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Published in:

01-05-2015 | Review

Proteomic urinary biomarker approach in renal disease: from discovery to implementation

Authors: Joost P. Schanstra, Harald Mischak

Published in: Pediatric Nephrology | Issue 5/2015

Abstract

Biomarkers hold the promise of significantly improving health care by enabling prognosis and diagnosis with improved accuracy, and at earlier points in time. Previous results have indicated that single biomarkers are not suitable to describe complex diseases such as kidney disease. Here we provide an update on the progress of urinary proteomics-based studies and strategies to develop biomarker-based classifiers that tolerate instability and inconsistency of individual biomarkers. The examples focus on two major fields in nephrology: chronic kidney disease in the adult population and obstructive nephropathies in the pediatric population. When employed adequately, urinary proteomics demonstrates a clear value in kidney disease, indicating that the current status quo ruling for decades now could be changed by applying modern “omics” approaches. However, while research is able to deliver these useful tools for patient management, the issues associated with implementation are not yet solved. Active engagement of the relevant clinical professional societies, as well as patient’s organizations, might help to implement these omics approaches that have shown a clear benefit for the patient.

Lambers Heerspink HJ, de Zeeuw D (2010) Debate: PRO position. Should microalbuminuria ever be considered as a renal endpoint in any clinical trial? Am J Nephrol 31:458–461, discussion 468CrossRefPubMed

Glassock RJ (2010) Debate: CON position. Should microalbuminuria ever be considered as a renal endpoint in any clinical trial? Am J Nephrol 31:462–465, discussion 466–467CrossRefPubMed

Perkins BA, Ficociello LH, Roshan B, Warram JH, Krolewski AS (2010) In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria. Kidney Int 77:57–64CrossRefPubMedCentralPubMed

Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, Investigators RS (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869CrossRefPubMed

Morris RK, Malin GL, Khan KS, Kilby MD (2009) Antenatal ultrasound to predict postnatal renal function in congenital lower urinary tract obstruction: systematic review of test accuracy. BJOG 116:1290–1299CrossRefPubMed

Morris RK, Quinlan-Jones E, Kilby MD, Khan KS (2007) Systematic review of accuracy of fetal urine analysis to predict poor postnatal renal function in cases of congenital urinary tract obstruction. Prenat Diagn 27:900–911CrossRefPubMed

Rosell R, Bivona TG, Karachaliou N (2013) Genetics and biomarkers in personalisation of lung cancer treatment. Lancet 382:720–731CrossRefPubMed

Decramer S, Parant O, Beaufils S, Clauin S, Guillou C, Kessler S, Aziza J, Bandin F, Schanstra JP, Bellanne-Chantelot C (2007) Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol 18:923–933CrossRefPubMed

Faguer S, Decramer S, Chassaing N, Bellanne-Chantelot C, Calvas P, Beaufils S, Bessenay L, Lengele JP, Dahan K, Ronco P, Devuyst O, Chauveau D (2011) Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood. Kidney Int 80:768–776CrossRefPubMed

10.

Heidet L, Decramer S, Pawtowski A, Moriniere V, Bandin F, Knebelmann B, Lebre AS, Faguer S, Guigonis V, Antignac C, Salomon R (2010) Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol 5:1079–1090CrossRefPubMedCentralPubMed

11.

Harris PC, Rossetti S (2010) Determinants of renal disease variability in ADPKD. Adv Chronic Kidney Dis 17:131–139CrossRefPubMedCentralPubMed

12.

Suthanthiran M, Schwartz JE, Ding R, Abecassis M, Dadhania D, Samstein B, Knechtle SJ, Friedewald J, Becker YT, Sharma VK, Williams NM, Chang CS, Hoang C, Muthukumar T, August P, Keslar KS, Fairchild RL, Hricik DE, Heeger PS, Han L, Liu J, Riggs M, Ikle DN, Bridges ND, Shaked A, Clinical Trials in Organ Transplantation 04 Study I (2013) Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med 369:20–31CrossRef

13.

Guo Y, Xiao P, Lei S, Deng F, Xiao GG, Liu Y, Chen X, Li L, Wu S, Chen Y, Jiang H, Tan L, Xie J, Zhu X, Liang S, Deng H (2008) How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochimica Biophysica Sin 40:426–436CrossRef

14.

Soufi B, Kelstrup CD, Stoehr G, Frohlich F, Walther TC, Olsen JV (2009) Global analysis of the yeast osmotic stress response by quantitative proteomics. Mol Biosyst 5:1337–1346CrossRefPubMed

15.

Decramer S, Gonzalez de Peredo A, Breuil B, Mischak H, Monsarrat B, Bascands JL, Schanstra JP (2008) Urine in clinical proteomics. Mol Cell Proteomics 7:1850–1862CrossRefPubMed

16.

Winnike JH, Busby MG, Watkins PB, O’Connell TM (2009) Effects of a prolonged standardized diet on normalizing the human metabolome. Am J Clin Nutr 90:1496–1501CrossRefPubMedCentralPubMed

17.

Heinzmann SS, Merrifield CA, Rezzi S, Kochhar S, Lindon JC, Holmes E, Nicholson JK (2012) Stability and robustness of human metabolic phenotypes in response to sequential food challenges. J Proteome Res 11:643–655CrossRefPubMed

18.

Caubet C, Lacroix C, Decramer S, Drube J, Ehrich JH, Mischak H, Bascands JL, Schanstra JP (2010) Advances in urinary proteome analysis and biomarker discovery in pediatric renal disease. Pediatr Nephrol 25:27–35CrossRefPubMed

19.

Thongboonkerd V, Malasit P (2005) Renal and urinary proteomics: current applications and challenges. Proteomics 5:1033–1042CrossRefPubMed

20.

Schiffer E, Mischak H, Novak J (2006) High resolution proteome/peptidome analysis of body fluids by capillary electrophoresis coupled with MS. Proteomics 6:5615–5627CrossRefPubMed

21.

Rifai N, Gillette MA, Carr SA (2006) Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 24:971–983CrossRefPubMed

22.

Mischak H, Allmaier G, Apweiler R, Attwood T, Baumann M, Benigni A, Bennett SE, Bischoff R, Bongcam-Rudloff E, Capasso G, Coon JJ, D’Haese P, Dominiczak AF, Dakna M, Dihazi H, Ehrich JH, Fernandez-Llama P, Fliser D, Frokiaer J, Garin J, Girolami M, Hancock WS, Haubitz M, Hochstrasser D, Holman RR, Ioannidis JP, Jankowski J, Julian BA, Klein JB, Kolch W, Luider T, Massy Z, Mattes WB, Molina F, Monsarrat B, Novak J, Peter K, Rossing P, Sanchez-Carbayo M, Schanstra JP, Semmes OJ, Spasovski G, Theodorescu D, Thongboonkerd V, Vanholder R, Veenstra TD, Weissinger E, Yamamoto T, Vlahou A (2010) Recommendations for biomarker identification and qualification in clinical proteomics. Sci Transl Med 2(46):42CrossRef

23.

Mischak H, Ioannidis JP, Argiles A, Attwood TK, Bongcam-Rudloff E, Broenstrup M, Charonis A, Chrousos GP, Delles C, Dominiczak A, Dylag T, Ehrich J, Egido J, Findeisen P, Jankowski J, Johnson RW, Julien BA, Lankisch T, Leung HY, Maahs D, Magni F, Manns MP, Manolis E, Mayer G, Navis G, Novak J, Ortiz A, Persson F, Peter K, Riese HH, Rossing P, Sattar N, Spasovski G, Thongboonkerd V, Vanholder R, Schanstra JP, Vlahou A (2012) Implementation of proteomic biomarkers: making it work. Eur J Clin Invest 42:1027–1036CrossRefPubMedCentralPubMed

24.

Dakna M, Harris K, Kalousis A, Carpentier S, Kolch W, Schanstra JP, Haubitz M, Vlahou A, Mischak H, Girolami M (2010) Addressing the challenge of defining valid proteomic biomarkers and classifiers. BMC Bioinforma 11:594CrossRef

25.

Cairns DA, Barrett JH, Billingham LJ, Stanley AJ, Xinarianos G, Field JK, Johnson PJ, Selby PJ, Banks RE (2009) Sample size determination in clinical proteomic profiling experiments using mass spectrometry for class comparison. Proteomics 9:74–86CrossRefPubMed

26.

Eckardt KU, Coresh J, Devuyst O, Johnson RJ, Kottgen A, Levey AS, Levin A (2013) Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 382:158–169CrossRefPubMed

27.

Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382:260–272CrossRefPubMed

28.

Galle J (2008) Reduction of proteinuria with angiotensin receptor blockers. Nat Clin Pract Cardiovasc Med, Suppl 1:S36–S43CrossRef

29.

Turner JM, Bauer C, Abramowitz MK, Melamed ML, Hostetter TH (2012) Treatment of chronic kidney disease. Kidney Int 81:351–362CrossRefPubMed

30.

Devarajan P (2010) Review: neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology 15:419–428CrossRefPubMed

31.

Nickolas TL, Forster CS, Sise ME, Barasch N, Valle DS, Viltard M, Buchen C, Kupferman S, Carnevali ML, Bennett M, Mattei S, Bovino A, Argentiero L, Magnano A, Devarajan P, Mori K, Erdjument-Bromage H, Tempst P, Allegri L, Barasch J (2012) NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease. Kidney Int 82:718–722CrossRefPubMedCentralPubMed

32.

Liu KD, Yang W, Anderson AH, Feldman HI, Demirjian S, Hamano T, He J, Lash J, Lustigova E, Rosas SE, Simonson MS, Tao K, Hsu CY, Chronic Renal Insufficiency Cohort study investigators (2013) Urine neutrophil gelatinase-associated lipocalin levels do not improve risk prediction of progressive chronic kidney disease. Kidney Int 83:909–914

33.

Chou KM, Lee CC, Chen CH, Sun CY (2013) Clinical value of NGAL, L-FABP and albuminuria in predicting GFR decline in type 2 diabetes mellitus patients. PloS One 8:e54863CrossRefPubMedCentralPubMed

34.

Rau S, Habicht A, Kauke T, Hillmer A, Wessely M, Stangl M, Guba M, Fischereder M, Schonermarck U (2013) Neutrophil gelatinase-associated lipocalin and end-stage renal disease: it is not all about the kidneys! Eur J Clin Invest 43:816–820CrossRefPubMed

35.

Andrassy KM (2013) Comments on ’KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease’. Kidney Int 84:622–623CrossRefPubMed

36.

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 Cell Proteomics 9:2424–2437CrossRefPubMedCentralPubMed

37.

Andersen S, Mischak H, Zurbig P, Parving HH, Rossing P (2010) Urinary proteome analysis enables assessment of renoprotective treatment in type 2 diabetic patients with microalbuminuria. BMC Nephrol 11:29CrossRefPubMedCentralPubMed

38.

Siwy J, Schanstra JP, Argiles A, Bakker SJL, Beige J, Boucek P, Brand K, Delles C, Duranton F, Fernandez-Fernandez B, Jankowski M-L, Al Khatib M, Kunt T, Lajer M, Lichtinghagen R, Lindhardt M, Maahs DM, Mischak H, Mullen W, Navis G, Noutson M, Ortiz A, Persson F, Petrie JR, Roob JM, Rossing P, Ruggenenti P, Rychlik I, Serra AL, Snell-Bergeon J, Spasovski G, von der Leyen H, Winklhofer-Roob BM, Zürbig P, Jankowski J (2014) Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy. Nephrol Dial Transplant. doi:10.1093/ndt/gfu039

39.

Molin L, Seraglia R, Lapolla A, Ragazzi E, Gonzalez J, Vlahou A, Schanstra JP, Albalat A, Dakna M, Siwy J, Jankowski J, Bitsika V, Mischak H, Zurbig P, Traldi P (2012) A comparison between MALDI-MS and CE-MS data for biomarker assessment in chronic kidney diseases. J Proteomics 75:5888–5897CrossRefPubMed

40.

Zurbig P, Jerums G, Hovind P, Macisaac RJ, Mischak H, Nielsen SE, Panagiotopoulos S, Persson F, Rossing P (2012) Urinary proteomics for early diagnosis in diabetic nephropathy. Diabetes 61:3304–3313CrossRefPubMedCentralPubMed

41.

Roscioni SS, de Zeeuw D, Hellemons ME, Mischak H, Zurbig P, Bakker SJ, Gansevoort RT, Reinhard H, Persson F, Lajer M, Rossing P, Lambers Heerspink HJ (2013) A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus. Diabetologia 56:259–267CrossRefPubMed

42.

Argiles A, Siwy J, Duranton F, Gayrard N, Dakna M, Lundin U, Osaba L, Delles C, Mourad G, Weinberger KM, Mischak H (2013) CKD273, a new proteomics classifier assessing CKD and its prognosis. PloS One 8:e62837CrossRefPubMedCentralPubMed

43.

Mischak H, Schanstra JP (2011) CE-MS in biomarker discovery, validation, and clinical application. Proteomics Clin Appl 5:9–23CrossRefPubMed

44.

Mischak H, Delles C, Klein J, Schanstra JP (2010) Urinary proteomics based on capillary electrophoresis-coupled mass spectrometry in kidney disease: discovery and validation of biomarkers, and clinical application. Adv Chronic Kidney Dis 17:493–506CrossRefPubMed

45.

Metzger J, Schanstra JP, Mischak H (2009) Capillary electrophoresis-mass spectrometry in urinary proteome analysis: current applications and future developments. Anal Bioanal Chem 393:1431–1442CrossRefPubMed

46.

Mischak H, Vlahou A, Ioannidis JP (2013) Technical aspects and inter-laboratory variability in native peptide profiling: the CE-MS experience. Clin Biochem 46:432–443CrossRefPubMed

47.

Harambat J, van Stralen KJ, Kim JJ, Tizard EJ (2012) Epidemiology of chronic kidney disease in children. Pediatr Nephrol 27:363–373CrossRefPubMedCentralPubMed

48.

Wuhl E, van Stralen KJ, Verrina E, Bjerre A, Wanner C, Heaf JG, Zurriaga O, Hoitsma A, Niaudet P, Palsson R, Ravani P, Jager KJ, Schaefer F (2013) Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract. Clin J Am Soc Nephrol 8:67–74CrossRefPubMedCentralPubMed

49.

Chevalier RL (2004) Biomarkers of congenital obstructive nephropathy: past, present and future. J Urol 172:852–857CrossRefPubMed

50.

Decramer S, Wittke S, Mischak H, Zurbig P, Walden M, Bouissou F, Bascands JL, Schanstra JP (2006) Predicting the clinical outcome of congenital unilateral ureteropelvic junction obstruction in newborn by urinary proteome analysis. Nat Med 12:398–400CrossRefPubMed

51.

Chang CP, McDill BW, Neilson JR, Joist HE, Epstein JA, Crabtree GR, Chen F (2004) Calcineurin is required in urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery. J Clin Invest 113:1051–1058CrossRefPubMedCentralPubMed

52.

Klein J, Gonzalez J, Miravete M, Caubet C, Chaaya R, Decramer S, Bandin F, Bascands JL, Buffin-Meyer B, Schanstra JP (2011) Congenital ureteropelvic junction obstruction: human disease and animal models. Int J Exp Pathol 92:168–192CrossRefPubMedCentralPubMed

53.

Decramer S, Bascands JL, Schanstra JP (2007) Non-invasive markers of ureteropelvic junction obstruction. World J Urol 25:457–465CrossRefPubMed

54.

Decramer S, Zurbig P, Wittke S, Mischak H, Bascands JL, Schanstra JP (2008) Identification of urinary biomarkers by proteomics in newborns: use in obstructive nephropathy. Contribut Nephrol 160:127–141CrossRef

55.

Drube J, Zurbig P, Schiffer E, Lau E, Ure B, Gluer S, Kirschstein M, Pape L, Decramer S, Bascands JL, Schanstra JP, Mischak H, Ehrich JH (2010) Urinary proteome analysis identifies infants but not older children requiring pyeloplasty. Pediatr Nephrol 25:1673–1678CrossRefPubMed

56.

Zurbig P, Decramer S, Dakna M, Jantos J, Good DM, Coon JJ, Bandin F, Mischak H, Bascands JL, Schanstra JP (2009) The human urinary proteome reveals high similarity between kidney aging and chronic kidney disease. Proteomics 9:2108–2117CrossRefPubMedCentralPubMed

57.

Bandin F, Siwy J, Breuil B, Mischak H, Bascands JL, Decramer S, Schanstra JP (2012) Urinary proteome analysis at 5-year followup of patients with nonoperated ureteropelvic junction obstruction suggests ongoing kidney remodeling. J Urol 187:1006–1011CrossRefPubMed

58.

Mesrobian HG (2009) The value of newborn urinary proteome analysis in the evaluation and management of ureteropelvic junction obstruction: a cost-effectiveness study. World J Urol 27:379–383CrossRefPubMed

59.

Hogan J, Dourthe ME, Blondiaux E, Jouannic JM, Garel C, Ulinski T (2012) Renal outcome in children with antenatal diagnosis of severe CAKUT. Pediatr Nephrol 27:497–502CrossRefPubMed

60.

Klein J, Lacroix C, Caubet C, Siwy J, Zurbig P, Dakna M, Muller F, Breuil B, Stalmach A, Mullen W, Mischak H, Bandin F, Monsarrat B, Bascands JL, Decramer S, Schanstra JP (2013) Fetal Urinary Peptides to Predict Postnatal Outcome of Renal Disease in Fetuses with Posterior Urethral Valves (PUV). Sci Transl Med 5:198ra106CrossRefPubMed

61.

Lopez Pereira P, Martinez Urrutia MJ, Jaureguizar E (2004) Initial and long-term management of posterior urethral valves. World J Urol 22:418–424CrossRefPubMed

62.

Nasir AA, Ameh EA, Abdur-Rahman LO, Adeniran JO, Abraham MK (2011) Posterior urethral valve. World J Pediatr 7:205–216CrossRefPubMed

63.

Morris RK, Malin GL, Quinlan-Jones E, Middleton LJ, Hemming K, Burke D, Daniels JP, Khan KS, Deeks J, Kilby MD, Percutaneous vesicoamniotic shunting in Lower Urinary Tract Obstruction Collaborative G (2013) Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial. Lancet 382:1496–1506CrossRef

64.

Siwy J, Mullen W, Golovko I, Franke J, Zurbig P (2011) Human urinary peptide database for multiple disease biomarker discovery. Proteomics Clin Appl 5:367–374CrossRefPubMed

65.

Rossing K, Mischak H, Rossing P, Schanstra JP, Wiseman A, Maahs DM (2008) The urinary proteome in diabetes and diabetes-associated complications: new ways to assess disease progression and evaluate therapy. Proteomics Clin Appl 2:997–1007CrossRefPubMed

66.

von Zur Muhlen C, Schiffer E, Zuerbig P, Kellmann M, Brasse M, Meert N, Vanholder RC, Dominiczak AF, Chen YC, Mischak H, Bode C, Peter K (2009) Evaluation of urine proteome pattern analysis for its potential to reflect coronary artery atherosclerosis in symptomatic patients. J Proteome Res 8:335–345CrossRef

67.

Zimmerli LU, Schiffer E, Zurbig P, Good DM, Kellmann M, Mouls L, Pitt AR, Coon JJ, Schmieder RE, Peter KH, Mischak H, Kolch W, Delles C, Dominiczak AF (2008) Urinary proteomic biomarkers in coronary artery disease. Mol Cell Proteomics 7:290–298CrossRefPubMed

68.

Weinstein LS, Xie T, Zhang QH, Chen M (2007) Studies of the regulation and function of the Gs alpha gene Gnas using gene targeting technology. Pharmacol Ther 115:271–291CrossRefPubMedCentralPubMed

69.

Kelsey G (2009) Epigenetics and imprinted genes: insights from the imprinted Gnas locus. Horm Res 71(Suppl 2):22–29CrossRefPubMed

70.

Mischak H, Rossing P (2010) Proteomic biomarkers in diabetic nephropathy–reality or future promise? Nephrol Dial Transplant 25:2843–2845CrossRefPubMed

71.

Schiffer E, Liabeuf S, Lacroix C, Temmar M, Renard C, Monsarrat B, Choukroun G, Lemke HD, Vanholder R, Mischak H, Massy ZA (2011) Markers of vascular disease in plasma from patients with chronic kidney disease identified by proteomic analysis. J Hypertens 29:783–790CrossRefPubMed

72.

Alkhalaf A, Zürbig 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 (2010) Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy. PloS One 5:e13421CrossRefPubMedCentralPubMed

73.

Metzger J, Kirsch T, Schiffer E, Ulger P, Mentes E, Brand K, Weissinger EM, Haubitz M, Mischak H, Herget-Rosenthal S (2010) Urinary excretion of twenty peptides forms an early and accurate diagnostic pattern of acute kidney injury. Kidney Int 78:1252–1262CrossRefPubMed

74.

Drube J, Schiffer E, Lau E, Petersen C, Kirschstein M, Kemper MJ, Lichtinghagen R, Ure B, Mischak H, Pape L, Ehrich JH (2012) Urinary proteome analysis to exclude severe vesicoureteral reflux. Pediatrics 129:e356–e363CrossRefPubMed

75.

Drube J, Schiffer E, Mischak H, Kemper MJ, Neuhaus T, Pape L, Lichtinghagen R, Ehrich JH (2009) Urinary proteome pattern in children with renal Fanconi syndrome. Nephrol Dial Transplant 24:2161–2169CrossRefPubMed

76.

Metzger J, Chatzikyrkou C, Broecker V, Schiffer E, Jaensch L, Iphoefer A, Mengel M, Mullen W, Mischak H, Haller H, Gwinner W (2011) Diagnosis of subclinical and clinical acute T-cell-mediated rejection in renal transplant patients by urinary proteome analysis. Proteomics Clin Appl 5:322–333CrossRefPubMed

Title: Proteomic urinary biomarker approach in renal disease: from discovery to implementation
Authors: Joost P. Schanstra
Harald Mischak
Publication date: 01-05-2015
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 5/2015
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-014-2790-y

At a glance: The STEP trials

Springer Medicine

Proteomic urinary biomarker approach in renal disease: from discovery to implementation

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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