物(免疫複合体)として認められる。自覚症状はなく検診などで蛋白尿陽性として見いだされることが多い。診断には腎生検の所見による。治療は特発性の場合、無症候性であれば経過観察、ネフローゼ症候群が存在していればステロイドによる治療を行う。二次性の場合は原因疾患の治療も行う。治療抵抗例では免疫抑制薬、抗血小板薬、抗凝固療法を行う。経過は緩徐であり、予後は良好であることが多い。症例の2/3は緩徐進行、1/3は自然緩解する。(YN.E-50 SPE.599)

概念

糸球体腎炎の病理診断名の一つ
糸球体基底膜の上皮側にびまん性の免疫複合体が沈着し、基底膜が肥厚する疾患。
(1)糸球体基底膜のびまん性肥厚、(2)糸球体基底膜上皮下へのびまん性沈着
ネフローゼ症候群を来す。成人ネフローゼの典型例

疫学

中年以降(30-50%)の男性に好発。　30-40歳代の男性に多い(QB.E-173)。
健診で発覚(チャンス蛋白尿)
ネフローゼ症候群の原因となる。ネフローゼ症候群のうちそれぞれ占める割合は成人30%、小児5%。 (YN.E-50)

分類

病因による分類

特発性(85%)　←　免疫複合体の抗原が不明
続発性

感染症(B型肝炎、梅毒、住血吸虫症、マラリア)
膠原病(SLE)
悪性腫瘍(扁平上皮癌：肺癌、大腸癌、悪性黒色腫)
inorganic salts(金、水銀)
薬剤(penicillamine, captopril, NSAID)

APT.241

B型肝炎ウイルス、C型肝炎ウイルス、腫瘍、薬物(NSAID)、SLE

病理

蛍光抗体法

糸球体基底膜のびまん性肥厚　　→　糸球体膜の重層化・二重化・肥厚
免疫複合体が糸球体基底膜上皮下に沈着　←　糸球体の外側　　→　スパイク(PAM染色で)　、　granular pattern(IgG)
メサンギウム領域の細胞増殖(-)

病態生理

80%がネフローゼ症候群で発症し、あとは無症候性蛋白尿(QB.E-173)

症状

蛋白尿　←　泡立つことで気づかれるらしい
ネフローゼ症候群(25%を占める)
血尿（－）

検査

血液検査

ネフローゼ症候群を来す場合には低蛋白血症、低アルブミン血症

尿検査

尿蛋白陽性。

腎生検

光学顕微鏡(PAM染色)：基底膜の肥厚

[show details]

蛍光顕微鏡(蛍光抗体法)：IgG、C3よりなる免疫複合体が糸球体上皮下腔に顆粒状に沈着

[show details]

電子顕微鏡

糸球体基底膜上皮下に高電子密度の顆粒状沈着物

[show details]

診断

膜性腎症の診断は腎生検でのみなされる。原因不明のネフローゼ症候群には腎生検を提案している。(uptodate)

蛋白尿に対する検査を行う→ネフローゼ症候群　→　uptodate Serologic tests in the evaluation of nephrotic syndrome
膜性腎症の原因を検索するために以下の検査を行う：自己抗体、血清C3(普通は正常)、血清学的ウイルス検査(B型肝炎ウイルス、C型肝炎ウイルス)、悪性腫瘍スクリーニング　(uptodate)