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Biomarkers for renal disease in childhood

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Abstract

A kidney biopsy is currently required to diagnose lupus nephritis (LN). Invasiveness related to kidney biopsies, however, makes it a prohibitive approach in daily clinical practice for the assessment of LN-related activity and damage. The lack of accurate LN biomarkers inhibits effective testing of new, less toxic medications. Research in LN biomarkers involves two principal methods: 1) the candidate biomarker approach that tests molecules known to be involved in LN pathogenesis, and 2) broad-based biomarker-screening techniques. These methods suggest that the following may all be potent LN biomarkers: CCL2 (chemokine [C-C motif] ligand 2; also known as MCP-1 [monocyte chemotactic protein-1]); CCL5 (chemokine [C-C motif] ligand 5; also known as RANTES [regulated on activation, normal T expressed and secreted]); and CX3CL1(chemokine [C-X3-C motif] ligand 1; also known as fractalkine); IP-10 (interferoninducible protein 10; also known as chemokine [C-X-C motif] ligand 10); neutrophil gelatinase associate lipocalin; hepcidin; adiponectin; transferrin; ceruloplasmin; lipocalin-like prostaglandin synthetase-D; and orosomucoid.

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References and Recommended Reading

  1. Brunner HI, Gladman DD, Ibañez D, et al.: Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum 2008, 58:556–562.

    Article  PubMed  Google Scholar 

  2. De Gruttola VG, Clax P, DeMets DL, et al.: Considerations in the evaluation of surrogate endpoints in clinical trials. Summary of a National Institutes of Health workshop. Control Clin Trials 2001, 22:485–502.

    Article  PubMed  Google Scholar 

  3. Churg J, Sobin LH: Renal Disease: Classification and Atlas of Glomerular Diseases, edn 1. Tokyo/New York: Igaku-Shoin; 1982.

    Google Scholar 

  4. Weening JJ, D’Agati VD, Schwartz MM, et al.: The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004, 65:521–530.

    Article  PubMed  Google Scholar 

  5. Seo J, In-Gu D, Eun SP, et al.: Pathology of lupus nephritis is better classified by the International Society of Nephrology-Renal Pathology Society system. Basic Applied Pathol 2008, 1:12–17.

    Article  Google Scholar 

  6. Grootscholten C, Bajema IM, Florquin S, et al.: Interobserver agreement of scoring of histopathological characteristics and classification of lupus nephritis. Nephrol Dial Transplant 2008, 23:223–230.

    Article  PubMed  Google Scholar 

  7. Marks SD, Sebire NJ, Pilkington C, Tullus K: Clinicopathological correlations of pediatric lupus nephritis. Pediatr Nephrol 2007, 22:77–83.

    Article  PubMed  Google Scholar 

  8. Askenazi D, Myones B, Kamdar A, et al.: Outcomes of children with proliferative lupus nephritis: the role of protocol renal biopsy. Pediatr Nephrol 2007, 22:981–986.

    Article  PubMed  Google Scholar 

  9. Ho A, Barr SG, Magder LS, Petri M: A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus. Arthritis Rheum 2001, 44:2350–2357.

    Article  PubMed  CAS  Google Scholar 

  10. Ho A, Magder LS, Barr SG, Petri M: Decreases in antidouble-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus. Arthritis Rheum 2001, 44:2342–2349.

    Article  PubMed  CAS  Google Scholar 

  11. Rovin BH, Birmingham DJ, Nagaraja HN, et al.: Biomarker discovery in human SLE nephritis. Bull NYU Hosp Jt Dis 2007, 65:187–193.

    PubMed  Google Scholar 

  12. Christopher-Stine L, Siedner M, Lin J, et al.: Renal biopsy in lupus patients with low levels of proteinuria. J Rheumatol 2007, 34:332–335.

    PubMed  Google Scholar 

  13. Teramoto K, Negoro N, Kitamoto K, et al.: Microarray analysis of glomerular gene expression in murine lupus nephritis. J Pharmacol Sci 2008, 106:56–67.

    Article  PubMed  CAS  Google Scholar 

  14. Yoshimoto S, Nakatani K, Iwano M, et al.: Elevated levels of fractalkine expression and accumulation of CD16+ monocytes in glomeruli of active lupus nephritis. Am J Kidney Dis 2007, 50:47–58.

    Article  PubMed  CAS  Google Scholar 

  15. Kulkarni O, Anders HJ: Chemokines in lupus nephritis. Front Biosci 2008, 13:3312–3320.

    Article  PubMed  CAS  Google Scholar 

  16. Ferri GM, Gigante A, Ferri F, et al.: Urine chemokines: biomarkers of human lupus nephritis? Eur Rev Med Pharmacol Sci 2007, 11:171–178.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Rovin BH: The chemokine network in systemic lupus erythematous nephritis. Front Biosci 2008, 13:904–922.

    Article  PubMed  CAS  Google Scholar 

  19. Tian S, Li J, Wang L, et al.: Urinary levels of RANTES and M-CSF are predictors of lupus nephritis flare. Inflamm Res 2007, 56:304–310.

    Article  PubMed  CAS  Google Scholar 

  20. Fu Q, Chen X, Cui H, et al.: Association of elevated transcript levels of interferon-inducible chemokines with disease activity and organ damage in systemic lupus erythematosus patients. Arthritis Res Ther 2008, 10:R112.

    Article  PubMed  Google Scholar 

  21. Avihingsanon Y, Phumesin P, Benjachat T, et al.: Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis. Kidney Int 2006, 69:747–753.

    Article  PubMed  CAS  Google Scholar 

  22. Schwartz N, Michaelson JS, Putterman C: Lipocalin-2, TWEAK, and other cytokines as urinary biomarkers for lupus nephritis. Ann N Y Acad Sci 2007, 1109:265–274.

    Article  PubMed  CAS  Google Scholar 

  23. Wu T, Xie C, Wang HW, et al.: Elevated urinary VCAM-1, P-selectin, soluble TNF receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis. J Immunol 2007, 179:7166–7175.

    PubMed  CAS  Google Scholar 

  24. Pitashny M, Schwartz N, Qing X, et al.: Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis. Arthritis Rheum 2007, 56:1894–1903.

    Article  PubMed  CAS  Google Scholar 

  25. Suzuki M, Wiers KM, Klein-Gitelman MS, et al.: Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis. Pediatr Nephrol 2008, 23:403–412.

    Article  PubMed  Google Scholar 

  26. Brunner HI, Mueller M, Rutherford C, et al.: Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 2006, 54:2577–2584.

    Article  PubMed  CAS  Google Scholar 

  27. Hinze C, Suzuki M, Klein-Gitelman M, et al.: Neutrophil gelatinase-associated lipocalin (NGAL) In urine predicts the course of nephritis in pediatric systemic lupus erythematosus (pSLE). Presented at American College of Rheumatology/Association of Rheumatology Health Professionals Scientific Meeting. San Francisco, CA; October 24–29, 2008.

  28. Wu T, Mohan C: Proteomics on the diagnostic horizon: lessons from rheumatology. Am J Med Sci 2007, 333:16–25.

    Article  PubMed  Google Scholar 

  29. Portilla D, Schnackenberg L, Beger RD: Metabolomics as an extension of proteomic analysis: study of acute kidney injury. Semin Nephrol 2007, 27:609–620.

    Article  PubMed  CAS  Google Scholar 

  30. Nikpour M, Dempsey AA, Urowitz MB, et al.: Association of a gene expression profile from whole blood with disease activity in systemic lupus erythaematosus. Ann Rheum Dis 2008, 67:1069–1075.

    Article  PubMed  CAS  Google Scholar 

  31. Chaussabel D, Quinn C, Shen J, et al.: A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity 2008, 29:150–164.

    Article  PubMed  CAS  Google Scholar 

  32. Pascual V, Allantaz F, Patel P, et al.: How the study of children with rheumatic diseases identified interferon-alpha and interleukin-1 as novel therapeutic targets. Immunol Rev 2008, 223:39–59.

    Article  PubMed  CAS  Google Scholar 

  33. Arthur JM, Janech MG, Varghese SA, et al.: Diagnostic and prognostic biomarkers in acute renal failure. Contrib Nephrol 2008, 160:53–64.

    Article  PubMed  CAS  Google Scholar 

  34. Suzuki M, Ross GF, Wiers K, et al.: Identification of a urinary proteomic signature for lupus nephritis in children. Pediatr Nephrol 2007, 22:2047–2057.

    Article  PubMed  Google Scholar 

  35. Wu T, Mohan C: Three pathogenic determinants in immune nephritis—anti-glomerular antibody specificity, innate triggers and host genetics. Front Biosci 2007, 12:2207–2211.

    Article  PubMed  CAS  Google Scholar 

  36. Wu T, Xie C, Bhaskarabhatla M, et al.: Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance. Arthritis Rheum 2007, 56:949–959.

    Article  PubMed  CAS  Google Scholar 

  37. Zhang X, Jin M, Wu H, et al.: Biomarkers of lupus nephritis determined by serial urine proteomics. Kidney Int 2008, 74:799–807.

    Article  PubMed  CAS  Google Scholar 

  38. Suzuki M, Wiers K, Brooks E, et al.: Initial validation of a novel protein biomarker panel for active lupus nephritis. Ped Res 2009 (in press).

  39. Varghese SA, Powell TB, Budisavljevic MN, et al.: Urine biomarkers predict the cause of glomerular disease. J Am Soc Nephrol 2007, 18:913–922.

    Article  PubMed  CAS  Google Scholar 

  40. Fessatou S, Nicolaidou P, Gourgiotis D, et al.: Endothelin 1 levels in relation to clinical presentation and outcome of Henoch Schonlein purpura. BMC Pediatr 2008, 8:33.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA

    Hermine I. Brunner

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  1. Lena Das
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  2. Hermine I. Brunner
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Correspondence to Hermine I. Brunner.

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Das, L., Brunner, H.I. Biomarkers for renal disease in childhood. Curr Rheumatol Rep 11, 218–225 (2009). https://doi.org/10.1007/s11926-009-0030-4

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