COMPARISON URINE NEUTROPHIL GELATINASE – ASSOCIATED LIPOCALIN WITH STANDARD PARAMETERS IN MONITORING ACTIVITY LUPUS NEPHRITIS - CLASS IV
Abstract
Introduction: Lupus nephritis (LN) is one of the most serious complications in the development of systemic lupus erythematosus, that can adversely affect the course and prognosis of this autoimmune disease. Therefore, monitoring the effect of applied therapy, achieving remission, or monitoring LN activity is still a great challenge for nephrologists. This study aimed to compare the urinary neutrophile gelatinase associated lipocalin (u/NGAL) with traditionally accepted parameters for LN activity to indicate the importance of its determination in these patients.
Methods: The study group consisted of 40 patients, who were prospectively followed for a period of 4 months within three control visits to 2 months. The first group (20/40) had active LN (Group A), and the second group had LN in remission (Group B). The parameters were compared: proteins/s, albumins/s, C3, C4, anti-ds-DNA Ab, proteinuria 24h, ur.protein / creatinine ratio - Up / cre, u/NGAL (immunochemical method CMIA),GFR.
Results: Comparing standard parameters of disease activity and NGAL/u between groups, a statistically significant difference was obtained (p <0.001). Within Group A, comparing the parameters (X ± SD) by visits (0 : 2) for anti-ds-DNA Ab a significance of p <0.05 was obtained, for albumin / s and C3 a significance of p <0.01 was obtained, and proteinuria / 24h, Upr / Cre, u/NGAL had a significance of p <0.001. The negative correlation of u/NGAL was statistically significant at initial visit with albumin/s (p <0.01) as well as the positive correlation with proteinuria 24h and Up / cre (p <0.001). In visit 2 significant negative correlation of u/NGAL with albumin /s and C3 p <0.05, and positive correlation with anti-ds-DNA Ab, proteinuria 24h and Up/cre p <0.001.
Conclusion: In our study, the biomarker u/NGAL, showed a statistically significant correlation with traditional parameters of lupus nephritis activity, and its determination could be significant in monitoring LN activity and monitoring responses to applied treatment.
References
1. Morales E, Galindo M, Trujillo H, Praga M. Update on Lupus Nephritis: Looking for a New Vision. Nephron 2021; 145:1–13.
2. Hsieh YP, Wen YK, Chen ML.The value of early renal biopsy in systemic lupus erythematosus patients presenting with renal involvement.Clin Nephrol 2012;77(1):18-24.
3. Christopher-Stine L, Siedner M, Lin J, Haas M, Parekh H, Petri M, Fine DM. Renal biopsy in lupus patients with low levels of proteinuria. J Rheumatol 2007;34(2):332-5.
4. Kanno A, Hotta O, Yusa N, Taguma Y.Predictive Factors of Clinical Outcome in Patients with Diffuse Proliferative Lupus Nephritis Treated Early by Intravenous Methylprednisolone Pulse Therapy. Renal Failure 2007; 29(1): 41-7.
5. ChenTK, EstrellaMM,FineDM.Predictors of kidney biopsy complication among patients with systemic lupus erythematosus. Lupus 2012 ; 21 (8) : 848-54.
6.Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25:1271-7.
7. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725.
8. Churg J, Bernstein J, Glassock RJ. Lupus nephritis. En: Classification and Atlas of Glomerular Disease, 2nd ed. New York, Igaku-Shoin, 1995, p51.
9. Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB et al.The classification of glomerulonephritis in systemic lupus erithematous revisited. J Am Soc Nephrol 2004; 15:241-250.
10. Austin HA 3rd, Muenz LR, Joyce KM, Antonovych TT, Balow JE: Diffuse proliferative lupus nephritis: Identification of specific pathologic features affecting renal outcome. Kidney Int 1984; 25: 689–95.
11. Gladman DD, Ibañez D, Urowltz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002;29(2):288–91.
12. Uttenthal LO. NGAL: a marker molecule for the distressed kidney? Clin Lab Internat 2005; 29(7): 39-41.
13. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 2002; 10: 1033-43.
14. Zhang CF, Wang HJ , Tong ZH, Zhang C, Wang ZS, Yang HQ, et al. The diagnostic and prognostic values of serum and urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in sepsis induced acute renal injury patients. Eur Rev Med Pharmacol Sci 2020;24(10):5604-17.
15. Parikh CR, Coca SG, Thiessen-Philbrook H, Shlipak MG, Koyner JL, Wang Z et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol 2011; 22(9):1748-57.
16. Ralib АМ, Pickering ЈW, Shaw GM, Devarajan P, Edelstein CL, Bonventre JV et al. Test Characteristics of Urinary Biomarkers Depend on Quantitation Method in Acute Kidney Injury . J Am Soc Nephrol 2012 ; 23: 322–33.
17. Zhou F, Luo Q, Wang L, Han L. Diagnostic value of neutrophil gelatinase-associated lipocalin for early diagnosis of cardiac surgery-associated acute kidney injury: a meta-analysis.. Eur J Cardiothorac Surg 2016;49(3):746-55.
18. Wagener G, Gubitosa G, Wang S , Borregaard N, Kim M, Lee HT. Increased incidence of acute kidney injury with aprotinin use during cardiac surgery detected with urinary NGAL. Am J Nephrol 2008; 28(4):576-82.
19. Devarajan P. Neutrophil gelatinase-associated lipocalin—an emerging troponin for kidney injury. Nephrol Dial Transplant 2008; 23 (12): 3737–43.
20. Dent C, Ma Q, Dastrala S, Bennett M, Mitsnefes M. Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Critical Care 2007; 11: R127.
21. Banai A, Rozenfeld KL, Lewit D, Merdler I, Loewenstein I, Banai S, Shacham Y. Neutrophil gelatinase-associated lipocalin (NGAL) for the prediction of acute kidney injury in chronic kidney disease patients treated with primary percutaneous coronary intervention. Int J Cardiol Heart Vasc 2020 ; 32:100695.
22. Bolignano D, Lacquaniti A, Coppolino G, Campo S, Arena , Buemi M. Neutrophil gelatinase-associated lipocalin reflects the severity of renal impairment in subjects affected by chronic kidney disease. Kidney Blood Press Research 2008; 31(4):255–8.
23. Hinze CH, Suzuki M, Klein-Gitelman M, Passo MH, Olson J, Singer NG et al. Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis Rheum 2009; 60(9):2772-81.
24. Rubinstein T, Pitashny M, Putterman C. The novel role of neutrophil gelatinase-B associated lipocalin (NGAL)/Lipocalin-2 as a biomarker for lupus nephritis. Autoimmun Rev 2008 ;7(3):229-34.
25. Qing X, Zavadil J, Crosby MB, Hogarth MP, Hahn BH, Mohan C, et al. Nephritogenic anti- DNA antibodies regulate gene expression in MRL/lpr mouse glomerular mesangial cells. Arth Rheum 2006; 54(7):2198–2210.
26. Suzuki М, Wiers КМ , Klein-Gitelman МS , Haines KA, Olson J, Onel KB, et al.Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis. Pediatric Nephrology 2008; 23(3): 403-12.
27. Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, et al.l. Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 2006; 54 (8) : 2577–84.
28. Koura HM, Galal A, Manal F. Elshamaa FM, Kandil MD, Elghorori AE, et al. Urinary neutrophil gelatinase –associated lipokalin as a marker of disease activity in patients with lupus nephritis . Int J Acad Reasrch 2011; 3 (1): 141-6.
29. Yang CC, Hsieh SC, Li KJ, Wu CH, Lu MC, Tsai CY et al. Urinary Neutrophil Gelatinase-Associated Lipocalin Is a Potential Biomarker for Renal Damage in Patients with Systemic Lupus Erythematosus . J Biomed Biotechnol 2012; 2012: 759313.
30. Rubinstein T, Pitashny M, Levine B, Schwartz N, Schwartzman J, Weinstein E, et al. Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis. Rheumatology 2010 ;49: 960–71.
31. Gao Y, Wang B, Cao J, Feng S, Liu B. Elevated Urinary Neutrophil Gelatinase-Associated Lipocalin Is a Biomarker for Lupus Nephritis: A Systematic Review and Meta-Analysis. Biomed Res Int 2020; 2020: 2768326.
32. El-Mohsen MA, Tawfik A, Bichari W, Shawky S, Mady G, Hassan M. Value of Urinary Neutrophil Gelatinase-Associated Lipocalin versus Conventional Biomarkers in Predicting Response to Treatment of Active Lupus Nephritis. Int J Nephrol 2020 ; 2020: 8855614.
Copyright (c) 2022 Dr sc. med. Violeta Rabrenović, Milica Petrović, Milorad Rabrenović
This work is licensed under a Creative Commons Attribution 4.0 International License.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.