臨床検査57巻6号

2013年06月発行

今月の特集1 尿バイオマーカー

Neutrophil gelatinase-associated lipocalinによる病態解析

著者： 森潔¹ 桒原孝成² 横井秀基² 笠原正登² 向山政志² 中尾一和²

所属機関： ¹京都大学大学院医学研究科メディカルイノベーションセンター・TMKプロジェクト ²京都大学大学院医学研究科内分泌代謝内科

ページ範囲：P.617 - P.622

■尿中Ngalは重症の急性腎障害を超早期に診断することを可能とするバイオマーカーである．

■尿中Ngalは糸球体・近位尿細管・遠位ネフロンのいずれの障害・機能不全でも上昇する．

■尿中Ngalは慢性腎臓病の病勢，予後，治療薬の効果を判定するのに有用である．

参考文献

1）Mori K, Nakao K：Neutrophil gelatinase-associated lipocalin as the real-time indicator of active kidney damage. Kidney Int　71：967-970，2007

2）Flower DR, North AC, Sansom CE：The lipocalin protein family: structural and sequence overview. Biochim Biophys Acta　1482：9-24，2000

3）Mori K, Lee HT, Rapoport D, et al：Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest　115：610-621，2005

4）Hvidberg V, Jacobsen C, Strong RK, et al：The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett　579：773-777，2005

5）Yang J, Goetz D, Li JY, et al：An iron delivery pathway mediated by a lipocalin. Mol Cell　10：1045-1056，2002

6）Goetz DH, Holmes MA, Borregaard N, et al：The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell　10：1033-1043，2002

7）森潔，向山政志，中尾一和：微生物の鉄捕捉分子と生体の防御機構．日本内科学会雑誌　99：1188-1193，2010

8）Flo TH, Smith KD, Sato S, et al：Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature　432：917-921，2004

9）Barasch J, Mori K：Cell biology: iron thievery. Nature　432：811-813，2004

10）Bao G, Clifton M, Hoette TM, et al：Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nat Chem Biol　6：602-609，2010

11）森潔，向山政志，中尾一和：多彩な生命現象に関わる鉄結合性小化合物siderophoreの意義．細胞工学　27：226-230，2008

12）森潔，向山政志，中尾一和：siderophore結合蛋白の生物学　分化誘導，組織障害，癌，感染，造血の新しい接点．臨床血液　50：519-526，2009

13）Mori K, Yang J, Barasch J：Ureteric bud controls multiple steps in the conversion of mesenchyme to epithelia. Semin Cell Dev Biol　14：209-216，2003

14）Hanai J, Mammoto T, Seth P, et al：Lipocalin 2 diminishes invasiveness and metastasis of Ras-transformed cells. J Biol Chem　280：13641-13647，2005

15）Devireddy LR, Teodoro JG, Richard FA, et al：Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Science　293：829-834，2001

16）Devireddy LR, Gazin C, Zhu X, et al：A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell　123：1293-1305，2005

17）Lee S, Lee J, Kim S, et al：A dual role of lipocalin 2 in the apoptosis and deramification of activated microglia. J Immunol　179：3231-3241，2007

18）Miharada K, Hiroyama T, Sudo K, et al：Lipocalin 2-mediated growth suppression is evident in human erythroid and monocyte/macrophage lineage cells. J Cell Physiol　215：526-537，2008

19）Cowland JB, Muta T, Borregaard N：IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta. J Immunol　176：5559-5566，2006

20）Kuwabara T, Mori K, Mukoyama M, et al：Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney Int　75：285-294，2009

21）Paragas N, Qiu A, Zhang Q, et al：The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat Med　17：216-222，2011

22）森潔，向山政志，桒原孝成，他：CKDにおける新規バイオマーカーNgalの意義．日本臨牀　67：1233-1241，2009

23）Nickolas TL, Forster CS, Sise ME, et al：NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease. Kidney Int　82：718-722，2012

24）Mishra J, Dent C, Tarabishi R, et al：Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet　365：1231-1238，2005

25）Wagener G, Jan M, Kim M, et al：Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology　105：485-491，2006

26）Nickolas TL, O’Rourke MJ, Yan J, et al：Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med　148：810-819，2008

27）Singer E, Elger A, Elitok S, et al：Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney Int　80：405-414，2011

28）McIlroy DR, Wagener G, Lee HT：Neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery: the effect of baseline renal function on diagnostic performance. Clin J Am Soc Nephrol　5：211-219，2010

29）Bolignano D, Lacquaniti A, Coppolino G, et al：Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol　4：337-344，2009

30）Smith ER, Lee D, Cai MM, et al：Urinary neutrophil gelatinase-associated lipocalin may aid prediction of renal decline in patients with non-proteinuric Stages 3 and 4 chronic kidney disease (CKD). Nephrol Dial Transplant, in press

31）Liu KD, Yang W, Anderson AH, et al：Urine neutrophil gelatinase-associated lipocalin levels do not improve risk prediction of progressive chronic kidney disease. Kidney Int, in press

32）Kasahara M, Mori K, Satoh N, et al：Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients. Nephrol Dial Transplant　24：2608-2609，2009

33）Devarajan P：Neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology (Carlton)　15：419-428，2010

34）Ichimura T, Bonventre JV, Bailly V, et al：Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem　273：4135-4142，1998

35）Coca SG, Yalavarthy R, Concato J, et al：Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int　73：1008-1016，2008

36）Vaidya VS, Ozer JS, Dieterle F, et al：Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol　28：478-485，2010

37）Vanmassenhove J, Vanholder R, Nagler E, et al：Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature. Nephrol Dial Transplant　28：254-273，2013