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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/03/14 14:55:07」(JST)

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Proteinuria (/proʊtiːˈnʊəriə/ or /proʊtiːˈnjʊəriə/; from protein and urine) means the presence of an excess of serum proteins in the urine. The excess protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine (bilirubinuria),^[1] retrograde ejaculation,^[2] pneumaturia (air bubbles in the urine) due to a fistula,^[3] or drugs such as pyridium.^[1]

Causes[edit]

There are three main mechanisms to cause proteinuria:

Due to disease in glomerulus
Because of increased quantity of proteins in serum (overflow proteinuria)
Due to low reabsorption at proximal tubule (Fanconi syndrome)

Proteinuria can also be caused by certain biological agents, such as bevacizumab (Avastin) used in cancer treatment, or by excessive fluid intake (drinking in excess of 4 litres of water per day).^[4]^[5]

Measurement[edit]

Protein dipstick grading
Designation	Approx. amount
Designation	Concentration^[6]	Daily^[7]
Trace	5–20 mg/dL
1+	30 mg/dL	Less than 0.5 g/day
2+	100 mg/dL	0.5–1 g/day
3+	300 mg/dL	1–2 g/day
4+	More than 300 mg/dL	More than 2 g/day

Conventionally, proteinuria is diagnosed by a simple dipstick test, although it is possible for the test to give a false negative reading,^[8] even with nephrotic range proteinuria if the urine is dilute.^{[citation needed]} False negatives may also occur if the protein in the urine is composed mainly of globulins or Bence-Jones proteins because the reagent on the test strips, bromphenol blue, is highly specific for albumin.^[9]^[10] Traditionally, dipstick protein tests would be quantified by measuring the total quantity of protein in a 24-hour urine collection test, and abnormal globulins by specific requests for protein electrophoresis.^[1]^[11] Trace results may be produced in response to excretion of Tamm-Horsfall mucoprotein.

Recent technologies used to detect human serum albumin (HSA) is through the use of liquid crystals (LCs). The presence of HSA molecules disrupts the LCs supported on the AHSA-decorated slides thereby producing bright optical signals which are easily distinguishable.=using this assay can be as low as 15 ug/mL.^[12]

Alternatively the concentration of protein in the urine may be compared to the creatinine level in a spot urine sample. This is termed the protein/creatinine ratio (PCR). The 2005 UK Chronic Kidney Disease guidelines states PCR is a better test than 24 hour urinary protein measurement. Proteinuria is defined as a protein/creatinine ratio greater than 45 mg/mmol (which is equivalent to albumin/creatinine ratio of greater than 30 mg/mmol or approximately 300 mg/g) with very high levels of proteinuria being for a PCR greater than 100 mg/mmol.^[13]

Protein dipstick measurements should not be confused with the amount of protein detected on a test for microalbuminuria which denotes values for protein for urine in mg/day versus urine protein dipstick values which denote values for protein in mg/dL. That is, there is a basal level of proteinuria that can occur below 30 mg/day which is considered non-pathology. Values between 30–300 mg/day are termed microalbuminuria which is considered pathologic.^[14] Urine protein lab values for microalbumin of >30 mg/day correspond to a detection level within the "trace" to "1+" range of a urine dipstick protein assay. Therefore, positive indication of any protein detected on a urine dipstick assay obviates any need to perform a urine microalbumin test as the upper limit for microalbuminuria has already been exceeded.^[15]

Associated conditions[edit]

Proteinuria may be a sign of renal (kidney) damage. Since serum proteins are readily reabsorbed from urine, the presence of excess protein indicates either an insufficiency of absorption or impaired filtration. Diabetics may suffer from damaged nephrons and develop proteinuria. The most common cause of proteinuria is diabetes, and in any person with proteinuria and diabetes, the etiology of the underlying proteinuria should be separated into two categories: diabetic proteinuria versus the field.

With severe proteinuria, general hypoproteinemia can develop which results in diminished oncotic pressure. Symptoms of diminished oncotic pressure may include ascites, edema and hydrothorax.

Conditions with proteinuria as a sign[edit]

Proteinuria may be a feature of the following conditions:^[10]

Nephrotic syndromes (i.e. intrinsic renal failure)
Pre-eclampsia
Eclampsia
Toxic lesions of kidneys
Amyloidosis
Collagen vascular diseases (e.g. systemic lupus erythematosus)
Dehydration
Glomerular diseases, such as membranous glomerulonephritis, focal segmental glomerulonephritis, minimal change disease (lipoid nephrosis)
Strenuous exercise
Stress
Benign orthostatic (postural) proteinuria
Focal segmental glomerulosclerosis (FSGS)
IgA nephropathy (i.e. Berger's disease)
IgM nephropathy
Membranoproliferative glomerulonephritis
Membranous nephropathy
Minimal change disease
Sarcoidosis
Alport's syndrome
Diabetes mellitus (diabetic nephropathy)
Drugs (e.g. NSAIDs, nicotine, penicillamine, lithium carbonate, gold and other heavy metals, ACE inhibitors, antibiotics, or opiates (especially heroin)^[16]
Fabry's disease
Infections (e.g. HIV, syphilis, hepatitis, poststreptococcal infection, urinary schistosomiasis)
Aminoaciduria
Fanconi syndrome
Hypertensive nephrosclerosis
Interstitial nephritis
Sickle cell disease
Hemoglobinuria
Multiple myeloma
Myoglobinuria
Organ rejection: Kidney transplant patients may have gamma-globulins in their urine if the kidneys start to reject.^[17]
Ebola hemorrhagic fever
Nail patella syndrome
Familial Mediterranean fever
HELLP Syndrome
Systemic lupus erythematosus
Wegener's granulomatosis
Rheumatoid arthritis
Glycogen storage disease type 1^[18]
Goodpasture's syndrome
Henoch–Schönlein purpura
A urinary tract infection which has spread to the kidney(s)
Sjögren's syndrome
Post-infecious glumerulonephritis

This list is incomplete; you can help by expanding it.

Conditions with proteinuria consisting mainly of Bence-Jones proteins as a sign[edit]

Waldenstrom's macroglobulinemia
Chronic lymphocytic leukemia
Amyloidosis
Malignancies (e.g., lymphoma, other cancers)
Multiple myeloma

Treatment[edit]

Treating proteinuria mainly needs proper diagnosis of the cause. The most common cause is diabetic nephropathy; in this case, proper glycemic control may slow the progression. Medical management consists of angiotensin converting enzyme (ACE) inhibitors, which are typically first-line therapy for proteinuria. In patients whose proteinuria is not controlled with ACE inhibitors, the addition of an aldosterone antagonist (i.e., spironolactone)^[19] or angiotensin receptor blocker (ARB)^[20] may further reduce protein loss. Caution must be used if these agents are added to ACE inhibitor therapy due to the risk of hyperkalemia. Proteinuria secondary to autoimmune disease should be treated with steroids or steroid-sparing agent plus the use of ACE inhibitors.

References[edit]

^ ^a ^b ^c URINALYSIS Ed Friedlander, M.D., Pathologist - Retrieved 2007-01-20
^ foamy urine - Urology - MedHelp Retrieved 2007-01-20
^ Pneumaturia at GPnotebook Retrieved 2007-01-20
^ Clark, W. F.; Kortas, C.; Suri, R. S.; Moist, L. M.; Salvadori, M.; Weir, M. A.; Garg, A. X.; Wel, I. (2008). "Excessive fluid intake as a novel cause of proteinuria". Canadian Medical Association Journal 178 (2): 173–175. doi:10.1503/cmaj.070792. PMC 2175005. PMID 18195291.
^ "Drinking too much water called latest threat to health". Montreal Gazette. January 2008.
^ eMedicine > Proteinuria Author: Ronald J Kallen. Coauthor: Watson C Arnold. Updated: Apr 21, 2008
^ Ivanyi B, Kemeny E, Szederkenyi E, Marofka F, Szenohradszky P (December 2001). "The value of electron microscopy in the diagnosis of chronic renal allograft rejection". Mod. Pathol. 14 (12): 1200–8. doi:10.1038/modpathol.3880461. PMID 11743041. [1]
^ Simerville JA, Maxted WC, and Pahira JJ. Urinalysis: A Comprehensive Review Am Fam Physician. 2005 Mar 15;71(6):1153-1162. Accessed 2 Feb 2012.
^ http://medlib.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.html Retrieved 2007-01-20
^ ^a ^b Simerville JA, Maxted WC, Pahira JJ (2005). "Urinalysis: a comprehensive review". American Family Physician 71 (6): 1153–62. PMID 15791892.
^ http://www.answers.com/topic/protein-electrophoresis Retrieved 2007-01-20
^ Aliño, Vera Joanne R. and Yang, Kun-Lin (2011). "Using liquid crystals as a readout system in urinary albumin assays.". Analyst 20 (4): 893–900. doi:10.1039/c1an15143f. PMID 21709868.
^ "Identification, management and referral of adults with chronic kidney disease: concise guidelines" (PDF). UK Renal Association. 2005-09-27. - see Guideline 4 Confirmation of proteinuria, on page 9
^ "Urinary dipstick protein: a poor predictor of absent or severe proteinuria.". PMID 8296815. Am J Obstet Gynecol. 1994 Jan;170(1 Pt 1):137-41.
^ "The Urine Dipstick". Georgia Regents University.
^ Dettmeyer RB, Preuss J, Wollersen H, Madea B (2005). "Heroin-associated nephropathy". Expert opinion on drug safety 4 (1): 19–28. doi:10.1517/14740338.4.1.19. PMID 15709895.
^ Hermann G, Zühlke V, Faul P (1970). "Gamma globulin fragments in urine of kidney transplant patients in relation to rejection crisis". European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes 2 (1): 55–jjjkk63. PMID 4131420.
^ Janice Yang Chou, Dietrich Matern, Brian C. Mansfield, Yuan-Tsong Chen (2002). "Type 1 Glycogen Storage Diseases: Disorders of the Glucose-6-Phosphatase Complex". Current Molecular Medicine 2 (2): 121–143. doi:10.2174/1566524024605798. PMID 11949931.
^ Mehdi UF, Adams-Huet B, Raskin P, et al. (2009). "Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximum angiotensin-converting enzyme inhibition in diabetic nephropathy.". J Am Soc Nephrol 20 (12): 2641–50. doi:10.1681/ASN.2009070737. PMC 2794224. PMID 19926893.
^ Burgess E, Muirhead N, Rene de Cotret P, et al. (2009). "Supramaximal dose of candesartan in proteinuric renal disease.". J Am Soc Nephrol 20 (4): 893–900. doi:10.1681/ASN.2008040416. PMC 2663827. PMID 19211712.

UpToDate Contents

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1. 成人における尿蛋白排泄量の評価および非ネフローゼ域蛋白尿のみの評価 assessment of urinary protein excretion and evaluation of isolated non nephrotic proteinuria in adults
2. 小児における蛋白尿の評価 evaluation of proteinuria in children
3. 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
4. 小児におけるネフローゼ症候群の病因、臨床症状、および診断 etiology clinical manifestations and diagnosis of nephrotic syndrome in children
5. 妊娠中の蛋白尿の評価 evaluation of proteinuria in pregnancy

English Journal

The SLAM family member CD48 (Slamf2) protects lupus-prone mice from autoimmune nephritis.

Koh AE, Njoroge SW, Feliu M, Cook A, Selig MK, Latchman YE, Sharpe AH, Colvin RB, Paul E.SourceDivision of Pediatric Nephrology, Harvard Medical School and Massachusetts General Hospital, YAW-6C, 55 Fruit St., Boston, MA 02114, USA.
Journal of autoimmunity.J Autoimmun.2011 Aug;37(1):48-57. Epub 2011 May 10.
Polymorphisms in the SLAM family of leukocyte cell surface regulatory molecules have been associated with lupus-like phenotypes in both humans and mice. The murine Slamf gene cluster lies within the lupus-associated Sle1b region of mouse chromosome 1. Non-autoreactive C57BL/6 (B6) mice that have had
PMID 21561736

Clinical and histologic resolution of poststreptococcal glomerulonephritis with large subendothelial deposits and kidney failure.

Uchida T, Oda T, Watanabe A, Izumi T, Higashi K, Kushiyama T, Miura S, Kumagai H.SourceDepartment of Nephrology, National Defense Medical College, Tokorozawa, Saitama, Japan.
American journal of kidney diseases : the official journal of the National Kidney Foundation.Am J Kidney Dis.2011 Jul;58(1):113-7.
A 16-year-old male adolescent who had fallen and scratched his knee developed cold-like symptoms. Gross hematuria, oliguria, and peripheral edema appeared about 2 weeks after his fall. Tests showed hypocomplementemia, increased antistreptolysin O titers, and severe kidney failure with hematuria/prot
PMID 21684437

Japanese Journal

DNA Oxidation and Proteinuria Induced by Successive Triathlons Associated with Long-term Training: A Follow-up Case Study

安田従生,ボリンセレステ,カードゾペレッツファーナンド,ルビーブレント
環太平洋大学研究紀要 4, 109-120, 2011-03-01
… The purpose of this study was to determine alterations in whole body DNA oxidation and proteinuria induced by successive triathlons in addition to long-term training by the triathlete. … For all races, 24-hour urine output was collected on the day before (Pre) and after the race (Day 1) to evaluate exercise-induced proteinuria. … There were also similar patterns of proteinuria (total protein, albumin, N-acetyl-β-D-glucosaminidase, creatinine) at Pre and Day 1 in all four races (races A, B, C, and D). …
NAID 120003042192

蛋白尿(血尿を伴わない) (特集子どもの臨床検査--症候から診断・治療へ) -- (症候からみる臨床検査の進めかた)

高橋昌里
小児科診療 74(-) (879), 153-158, 2011
NAID 40018815392

Related Pictures

★リンクテーブル★

リンク元	「100Cases 59」「蛋白尿」「蛋白尿症」「proteinuric」「タンパク尿症」
拡張検索	「chance proteinuria」「idiopathic low molecular weight proteinuria」

「100Cases 59」

Proteinuria
ICD-10	R80
ICD-9	791.0
DiseasesDB	25320
eMedicine	med/94
MeSH	D011507

　　[★]

☆case59　尿中の血液

52歳　ビジネスマン

顕微鏡的血尿のため泌尿器科医に紹介があった。

主訴：顕微鏡的血尿

現病歴：6ヶ月前、new jofのためのisurance medicalで血尿を指摘された。以来、家庭医に2回血尿指摘された。以前の尿検査は正常だった。一度も顕微鏡は指摘されたことが無く、泌尿器系の症状もなかった。顕微鏡的血尿であることを除けば健康である。視覚、聴覚に問題なし。タバコ1日30本、アルコール35 unit/week(缶ビール(350ml)20本/週)

既往歴：特記無し。

家族歴：特記無し。腎臓病の家族歴無し

・身体所見

　栄養状態良く体調はよい。心拍：72/分、整。血圧：146/102 mmHg。心血管系、呼吸器系、腹部、神経学所見：異常なし。眼底鏡でarteriovenous nippingを認める。

・検査

(血液生化学)

　上昇：尿素、クレアチニン、γ-GTP

(尿検査)

蛋白：＋＋。血尿：＋＋。赤血球：>100 red cells

24時間尿蛋白：1.2g; 正常値 <200mg/24hr

(その他)

ECG：左室拡大。腎超音波検査：大きさは正常

(第一パラグラフ)

　・顕微鏡的血尿の原因は腎臓と尿路系のものがある(ex.前立腺病変、結石)。

　・顕微鏡的血尿　＋　高度のタンパク尿　＋　高血圧　＋　腎障害　＝　慢性糸球体腎炎の病態

　・γ-GTP 高値はアルコールの過剰摂取による肝臓病であることに適合する

　・男性で推奨されるアルコール摂取の上限は、28unit/週 ()

(第二パラグラフ)IgA 腎症

　・IgA 腎症は先進国における一般的な糸球体腎炎。メサンギウム領域におけるIgAの蓄積が特徴的

　・患者はしばしば、上気道感染と同時におこる顕微鏡血尿のエピソードがある

　・IgA 腎症は多くは特発性だけど、ヘノッホ-シェーンライン紫斑病(Henoch-Schonlein purpura)とアルコール性肝硬変(alcoholic cirrhosis)と関連するのが普通である。

　・IgA 腎症の患者の20%は20年の経過で末期腎不全(end-stage renal failure)に陥る。

(第三パラグラフ)基底膜病・アルポート症候群

　・菲薄基底膜病はisolated microscopic hematuria、minimal proteinuria及び正常腎機能(悪化しない)をしめす家族性の疾患である。

　・電顕的にはびまん性の糸球体基底膜の菲薄化が見られる(300-400nm -> 150-225nm)

　・アルポート症候群は進行性糸球体病態であり、聴覚消失と視覚異常と関連している。ふつうX連鎖優性遺伝で、男性がひどく影響を受ける。

(第四パラグラフ)What further incestigations would you organize?

　・腎生検

　・age>50: 尿細胞診、前立腺特異抗原、膀胱鏡　→　除外診断のため(膀胱・前立腺病変)

　・肝超音波検査が必要で、肝生検を考慮するべき。

(第五パラグラフ)What advice would you give this patient

　・指導：禁酒、血圧のコントロール

　・経過観察：透析、腎移植に移行しうるため

　・血清/血漿クレアチニン：これはGFRが50%減らないと上昇しない　→　この症例では軽度のクレアチニンの上昇は腎機能は正常の腎機能の40%であることを示す。

　・治療：免疫抑制薬がIgA 腎症の大部分で透析導入を遅らせるという証拠はない

■KEYPOINT

　・50歳以下の血尿のみを訴える患者はまず腎臓専門医に紹介すべき。

　・50歳以上の血尿のみを訴える患者は、膀胱や前立腺の疾患を除外するためにまず泌尿器科医に紹介すべき

　・血清/血漿クレアチニンのわずかな上昇は腎機能の大きな喪失を示している。

　・大量のアルコール摂取による肝障害は明らかな徴候なく起こるかもしれない。

■もっとも一般的な顕微鏡的血尿をきたす糸球体による原因

IgA 腎症

菲薄基底膜病(thin basement membrane disease)

アルポート症候群(XR)

■高血圧の病理的帰結 HIM.1552

・高血圧が生み出すリスクファクター：粥状硬化症

・高血圧が悪化因子？(predisposing factor)となる疾患：心不全、冠動脈疾患、梗塞、腎臓病、末梢動脈疾患

　心臓：高血圧性心疾患は高血圧に対する機能的・構造的適応　→　左心室肥大、拡張期機能不全(diastolic dysfunction)、うっ血性心不全、血行異常(冠状動脈の粥状硬化・微小血管障害による)、不整脈

　左心室肥大(1遺伝的要因と血行動態要因による)　→　↑リスク：冠動脈心疾患、梗塞、慢性心不全、突然死

　拡張期機能不全：(左心室壁が肥厚して拡張期に十分拡張できないという意味での機能不全(written by s))

　脳：(高血圧は脳梗塞と脳出血のリスクファクター)

　　・認知症(脳梗塞による)

　　・高血圧脳症(autoreguration(50-150mmHg)が傷害され、重度の頭痛、悪心・嘔吐、巣状神経徴候(focal neurologic sign)、精神状態の変調をきたす)

　腎臓：高血圧は腎障害と末期腎臓病のリスクファクター。

　　・腎臓における粥状硬化性の高血圧に関連した血管損傷は、最初に糸球体の前の細動脈に及ぶ。これにより糸球体と糸球体の後の構造に虚血性の変化を起こす。

　　・糸球体の損傷は糸球体の高灌流による糸球体毛細血管の損傷の結果かもしれない。

　　・糸球体の病理は糸球体硬化症を呈し、そして尿細管は虚血により萎縮する。

　末梢動脈：長期にわたって持続する高血圧により、下肢の動脈を狭窄させる　→　跛行

　網膜：交差現象(http://www.1stretinalscreen.com/ra_DR_NonDR.asp )

AV nipping is indicative of hypertension and describes the changes which occur at arteriovenous crossings in the retina where an artery crosses a vein. In patients with hypertension and associated arteriolosclerosis (narrowing of the artery) the artery applies increased pressure on the vein at the point where it passes over the top of the vein.

■顕微鏡的血尿

　血尿のうち、肉眼的には血尿ではないが、尿沈渣で400倍毎視野1個以上の赤血球を認める場合をいう。しかしそれでは再現性に乏しいので、一般的には5個以上の赤血球を認める場合を顕微鏡的血尿といい病的意義をもつ。

■glossary

modest adj. 謙虚な。慎み深い、控えめな、遠慮がちの。(主に女性が)しとやかにした、ひどく上品な。質素な、地味な。適度の、穏当な。大きくない、ささやかな。

「蛋白尿」

　　[★]

英: proteinuria
同: タンパク尿
関: 尿、タンパク尿症、蛋白尿症; (臨床検査)尿蛋白

定義

蛋白質の尿中排泄量が150 mg/日(4mg/時/m2)を超えた尿　⇔　健常者 10-100 mg/日

ネフローゼ症候群は1日3.5g以上のタンパク尿で疑われる
妊娠高血圧腎症は1日300mg～2gで軽症、2g以上で重症と判定される。

分類

疾患と部位

IMD.162

腎前性		多発性骨髄腫、横紋筋融解症、不適合輸血
腎性	糸球体性	急性腎炎、慢性腎炎、ネフローゼ症候群、糖尿病性腎症、全身性エリテマトーデス、アミロイドーシス、腎硬化症
	尿細管性	Fanconi症候群、急性尿細管壊死、慢性腎孟腎炎、痛風腎、重金属中毒、アミノグリコシド系抗菌薬、間質性腎炎
腎後性		尿路感染症、尿路結石症、尿路系腫瘍