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The Application of Urinary Proteomics for the Detection of Biomarkers of Kidney Diseases

  • Song Jiang
  • Yu Wang
  • Zhihong LiuEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 845)

Abstract

Urine is a biological material that can be easily obtained in the clinic. The identification of proteins excreted in urine provides useful biological information about the kidney as well as a unique opportunity to examine physiological and pathological changes in the kidney in a noninvasive manner. Recent technological advances in urinary proteomic profiling have provided the foundation for a number of urinary proteomic studies directed at identifying markers of kidney disease diagnosis, prognosis, or responsiveness to therapy. In this review, we describe the strengths of different urinary proteomic methods for the discovery of potential biomarkers of kidney diseases. We also highlight the limitations and future goals of these approaches.

Keywords

Urinary proteomics Biomarker Kidney diseases 

References

  1. 1.
    Adachi J, Kumar C, Zhang Y, Olsen JV, Mann M (2006) The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins. Genome Biol 7:R80PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Alkhalaf A, Zurbig P, Bakker SJ, Bilo HJ, Cerna M, Fischer C, Fuchs S, Janssen B, Medek K, Mischak H, Roob JM, Rossing K, Rossing P, Rychlik I, Sourij H, Tiran B, Winklhofer-Roob BM, Navis GJ, Group P (2010) Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy. PloS ONE 5: e13421Google Scholar
  3. 3.
    Aregger F, Pilop C, Uehlinger DE, Brunisholz R, Carrel TP, Frey FJ, Frey BM (2010) Urinary proteomics before and after extracorporeal circulation in patients with and without acute kidney injury. J Thoracic Cardiovasc Surg 139:692–700CrossRefGoogle Scholar
  4. 4.
    Aregger F, Uehlinger DE, Witowski J, Brunisholz RA, Hunziker P, Frey FJ, Jorres A (2014) Identification of IGFBP-7 by urinary proteomics as a novel prognostic marker in early acute kidney injury. Kidney Int 85:909–919PubMedCrossRefGoogle Scholar
  5. 5.
    Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ (2009) M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. New England J Med 361:11–21CrossRefGoogle Scholar
  6. 6.
    Beck LH Jr, Fervenza FC, Beck DM, Bonegio RG, Malik FA, Erickson SB, Cosio FG, Cattran DC, Salant DJ (2011) Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol JASN 22:1543–1550CrossRefGoogle Scholar
  7. 7.
    Cameron JS (1999) Lupus nephritis. J Am Soc Nephrol JASN 10:413–424Google Scholar
  8. 8.
    Cravedi P, Ruggenenti P, Remuzzi G (2011) Circulating anti-PLA2R autoantibodies to monitor immunological activity in membranous nephropathy. J Am Soc Nephrol JASN 22:1400–1402CrossRefGoogle Scholar
  9. 9.
    D’Agati V (2003) Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol 23:117–134PubMedCrossRefGoogle Scholar
  10. 10.
    D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. New England J Med 365:2398–2411CrossRefGoogle Scholar
  11. 11.
    Deen WM, Bridges CR, Brenner BM, Myers BD (1985) Heteroporous model of glomerular size selectivity: application to normal and nephrotic humans. Am J Physiol 249:F374–F389PubMedGoogle Scholar
  12. 12.
    Devarajan P (2007) Proteomics for biomarker discovery in acute kidney injury. Semin Nephrol 27:637–651PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Giorgino F, Laviola L, Cavallo Perin P, Solnica B, Fuller J, Chaturvedi N (2004) Factors associated with progression to macroalbuminuria in microalbuminuric Type 1 diabetic patients: the EURODIAB prospective complications study. Diabetologia 47:1020–1028PubMedCrossRefGoogle Scholar
  14. 14.
    Good DM, Zurbig P, Argiles A, Bauer HW, Behrens G, Coon JJ, Dakna M, Decramer S, Delles C, Dominiczak AF, Ehrich JH, Eitner F, Fliser D, Frommberger M, Ganser A, Girolami MA, Golovko I, Gwinner W, Haubitz M, Herget-Rosenthal S, Jankowski J, Jahn H, Jerums G, Julian BA, Kellmann M, Kliem V, Kolch W, Krolewski AS, Luppi M, Massy Z, Melter M, Neususs C, Novak J, Peter K, Rossing K, Rupprecht H, Schanstra JP, Schiffer E, Stolzenburg JU, Tarnow L, Theodorescu D, Thongboonkerd V, Vanholder R, Weissinger EM, Mischak H, Schmitt-Kopplin P (2010) Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease. Mol Cel Proteomics MCP 9:2424–2437CrossRefGoogle Scholar
  15. 15.
    He Q, Shao L, Yu J, Ji S, Wang H, Mao Y, Chen J (2012) Urinary proteome analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with magnetic beads for identifying the pathologic presentation of clinical early IgA nephropathy. J Biomed Nanotechnol 8:133–139PubMedCrossRefGoogle Scholar
  16. 16.
    Ho J, Lucy M, Krokhin O, Hayglass K, Pascoe E, Darroch G, Rush D, Nickerson P, Rigatto C, Reslerova M (2009) Mass spectrometry-based proteomic analysis of urine in acute kidney injury following cardiopulmonary bypass: a nested case-control study. Am J Kidney Dis Official J Nat Kidney Found 53:584–595CrossRefGoogle Scholar
  17. 17.
    Ho J, Reslerova M, Gali B, Gao A, Bestland J, Rush DN, Nickerson PW, Rigatto C (2011) Urinary hepcidin-25 and risk of acute kidney injury following cardiopulmonary bypass. Clin J Am Soc Nephrol CJASN 6:2340–2346CrossRefGoogle Scholar
  18. 18.
    Jin J, Ku YH, Kim Y, Kim Y, Kim K, Lee JY, Cho YM, Lee HK, Park KS, Kim Y (2012) Differential proteome profiling using iTRAQ in microalbuminuric and normoalbuminuric type 2 diabetic patients. Exp Diab Res 2012:168602CrossRefGoogle Scholar
  19. 19.
    Kerjaschki D, Farquhar MG (1982) The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci USA 79:5557–5561PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Kitiyakara C, Kopp JB, Eggers P (2003) Trends in the epidemiology of focal segmental glomerulosclerosis. Semin Nephrol 23:172–182PubMedCrossRefGoogle Scholar
  21. 21.
    Knight EL, Verhave JC, Spiegelman D, Hillege HL, de Zeeuw D, Curhan GC, de Jong PE (2004) Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int 65:1416–1421PubMedCrossRefGoogle Scholar
  22. 22.
    Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfels AB, Wolfe RA, Jones E, Disney AP, Briggs D, McCredie M, Boyle P (2000) Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study. Am J Kidney Dis Official J National Kidney Found 35:157–165CrossRefGoogle Scholar
  23. 23.
    Merchant ML, Perkins BA, Boratyn GM, Ficociello LH, Wilkey DW, Barati MT, Bertram CC, Page GP, Rovin BH, Warram JH, Krolewski AS, Klein JB (2009) Urinary peptidome may predict renal function decline in type 1 diabetes and microalbuminuria. J Am Soc Nephrol JASN 20:2065–2074CrossRefGoogle Scholar
  24. 24.
    Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol JASN 14:2534–2543CrossRefGoogle Scholar
  25. 25.
    Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P (2004) Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 24:307–315PubMedCrossRefGoogle Scholar
  26. 26.
    Ngai HH, Sit WH, Jiang PP, Xu RJ, Wan JM, Thongboonkerd V (2006) Serial changes in urinary proteome profile of membranous nephropathy: implications for pathophysiology and biomarker discovery. J Proteome Res 5:3038–3047PubMedCrossRefGoogle Scholar
  27. 27.
    Park MR, Wang EH, Jin DC, Cha JH, Lee KH, Yang CW, Kang CS, Choi YJ (2006) Establishment of a 2-D human urinary proteomic map in IgA nephropathy. Proteomics 6:1066–1076PubMedCrossRefGoogle Scholar
  28. 28.
    Perkins BA, Krolewski AS (2005) Early nephropathy in type 1 diabetes: a new perspective on who will and who will not progress. Curr Diab Rep 5:455–463PubMedCrossRefGoogle Scholar
  29. 29.
    Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS (2003) Regression of microalbuminuria in type 1 diabetes. New England J Med 348:2285–2293CrossRefGoogle Scholar
  30. 30.
    Perkins BA, Nelson RG, Ostrander BE, Blouch KL, Krolewski AS, Myers BD, Warram JH (2005) Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study. J Am Soc Nephrol JASN 16:1404–1412CrossRefGoogle Scholar
  31. 31.
    Perkins BA, Ficociello LH, Ostrander BE, Silva KH, Weinberg J, Warram JH, Krolewski AS (2007) Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes. J Am Soc Nephrol JASN 18:1353–1361CrossRefGoogle Scholar
  32. 32.
    Pieper R, Gatlin CL, McGrath AM, Makusky AJ, Mondal M, Seonarain M, Field E, Schatz CR, Estock MA, Ahmed N, Anderson NG, Steiner S (2004) Characterization of the human urinary proteome: a method for high-resolution display of urinary proteins on two-dimensional electrophoresis gels with a yield of nearly 1400 distinct protein spots. Proteomics 4:1159–1174PubMedCrossRefGoogle Scholar
  33. 33.
    Pisitkun T, Johnstone R, Knepper MA (2006) Discovery of urinary biomarkers. Mol Cell Proteomics MCP 5:1760–1771CrossRefGoogle Scholar
  34. 34.
    Piyaphanee N, Ma Q, Kremen O, Czech K, Greis K, Mitsnefes M, Devarajan P, Bennett MR (2011) Discovery and initial validation of alpha 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome. Proteomics Clin Appl 5:334–342PubMedCrossRefGoogle Scholar
  35. 35.
    Qin W, Beck LH Jr, Zeng C, Chen Z, Li S, Zuo K, Salant DJ, Liu Z (2011) Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol JASN 22:1137–1143CrossRefGoogle Scholar
  36. 36.
    Rocchetti MT, Centra M, Papale M, Bortone G, Palermo C, Centonze D, Ranieri E, Di Paolo S, Gesualdo L (2008) Urine protein profile of IgA nephropathy patients may predict the response to ACE-inhibitor therapy. Proteomics 8:206–216PubMedCrossRefGoogle Scholar
  37. 37.
    Rossing P (2005) The changing epidemiology of diabetic microangiopathy in type 1 diabetes. Diabetologia 48:1439–1444PubMedCrossRefGoogle Scholar
  38. 38.
    Rossing K, Mischak H, Dakna M, Zurbig P, Novak J, Julian BA, Good DM, Coon JJ, Tarnow L, Rossing P, Network P (2008) Urinary proteomics in diabetes and CKD. J Am Soc Nephrol (JASN) 19:1283–1290CrossRefGoogle Scholar
  39. 39.
    Shemesh O, Ross JC, Deen WM, Grant GW, Myers BD (1986) Nature of the glomerular capillary injury in human membranous glomerulopathy. J Clin Investig 77:868–877PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Somparn P, Hirankarn N, Leelahavanichkul A, Khovidhunkit W, Thongboonkerd V, Avihingsanon Y (2012) Urinary proteomics revealed prostaglandin H(2)D-isomerase, not Zn-alpha2-glycoprotein, as a biomarker for active lupus nephritis. J Proteomics 75:3240–3247PubMedCrossRefGoogle Scholar
  41. 41.
    Surin B, Sachon E, Rougier JP, Steverlynck C, Garreau C, Lelongt B, Ronco P, Piedagnel R (2013) LG3 fragment of endorepellin is a possible biomarker of severity in IgA nephropathy. Proteomics 13:142–152PubMedCrossRefGoogle Scholar
  42. 42.
    Suzuki M, Ross GF, Wiers K, Nelson S, Bennett M, Passo MH, Devarajan P, Brunner HI (2007) Identification of a urinary proteomic signature for lupus nephritis in children. Pediatric Nephrol 22:2047–2057CrossRefGoogle Scholar
  43. 43.
    Thomas DB, Franceschini N, Hogan SL, Ten Holder S, Jennette CE, Falk RJ, Jennette JC (2006) Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 69:920–926PubMedCrossRefGoogle Scholar
  44. 44.
    Varghese SA, Powell TB, Budisavljevic MN, Oates JC, Raymond JR, Almeida JS, Arthur JM (2007) Urine biomarkers predict the cause of glomerular disease. J Am Soc Nephrol (JASN) 18:913–922CrossRefGoogle Scholar
  45. 45.
    Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT (2006) Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 105:485–491PubMedCrossRefGoogle Scholar
  46. 46.
    Waikar SS, Curhan GC, Wald R, McCarthy EP, Chertow GM (2006) Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol (JASN) 17:1143–1150CrossRefGoogle Scholar
  47. 47.
    Wang L, Hong Q, Lv Y, Feng Z, Zhang X, Wu L, Cui S, Hou K, Su H, Huang Z, Wu D, Chen X (2012) Autophagy can repair endoplasmic reticulum stress damage of the passive Heymann nephritis model as revealed by proteomics analysis. J Proteomics 75:3866–3876PubMedCrossRefGoogle Scholar
  48. 48.
    Wu T, Du Y, Han J, Singh S, Xie C, Guo Y, Zhou XJ, Ahn C, Saxena R, Mohan C (2013) Urinary angiostatin–a novel putative marker of renal pathology chronicity in lupus nephritis. Mol Cell Proteomics (MCP) 12:1170–1179CrossRefGoogle Scholar
  49. 49.
    Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, Molitoris BA, Himmelfarb J, Collins AJ (2006) Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol (JASN) 17:1135–1142CrossRefGoogle Scholar
  50. 50.
    Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J, China National D, Metabolic Disorders Study G (2010) Prevalence of diabetes among men and women in China. New England J Med 362: 1090–1101Google Scholar
  51. 51.
    Ympa YP, Sakr Y, Reinhart K, Vincent JL (2005) Has mortality from acute renal failure decreased? A systematic review of the literature. Am J Med 118:827–832PubMedCrossRefGoogle Scholar
  52. 52.
    Yokota H, Hiramoto M, Okada H, Kanno Y, Yuri M, Morita S, Naitou M, Ichikawa A, Katoh M, Suzuki H (2007) Absence of increased alpha1-microglobulin in IgA nephropathy proteinuria. Mol Cell Proteomics (MCP) 6:738–744CrossRefGoogle Scholar
  53. 53.
    Zhang X, Jin M, Wu H, Nadasdy T, Nadasdy G, Harris N, Green-Church K, Nagaraja H, Birmingham DJ, Yu CY, Hebert LA, Rovin BH (2008) Biomarkers of lupus nephritis determined by serial urine proteomics. Kidney Int 74:799–807PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.National Kidney Disease Clinical Research Center, Jinling HospitalNanjing University School of MedicineNanjingChina

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