Proteinuria Severity in Lupus Nephritis is Associated with Anti-dsDNA Level and Immune Complex Deposit Location in Kidney

Authors

  • Katherina Engli Department of Clinical Pathology Faculty of Medicine, University of Brawijaya, Veteran street, Malang 65145, East Java, Indonesia; Saiful Anwar Public Hospital, 2nd Jaksa Agung Suprapto street, Malang 65112, East Java, Indonesia.
  • Kusworini Handono Department of Clinical Pathology Faculty of Medicine, University of Brawijaya, Veteran street, Malang 65145, East Java, Indonesia; Saiful Anwar Public Hospital, 2nd Jaksa Agung Suprapto street, Malang 65112, East Java, Indonesia.
  • Mudjiwijono Handaru Eko Department of Anatomical Pathology Faculty of Medicine, University of Brawijaya, Veteran street, Malang 65145, East Java, Indonesia; Saiful Anwar Public Hospital, 2nd Jaksa Agung Suprapto street, Malang 65112, East Java, Indonesia.
  • Hani Susianti Department of Clinical Pathology Faculty of Medicine, University of Brawijaya, Veteran street, Malang 65145, East Java, Indonesia; Saiful Anwar Public Hospital, 2nd Jaksa Agung Suprapto street, Malang 65112, East Java, Indonesia.
  • Atma Gunawan Internal Medicine Department Faculty of Medicine, University of Brawijaya, Veteran street, Malang 65145, East Java, Indonesia; Saiful Anwar Public Hospital, 2nd Jaksa Agung Suprapto street, Malang 65112, East Java, Indonesia.
  • Handono Kalim Internal Medicine Department Faculty of Medicine, University of Brawijaya, Veteran street, Malang 65145, East Java, Indonesia; Saiful Anwar Public Hospital, 2nd Jaksa Agung Suprapto street, Malang 65112, East Java, Indonesia.

DOI:

https://doi.org/10.11594/jtls.08.03.03

Keywords:

anti-dsDNA, immune complex, lupus nephritis, proteinuria

Abstract

Lupus nephritis (LN) is one of the manifestations of Systemic Lupus Erythematosus (SLE), with proteinuria being one of the clinical manifestations. The proteinuria pathogenesis is associated with anti-dsDNA antibody and the location of immune complex deposits within the kidney. This study aims to investigate the correlation of the severity of proteinuria with the location of immune complex deposits and the level of anti-dsDNA antibody in LN. Data were collected in cross-section. Fifty-three patients with LN in Saiful Anwar Hospital Malang, who underwent renal biopsy, were included. Hematoxylin-eosin staining and immunofluorescence analysis were used to assign subjects to different histopathological classes and determine the immune complex deposits. The spot urine samples were evaluated using the dipstick method for semi-quantitative proteinuria. The anti-dsDNA antibody levels were evaluated using the enzyme-linked immunosorbent assay (ELISA). Turbidity and enzymatic tests were conducted to elucidate urine protein and creatinine content, respectively. The level of proteinuria is significantly different among the different locations of immune complex based on the dipstick and protein/creatinine methods (p = 0.021 and p = 0.005, respectively). There was a significant correlation between anti-dsDNA antibody level and the severity of proteinuria (r = 0.326 based on dipstick and r = 0.28 based on protein/creatinine method). Thus, proteinuria in LN is determined by anti-dsDNA level and the location of immune complex deposits in the kidney.

References

Isbagio H, Kasjmir Y, Setyohadi B, Suarjana N (2009) Lupus eritematosus sistemik. In: Sudoyo A, Setiyohadi B, Alwi I et al., eds. Buku ajar ilmu penyakit dalam. Jakarta, Interna Publishing. pp 2565 - 2579.

Bagavant H, Fu SM (2009) Pathogenesis of kidney disease in systemic lupus erythematosus. Current Opinion in Rheumatology 21 (5): 489 – 494. doi: 10.1097/BOR.0b013e32832efff1.

Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. The New England Journal of Medicine 358 (9): 929 – 939. doi: 10.1056/NEJMra071297.

Danchenko N, Satia JA, Anthony MS (2006) Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 15 (5): 308 – 318. doi: 10.1191/0961203306lu2305xx.

Kasjmir YI, Handono K, Wijaya LK et al. (2011) Rekomendasi perhimpunan reumatologi Indonesia untuk diagnosis dan pengelolaan lupus eritematosus sistemik. Jakarta, Perhimpunan Reumatologi Indonesia.

Contreras G, Pardo V, Cely C et al. (2005) Factors associated with poor outcomes in patients with lupus nephritis. Lupus 14 (11): 890 – 895. doi: 10.1191/0961203305lu2238oa.

Beck L, Bomback AS, Choi MJ et al. (2013) KDOQI US commentary on the 2012 KDIGO Clinical practice guideline for glomerulonephritis. American Journal of Kidney Diseases 62 (3): 403 – 441. doi: 10.1053/j.ajkd.2013.06.002.

Handono K (2010) Peran polimorfisme gen interferon-g (IFNG) pada fenotip histologi nefritis lupus. Indonesian Journal of Clinical Pathology and Medical Laboratory 17 (1): 38 – 43.

Bawazier L, Dharmeizar, Markum H (2009) Nefritis lupus. In: Sudoyo A, Setiyohadi B, Alwi I, et al., eds. Buku ajar ilmu penyakit dalam. Jakarta, Interna Publishing. pp 983 – 991.

Stankeviciute N, Jao W, Bakir A, Lash JP (1997) Mesangial lu-

pus nephritis with the associated nephrotic syndrome. Journal of the American Society of Nephrology 8 (7): 1199 – 1204.

Weening JJ, D'Agati VD, Schwartz MM et al. (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Journal of the American Society Nephrology 15 (2): 241 – 250. doi: 10.1097/01.asn.0000108969.21691.5d.

Han TS, Schwartz MM, Lewis EJ (2006) Association of glomerular podocytopathy and nephrotic proteinuria in mesangial lupus nephritis. Lupus 15 (2): 71 – 75. doi: 10.1191/09612033

lu2264oa.

Cozzani E, Drosera M, Gasparini G, Parodi A (2014) Serology of lupus erythematosus: Correlation between immunopathological features and clinical aspects. Autoimmune Diseases 2014: 1 – 13. doi: 10.1155/2014/321359.

Waldman M, Madaio M (2005) Pathogenic autoantibodies in lupus nephritis. Lupus 14 (1): 19 – 24. doi: 10.1191/09612033

lu2054oa.

Villalta D, Bizzaro N, Bassi N et al. (2013) Anti-dsDNA antibody isotypes in systemic lupus erythematosus: IgA in Addition to IgG Anti-dsDNA help to identify glomerulonephritis and active disease. PLoS ONE 8 (8): e71458. doi: 10.1371/journal.pone.0071458.

D'Agati VD, Appel GB (2007) Lupus nephritis: Pathology and pathogenesis. In: Wallace DJ, Hahn BH, eds. Duboi’s lupus erythematosus. 7th ed. Philadelphia, Lippincott William and Wilkins. pp 1094 – 1111.

Yung S, Chan TM (2008) Anti-DNA antibodies in the pathogenesis of lupus nephritis-the emerging mechanisms. Autoimmunity Reviews 7 (4): 317 – 321. doi: 10.1016/j.autrev.2007.12.

Moroni G, Quaglini S, Radice A et al. (2015) The value of a panel of autoantibodies for predicting the activity of lupus nephritis at time of renal biopsy. Journal of Immunology Research 2015: 1 – 8. doi: 10.1155/2015/106904.

Xuejing Z, Jiazhen T, Jun L et al. (2012) Urinary TWEAK level as a marker of lupus nephritis activity in 46 cases. Journal of Biomedicine and Biotechnology 2012: 1 – 7. doi: 10.1155/2012/

KDIGO (2013) KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International Supplements 3 (1).

Price CP, Newall RG, Boyd JC (2005) Use of protein: Creatinine ratio measurements on random urine samples for prediction of significant proteinuria: A systematic review. Clinical Chemistry 51 (9): 1577 – 1586. doi: 10.1373/clinchem.2005.049742.

Dahlan S (2010) Besar sampel dan cara pengambilan sampel dalam penelitian kedokteran dan kesehatan. Jakarta, Penerbit Salemba Medika.

Bancroft JD, Gamble M (2008) Theory and practice of histological techniques. Amsterdam, Elsevier Health Sciences. pp 105 – 121.

Dooley M, Aranow C, Ginzler E (2004) Review of ACR renal criteria in systemic lupus erythematosus. Lupus.; 13(11):857-60. doi: 10.1191/0961203304lu2023oa.

Bevra HH, Maureen M, Alan W et al. (2012) American College of Rheumatology guidelines for screening, case definition, treatment and management of lupus nephritis. Arthritis Care and Research 64 (6): 797 – 808. doi: 10.1002/acr.21664.

Miller FW, Cooper GS (2007) The environmental aspect of lupus. In: Wallace DJ, Hahn BH Eds. Duboi’s lupus erythematosus. 7th ed. Philadelphia, Lippincott William and Wilkins. pp 21 – 27.

Walker SE (2007) The importance of sex hormones in systemic lupus erythematosus. In: Wallace DJ, Hahn BH Eds. Duboi’s lupus erythematosus. 7th ed. Philadelphia, Lippincott William and Wilkins. pp 273 – 281.

Rus V, Maury EE, Hochberg MC (2007) The epidemiology of systemic lupus erythematosus. In: Wallace DJ, Hahn BH Eds. Duboi’s lupus erythematosus. 7th ed. Philadelphia, Lippincott William and Wilkins. pp 34 – 42.

Tsokos GC (2011) Systemic lupus erythematosus. The New England Journal of Medicine 365 (22): 2110 – 2121. doi: 10.1056/NEJMra1100359.

National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. American Journal of Kidney Diseases 39 (2 Suppl 1): 1 – 266.

Iriane VM (2015) Analisis kadar transforming growth factor beta 1 Urine (uTGF-B1) dan rasio protein/kreatinin urine sebagai petanda biologi diagnosis nefritis lupus. Doctoral Thesis. Universitas Brawijaya

Kurts C, Panzer U, Anders HJ, Rees AJ (2013) The immune system and kidney disease: basic concepts and clinical implications. Nature Reviews Immunology 13 (10): 738 – 753. doi: 10.1038/nri3523.

Su CF, Chen YC, Chen HH et al. (1997) Mesangial lupus nephritis (WHO Class II) with associated nephritic syndrome: A case report and review the literature.

Linnik MD, Hu JZ, Heilbrunn KR et al. (2005) Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus. Arthritis and Rheumatology 52 (4): 1129 – 1137. doi: 10.1002/art.20980.

Arbuckle MR, McClain MT, Rubertone MV et al. (2003) Development of autoantibodies before the clinical onset of systemic lupus erythematosus. The New England Journal of Medicine 349 (16): 1526 – 1533. doi: 10.1056/NEJMoa021933.

Yung S, Chan TM (2015) Mechanisms of kidney injury in lupus nephritis – the role of anti-dsDNA Antibodies. Frontiers in Immunology 6: 475. doi: 10.3389/fimmu.2015.00475. eCollection 2015.

Fenton K, Fismen S, Hedberg A et al. (2009) Anti-dsDNA antibodies promote initiation and acquired loss of renal dnase1 promotes progression of lupus nephritis in autoimmune (NZBxNZW)F1 Mice. PLoS ONE 4 (12): e8474. doi: 10.1371/journal.pone.0008474.

Downloads

Published

2018-09-07

Issue

Vol. 8 No. 3 (2018)

Section

Articles

License

The work has not been published before (except in the form of an abstract or part of a published lecture or thesis) and it is not under consideration for publication elsewhere. When the manuscript is accepted for publication in this journal, the authors agree to automatic transfer of the copyright to the publisher.

Creative Commons License
Journal of Tropical Life Science is licensed under Creative Commons Attribution-NonCommercial 4.0 International License