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Urine biomarkers in juvenile-onset SLE nephritis

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Abstract

Over 80 % of patients with juvenile-onset systemic lupus erythematosus will have renal involvement compared to 40 % with adult-onset disease. Up to 44 % of children who do have lupus nephritis (LN) progress to renal failure in early adulthood. Improved methods of detecting onset of LN would allow earlier treatment, which may prevent irreversible renal scarring and a decline in renal function. Current conventional markers of disease activity fail to adequately predict renal lupus flares and include proteinuria, complement levels, anti-double-stranded DNA antibodies and serum creatinine concentrations. Standardized histological classification is currently the gold standard for diagnosing and classifying LN, but its invasive nature limits routine use for monitoring, especially in a childhood population. Novel biomarkers need to be sensitive and specific—and preferably non-invasive and cost-effective. The most promising biomarkers in juvenile-onset LN include urinary neutrophil gelatinase associated lipocalin, monocyte chemoattractant protein 1 and transforming growth factor-beta, although many others have been identified and are under investigation. No one biomarker yet discovered is unique to LN, indicating an overlap in disease pathophysiology. It is likely that a combination of biomarkers will be required for assessing disease flare detection, response to treatment and prognostic information. Potential biomarkers require longitudinal validation in large paediatric, prospective cohorts to assess their ability to act as clinically useful adjuncts.

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References

  1. Midgley A, Beresford MW (2011) Cellular localization of nuclear antigen during neutrophil apoptosis: mechanism for autoantigen exposure? Lupus 20:641–646

    Article  PubMed  CAS  Google Scholar 

  2. Tucker LB, Menon S, Schaller JG, Isenberg DA (1995) Adult- and childhood-onset systemic lupus erythematosus: a comparison of onset, clinical features, serology, and outcome. Br J Rheumatol 34:866–872

    Article  PubMed  CAS  Google Scholar 

  3. Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR (2002) Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 360:1197–1202

    Article  PubMed  Google Scholar 

  4. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Article  PubMed  CAS  Google Scholar 

  5. Hersh AO, Trupin L, Yazdany J, Panopalis P, Julian L, Katz P, Criswell LA, Yelin E (2010) Childhood-onset disease as a predictor of mortality in an adult cohort of patients with systemic lupus erythematosus. Arthritis Care Res (Hoboken) 62:1152–1159

    Article  Google Scholar 

  6. Hagelberg S, Lee Y, Bargman J, Mah G, Schneider R, Laskin C, Eddy A, Gladman D, Urowitz M, Hebert D, Silverman E (2002) Longterm followup of childhood lupus nephritis. J Rheumatol 29:2635–2642

    PubMed  Google Scholar 

  7. Levy M, Montes de Oca M, Claude-Babron M (1994) Unfavorable outcomes (end-stage renal failure/death) in childhood onset systemic lupus erythematosus A multicenter study in Paris and its environs. Clin Exp Rheumatol 12(Suppl 10):S63–S68

    Article  PubMed  Google Scholar 

  8. Watson L, Leone V, Pilkington C, Tullus K, Rangaraj S, McDonagh JE, Gardner-Medwin J, Wilkinson N, Riley P, Tizard J, Armon K, Sinha MD, Ioannou Y, Archer N, Bailey K, Davidson J, Baildam EM, Cleary G, McCann LJ, Beresford MW (2012) Juvenile-onset SLE; disease activity, severity and damage—the UK JSLE Cohort Study. Arthritis Rheum. doi:10.1002/art.34410

  9. Marini R, Costallat LT (1999) Young age at onset, renal involvement, and arterial hypertension are of adverse prognostic significance in juvenile systemic lupus erythematosus. Rev Rhum Engl Ed 66:303–309

    PubMed  CAS  Google Scholar 

  10. Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 15:241–250

    Article  PubMed  Google Scholar 

  11. Hiramatsu N, Kuroiwa T, Ikeuchi H, Maeshima A, Kaneko Y, Hiromura K, Ueki K, Nojima Y (2008) Revised classification of lupus nephritis is valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions. Rheumatology (Oxford) 47:702–707

    Article  CAS  Google Scholar 

  12. Marks SD, Tullus K, Sebire NJ (2006) Current issues in pediatric lupus nephritis: role of revised histopathological classification. Fetal Pediatr Pathol 25:297–309

    Article  PubMed  Google Scholar 

  13. Esdaile JM (1998) Current role of renal biopsy in patients with SLE. Baillieres Clin Rheumatol 12:433–448

    Article  PubMed  CAS  Google Scholar 

  14. Askenazi D, Myones B, Kamdar A, Warren R, Perez M, De Guzman M, Minta A, Hicks MJ, Kale A (2007) Outcomes of children with proliferative lupus nephritis: the role of protocol renal biopsy. Pediatr Nephrol 22:981–986

    Article  PubMed  Google Scholar 

  15. Hiraki LT, Lu B, Alexander SR, Shaykevich T, Alarcon GS, Solomon DH, Winkelmayer WC, Costenbader KH (2011) End-stage renal disease due to lupus nephritis among children in the US, 1995–2006. Arthritis Rheum 63:1988–1997

    Article  PubMed  Google Scholar 

  16. Ravelli A, Duarte-Salazar C, Buratti S, Reiff A, Bernstein B, Maldonado-Velazquez MR, Beristain-Manterola R, Maeno N, Takei S, Gerloni V, Spencer CH, Pratsidou-Gertsi P, Ruperto N, Pistorio A, Martini A (2003) Assessment of damage in juvenile-onset systemic lupus erythematosus: a multicenter cohort study. Arthritis Rheum 49:501–507

    Article  PubMed  Google Scholar 

  17. Brunner HI, Gladman DD, Ibanez D, Urowitz MD, Silverman ED (2008) Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum 58:556–562

    Article  PubMed  Google Scholar 

  18. Mina R, von Scheven E, Ardoin SP, Eberhard BA, Punaro M, Ilowite N, Hsu J, Klein-Gitelman M, Moorthy LN, Muscal E, Radhakrishna SM, Wagner-Weiner L, Adams M, Blier P, Buckley L, Chalom E, Chedeville G, Eichenfield A, Fish N, Henrickson M, Hersh AO, Hollister R, Jones O, Jung L, Levy D, Lopez-Benitez J, McCurdy D, Miettunen PM, Quintero-Del Rio AI, Rothman D, Rullo O, Ruth N, Schanberg LE, Silverman E, Singer NG, Soep J, Syed R, Vogler LB, Yalcindag A, Yildirim-Toruner C, Wallace CA, Brunner HI (2012) Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus. Arthritis Care Res (Hoboken) 64:375–383

    Article  Google Scholar 

  19. Kazyra I, Pilkington C, Marks SD, Tullus K (2010) Mycophenolate mofetil treatment in children and adolescents with lupus. Arch Dis Child 95:1059–1061

    Article  PubMed  Google Scholar 

  20. Pons-Estel GJ, Alarcon GS, McGwin G Jr, Danila MI, Zhang J, Bastian HM, Reveille JD, Vila LM (2009) Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum 61:830–839

    Article  PubMed  CAS  Google Scholar 

  21. Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G (2012) Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: The lupus nephritis assessment with rituximab (LUNAR) study. Arthritis Rheum 64:1215–1226.

    Google Scholar 

  22. Pepper R, Griffith M, Kirwan C, Levy J, Taube D, Pusey C, Lightstone L, Cairns T (2009) Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids. Nephrol Dial Transplant 24:3717–3723

    Article  PubMed  CAS  Google Scholar 

  23. Podolskaya A, Stadermann M, Pilkington C, Marks SD, Tullus K (2008) B cell depletion therapy for 19 patients with refractory systemic lupus erythematosus. Arch Dis Child 93:401–406

    Article  PubMed  CAS  Google Scholar 

  24. Mak A, Mok CC, Chu WP, To CH, Wong SN, Au TC (2007) Renal damage in systemic lupus erythematosus: a comparative analysis of different age groups. Lupus 16:28–34

    Article  PubMed  CAS  Google Scholar 

  25. Norby GE, Strom EH, Midtvedt K, Hartmann A, Gilboe IM, Leivestad T, Stenstrom J, Holdaas H (2010) Recurrent lupus nephritis after kidney transplantation: a surveillance biopsy study. Ann Rheum Dis 69:1484–1487

    Article  PubMed  Google Scholar 

  26. Isenberg DA, Rahman A, Allen E, Farewell V, Akil M, Bruce IN, D'Cruz D, Griffiths B, Khamashta M, Maddison P, McHugh N, Snaith M, The LS, Yee CS, Zoma A, Gordon C (2005) BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus. Rheumatology (Oxford) 44:902–906

    Article  CAS  Google Scholar 

  27. Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291

    PubMed  Google Scholar 

  28. Siedner MJ, Gelber AC, Rovin BH, McKinley AM, Christopher-Stine L, Astor B, Petri M, Fine DM (2008) Diagnostic accuracy study of urine dipstick in relation to 24-hour measurement as a screening tool for proteinuria in lupus nephritis. J Rheumatol 35:84–90

    PubMed  Google Scholar 

  29. Cottiero RA, Madaio MP, Levey AS (1995) Glomerular filtration rate and urinary albumin excretion rate in systemic lupus erythematosus. Nephron 69:140–146

    Article  PubMed  CAS  Google Scholar 

  30. Leung YY, Szeto CC, Tam LS, Lam CW, Li EK, Wong KC, Yu SW, Kun EW (2007) Urine protein-to-creatinine ratio in an untimed urine collection is a reliable measure of proteinuria in lupus nephritis. Rheumatology (Oxford) 46:649–652

    Article  CAS  Google Scholar 

  31. Christopher-Stine L, Siedner M, Lin J, Haas M, Parekh H, Petri M, Fine DM (2007) Renal biopsy in lupus patients with low levels of proteinuria. J Rheumatol 34:332–335

    PubMed  Google Scholar 

  32. Fine DM, Ziegenbein M, Petri M, Han EC, McKinley AM, Chellini JW, Nagaraja HN, Carson KA, Rovin BH (2009) A prospective study of protein excretion using short-interval timed urine collections in patients with lupus nephritis. Kidney Int 76:1284–1288

    Article  PubMed  CAS  Google Scholar 

  33. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    PubMed  CAS  Google Scholar 

  34. Ayodele OE, Okpechi IG, Swanepoel CR (2010) Predictors of poor renal outcome in patients with biopsy-proven lupus nephritis. Nephrology (Carlton) 15:482–490

    Article  Google Scholar 

  35. Woolf A, Croker B, Osofsky SG, Kredich DW (1979) Nephritis in children and young adults with systemic lupus erythematosus and normal urinary sediment. Pediatrics 64:678–685

    PubMed  CAS  Google Scholar 

  36. Nasiri S, Karimifar M, Bonakdar ZS, Salesi M (2010) Correlation of ESR, C3, C4, anti-DNA and lupus activity based on British Isles Lupus Assessment Group Index in patients of rheumatology clinic. Rheumatol Int 30:1605–1609

    Article  PubMed  CAS  Google Scholar 

  37. Kasitanon N, Magder LS, Petri M (2006) Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore) 85:147–156

    Article  Google Scholar 

  38. Moroni G, Radice A, Giammarresi G, Quaglini S, Gallelli B, Leoni A, Li Vecchi M, Messa P, Sinico RA (2009) Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis. Ann Rheum Dis 68:234–237

    Article  PubMed  CAS  Google Scholar 

  39. Welch TR, Blystone LW (2009) Renal disease associated with inherited disorders of the complement system. Pediatr Nephrol 24:1439–1444

    Article  PubMed  Google Scholar 

  40. Al-Mayouf SM, Abanomi H, Eldali A (2011) Impact of C1q deficiency on the severity and outcome of childhood systemic lupus erythematosus. Int J Rheum Dis 14:81–85

    Article  PubMed  Google Scholar 

  41. Jesus AA, Silva CA, Carneiro-Sampaio M, Sheinberg M, Mangueira CL, Marie SK, Liphaus BL (2009) Anti-C1q antibodies in juvenile-onset systemic lupus erythematosus. Ann N Y Acad Sci 1173:235–238

    Article  PubMed  CAS  Google Scholar 

  42. Akhter E, Burlingame RW, Seaman AL, Magder L, Petri M (2011) Anti-C1q antibodies have higher correlation with flares of lupus nephritis than other serum markers. Lupus 20:1267–1274

    Article  PubMed  CAS  Google Scholar 

  43. Matrat A, Veysseyre-Balter C, Trolliet P, Villar E, Dijoud F, Bienvenu J, Fabien N (2011) Simultaneous detection of anti-C1q and anti-double stranded DNA autoantibodies in lupus nephritis: predictive value for renal flares. Lupus 20:28–34

    Article  PubMed  CAS  Google Scholar 

  44. Katsumata Y, Miyake K, Kawaguchi Y, Okamoto Y, Kawamoto M, Gono T, Baba S, Hara M, Yamanaka H (2011) Anti-C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis: a controlled study of 126 consecutive patients. Arthritis Rheum 63:2436–2444

    Article  PubMed  CAS  Google Scholar 

  45. Eriksson C, Kokkonen H, Johansson M, Hallmans G, Wadell G, Rantapaa-Dahlqvist S (2011) Autoantibodies predate the onset of systemic lupus erythematosus in northern Sweden. Arthritis Res Ther 13:30

    Article  Google Scholar 

  46. Campos LM, Kiss MH, Scheinberg MA, Mangueira CL, Silva CA (2006) Antinucleosome antibodies in patients with juvenile systemic lupus erythematosus. Lupus 15:496–500

    Article  PubMed  CAS  Google Scholar 

  47. Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95

    Article  Google Scholar 

  48. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640

    Article  PubMed  CAS  Google Scholar 

  49. Marks SD, Shah V, Pilkington C, Tullus K (2010) Urinary monocyte chemoattractant protein-1 correlates with disease activity in lupus nephritis. Pediatr Nephrol 25:2283–2288

    Article  PubMed  Google Scholar 

  50. Rovin BH, Song H, Birmingham DJ, Hebert LA, Yu CY, Nagaraja HN (2005) Urine chemokines as biomarkers of human systemic lupus erythematosus activity. J Am Soc Nephrol 16:467–473

    Article  PubMed  CAS  Google Scholar 

  51. Gwira JA, Wei F, Ishibe S, Ueland JM, Barasch J, Cantley LG (2005) Expression of neutrophil gelatinase-associated lipocalin regulates epithelial morphogenesis in vitro. J Biol Chem 280:7875–7882

    Article  PubMed  CAS  Google Scholar 

  52. Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J, Jain A, Bullington N, Devarajan P (2006) Urinary neutrophil gelatinase-associated lipocalcin in D + HUS: a novel marker of renal injury. Pediatr Nephrol 21:989–994

    Article  PubMed  Google Scholar 

  53. Hollmen ME, Kyllonen LE, Inkinen KA, Lalla ML, Salmela KT (2011) Urine neutrophil gelatinase-associated lipocalin is a marker of graft recovery after kidney transplantation. Kidney Int 79:89–98

    Article  PubMed  CAS  Google Scholar 

  54. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A (2009) Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 54:1012–1024

    Article  PubMed  CAS  Google Scholar 

  55. Viau A, El Karoui K, Laouari D, Burtin M, Nguyen C, Mori K, Pillebout E, Berger T, Mak TW, Knebelmann B, Friedlander G, Barasch J, Terzi F (2010) Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J Clin Invest 120:4065–4076

    Article  PubMed  CAS  Google Scholar 

  56. Pawar RD, Pitashny M, Gindea S, Tan Tieng A, Levine B, Goilav B, Campbell SR, Xia Y, Qing X, Thomas D, Herlitz L, Berger T, Mak TM, Putterman C (2012) Neutrophil gelatinase associated lipocalin is instrumental in the pathogenesis of antibody-mediated nephritis. Arthritis Rheum. 64:1620–1631.

    Google Scholar 

  57. Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, Mishra J, Devarajan P (2006) Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 54:2577–2584

    Article  PubMed  CAS  Google Scholar 

  58. Rubinstein T, Pitashny M, Levine B, Schwartz N, Schwartzman J, Weinstein E, Pego-Reigosa JM, Lu TY, Isenberg D, Rahman A, Putterman C (2010) Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis. Rheumatology (Oxford) 49:960–971

    Article  CAS  Google Scholar 

  59. Suzuki M, Wiers KM, Klein-Gitelman MS, Haines KA, Olson J, Onel KB, O'Neil K, Passo MH, Singer NG, Tucker L, Ying J, Devarajan P, Brunner HI (2008) Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis. Pediatr Nephrol 23:403–412

    Article  PubMed  Google Scholar 

  60. Hinze CH, Suzuki M, Klein-Gitelman M, Passo MH, Olson J, Singer NG, Haines KA, Onel K, O'Neil K, Silverman ED, Tucker L, Ying J, Devarajan P, Brunner HI (2009) Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis Rheum 60:2772–2781

    Article  PubMed  Google Scholar 

  61. Yilmaz A, Sevketoglu E, Gedikbasi A, Karyagar S, Kiyak A, Mulazimoglu M, Aydogan G, Ozpacaci T, Hatipoglu S (2009) Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatr Nephrol 24:2387–2392

    Article  PubMed  Google Scholar 

  62. Matoba K, Kawanami D, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K (2010) Rho-kinase mediates TNF-alpha-induced MCP-1 expression via p38 MAPK signaling pathway in mesangial cells. Biochem Biophys Res Commun 402:725–730

    Article  PubMed  CAS  Google Scholar 

  63. Tarabra E, Giunti S, Barutta F, Salvidio G, Burt D, Deferrari G, Gambino R, Vergola D, Pinach S, Perin PC, Camussi G, Gruden G (2009) Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system on nephrin expression in streptozotocin-treated mice and human cultured podocytes. Diabetes 58:2109–2118

    Article  PubMed  CAS  Google Scholar 

  64. Marks SD, Williams SJ, Tullus K, Sebire NJ (2008) Glomerular expression of monocyte chemoattractant protein-1 is predictive of poor renal prognosis in pediatric lupus nephritis. Nephrol Dial Transpl 23:3521–3526

    Article  CAS  Google Scholar 

  65. Wada T, Yokoyama H, Su SB, Mukaida N, Iwano M, Dohi K, Takahashi Y, Sasaki T, Furuichi K, Segawa C, Hisada Y, Ohta S, Takasawa K, Kobayashi K, Matsushima K (1996) Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis. Kidney Int 49:761–767

    Article  PubMed  CAS  Google Scholar 

  66. El-Shehaby A, Darweesh H, El-Khatib M, Momtaz M, Marzouk S, El-Shaarawy N, Emad Y (2011) Correlations of urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and IL-8 with lupus nephritis. J Clin Immunol 31:848–856

    Article  PubMed  CAS  Google Scholar 

  67. Watson L, Midgley A, Pilkington C, Tullus K, Marks SD, Holt RC, Jones CA, Beresford MW (2011) Urinary monocyte chemoattractant protein 1 and alpha 1 acid glycoprotein as biomarkers of renal disease activity in juvenile-onset systemic lupus erythematosus. Lupus 21:496–501

    Article  PubMed  Google Scholar 

  68. Szeto CC, Chan RW, Lai KB, Szeto CY, Chow KM, Li PK, Lai FM (2005) Messenger RNA expression of target genes in the urinary sediment of patients with chronic kidney diseases. Nephrol Dial Transplant 20:105–113

    Article  PubMed  CAS  Google Scholar 

  69. Avihingsanon Y, Phumesin P, Benjachat T, Akkasilpa S, Kittikowit V, Praditpornsilpa K, Wongpiyabavorn J, Eiam-Ong S, Hemachudha T, Tungsanga K, Hirankarn N (2006) Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis. Kidney Int 69:747–753

    Article  PubMed  CAS  Google Scholar 

  70. Hammad AM, Youssef HM, El-Arman MM (2006) Transforming growth factor beta 1 in children with systemic lupus erythematosus: a possible relation with clinical presentation of lupus nephritis. Lupus 15:608–612

    Article  PubMed  CAS  Google Scholar 

  71. Marks SD, Shah V, Pilkington C, Woo P, Dillon MJ (2005) Renal tubular dysfunction in children with systemic lupus erythematosus. Pediatr Nephrol 20:141–148

    Article  PubMed  Google Scholar 

  72. Erdener D, Aksu K, Bicer I, Doganavsargil E, Kutay FZ (2005) Urinary N-acetyl-beta-D-glucosaminidase (NAG) in lupus nephritis and rheumatoid arthritis. J Clin Lab Anal 19:172–176

    Article  PubMed  CAS  Google Scholar 

  73. Sesso R, Rettori R, Nishida S, Sato E, Ajzen H, Pereira AB (1994) Assessment of lupus nephritis activity using urinary retinol-binding protein. Nephrol Dial Transplant 9:367–371

    PubMed  CAS  Google Scholar 

  74. Skalova S, Rejtar P, Kutilek S (2009) Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activity in children with vesicoureteral reflux. Bratisl Lek Listy 110:69–72

    PubMed  CAS  Google Scholar 

  75. Florkowski CM, Jones AF, Guy JM, Husband DJ, Stevens J (1994) Retinol binding proteinuria and phosphaturia: markers of paracetamol-induced nephrotoxicity. Ann Clin Biochem 31:331–334

    PubMed  Google Scholar 

  76. Suzuki M, Wiers K, Brooks EB, Greis KD, Haines K, Klein-Gitelman MS, Olson J, Onel K, O'Neil KM, Silverman ED, Tucker L, Ying J, Devarajan P, Brunner HI (2009) Initial validation of a novel protein biomarker panel for active pediatric lupus nephritis. Pediatr Res 65:530–536

    Article  PubMed  CAS  Google Scholar 

  77. Bauer JW, Petri M, Batliwalla FM, Koeuth T, Wilson J, Slattery C, Panoskaltsis-Mortari A, Gregersen PK, Behrens TW, Baechler EC (2009) Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: a validation study. Arthritis Rheum 60:3098–3107

    Article  PubMed  CAS  Google Scholar 

  78. Lu J, Kwan BC, Lai FM, Choi PC, Tam LS, Li EK, Chow KM, Wang G, Li PK, Szeto CC (2011) Gene expression of TWEAK/Fn14 and IP-10/CXCR3 in glomerulus and tubulointerstitium of patients with lupus nephritis. Nephrology (Carlton) 16:426–432

    Article  CAS  Google Scholar 

  79. Sanz AB, Sanchez-Nino MD, Ortiz A (2011) TWEAK, a multifunctional cytokine in kidney injury. Kidney Int 80:708–718

    Article  PubMed  CAS  Google Scholar 

  80. Schwartz N, Rubinstein T, Burkly LC, Collins CE, Blanco I, Su L, Hojaili B, Mackay M, Aranow C, Stohl W, Rovin BH, Michaelson JS, Putterman C (2009) Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study. Arthritis Res Ther 11:143

    Article  Google Scholar 

  81. Yokoyama H, Takaeda M, Wada T, Ohta S, Hisada Y, Segawa C, Furuichi K, Kobayashi K (1997) Glomerular ICAM-1 expression related to circulating TNF-alpha in human glomerulonephritis. Nephron 76:425–433

    Article  PubMed  CAS  Google Scholar 

  82. Abd-Elkareem MI, Al Tamimy HM, Khamis OA, Abdellatif SS, Hussein MR (2010) Increased urinary levels of the leukocyte adhesion molecules ICAM-1 and VCAM-1 in human lupus nephritis with advanced renal histological changes: preliminary findings. Clin Exp Nephrol 14:548–557

    Article  PubMed  CAS  Google Scholar 

  83. Molad Y, Miroshnik E, Sulkes J, Pitlik S, Weinberger A, Monselise Y (2002) Urinary soluble VCAM-1 in systemic lupus erythematosus: a clinical marker for monitoring disease activity and damage. Clin Exp Rheumatol 20:403–406

    PubMed  CAS  Google Scholar 

  84. 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 74:799–807

    Article  PubMed  CAS  Google Scholar 

  85. 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 18:913–922

    Article  PubMed  CAS  Google Scholar 

  86. 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. Pediatr Nephrol 22:2047–2057

    Article  PubMed  Google Scholar 

  87. Fu Q, Chen X, Cui H, Guo Y, Chen J, Shen N, Bao C (2008) Association of elevated transcript levels of interferon-inducible chemokines with disease activity and organ damage in systemic lupus erythematosus patients. Arthritis Res Ther 10:112

    Article  Google Scholar 

  88. Chan RW, Tam LS, Li EK, Lai FM, Chow KM, Lai KB, Li PK, Szeto CC (2003) Inflammatory cytokine gene expression in the urinary sediment of patients with lupus nephritis. Arthritis Rheum 48:1326–1331

    Article  PubMed  CAS  Google Scholar 

  89. Chan RW, Lai FM, Li EK, Tam LS, Chow KM, Lai KB, Li PK, Szeto CC (2007) Intrarenal cytokine gene expression in lupus nephritis. Ann Rheum Dis 66:886–892

    Article  PubMed  CAS  Google Scholar 

  90. Avihingsanon Y, Benjachat T, Tassanarong A, Sodsai P, Kittikovit V, Hirankarn N (2009) Decreased renal expression of vascular endothelial growth factor in lupus nephritis is associated with worse prognosis. Kidney Int 75:1340–1348

    Article  PubMed  CAS  Google Scholar 

  91. Edelbauer M, Kshirsagar S, Riedl M, Billing H, Tonshoff B, Haffner D, Dotsch J, Wechselberger G, Weber LT, Steichen-Gersdorf E (2012) Soluble VEGF receptor 1 promotes endothelial injury in children and adolescents with lupus nephritis. Pediatr Nephrol 27:793–800.

    Google Scholar 

  92. Dhaun N, Lilitkarntakul P, Macintyre IM, Muilwijk E, Johnston NR, Kluth DC, Webb DJ, Goddard J (2009) Urinary endothelin-1 in chronic kidney disease and as a marker of disease activity in lupus nephritis. Am J Physiol Renal Physiol 296:1477–1483

    Article  Google Scholar 

  93. Wang G, Lai FM, Tam LS, Li EK, Kwan BC, Chow KM, Li PK, Szeto CC (2009) Urinary FOXP3 mRNA in patients with lupus nephritis–relation with disease activity and treatment response. Rheumatology (Oxford) 48:755–760

    Article  CAS  Google Scholar 

  94. Brunner HI, Bennett MR, Mina R, Suzuki M, Petri M, Kiani AN, Pendl J, Witte D, Ying J, Rovin BH, Devarajan P (2012) Non-invasive renal protein biomarkers are associated with histological features of lupus nephritis. Arthritis Rheum. doi:10.1002/art.34426

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Correspondence to Louise Watson.

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Watson, L., Beresford, M.W. Urine biomarkers in juvenile-onset SLE nephritis. Pediatr Nephrol 28, 363–374 (2013). https://doi.org/10.1007/s00467-012-2184-y

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  • DOI: https://doi.org/10.1007/s00467-012-2184-y

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