Promising urinary biomarkers of glomerulonephritis in systemic lupus erythematosus and ANCA-associated vasculitides

Systemic lupus erythematosus (SLE) and systemic vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA-associated vasculitides, AAV) are severe chronic autoimmune diseases with multisystem involvement. Despite substantial differences in pathogenesis, they share frequent and prognostically unfavorable kidney involvement, which largely determines the course and outcome of the disease. The use of the classic invasive method for dynamic assessment of renal pathology – percutaneous kidney biopsy – has serious limitations. Therefore, the search for noninvasive biomarkers that allow evaluation of glomerulonephritis activity becomes particularly relevant. For this purpose, in particular, monocyte chemoattractant protein 1 (MCP1/CCL2), soluble CD163 receptor (sCD163), integrin CD11b, calprotectin, and others may be used. Such “liquid biopsy” components of the kidney may have significant diagnostic and prognostic value in SLE and AAV.

1. Moiseev SV, Bulanov NM. Acute or progressive deterioration of kidney function in immunoinflammatory rheumatic diseases. Klinicheskaya farmakologiya i terapiya. 2023;32(1):4-13. (In Russ.).

2. Bobrova LA, Kozlovskaya NL. Lupus nephritis and thrombotic microangiopathy. Terapevticheskii arkhiv. 2024;96(6):628-634. (In Russ.).

3. Kaul A, Gordon C, Crow MK, et al. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016 Jun 16:2:16039. doi: 10.1038/nrdp.2016.39.

4. Kitching AR, Anders HJ, Basu N, et al. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020 Aug 27;6(1):71. doi: 10.1038/s41572-020-0204-y.

5. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011 Dec 1;365(22):2110-21. doi: 10.1056/NEJMra1100359.

6. Nasonov EL, editor. Systemic lupus erythematosus. In: Russian clinical guidelines. Rheumatology. Moscow: GEOTAR-Media; 2017. P. 113-127.

7. Aseeva EA, Solov'ev SK, Pletnev EA, Datsina AV. 2024 ACR guidelines on screening, treatment, and management of patients with lupus nephritis. Modern Rheumatology Journal. 2025;19(3):27-32. (In Russ.). doi: 10.14412/1996-7012-2025-3-27-32.

8. Hanly JG, O’Keeffe AG, Su L, et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology (Oxford). 2016 Feb; 55(2):252-62. doi: 10.1093/rheumatology/kev311.

9. Bobkova IN, Moiseev SV, Lysenko LV, Kamyshova ES. Lupus nephritis in the 21st century. Terapevticheskii arkhiv. 2022;94(6): 713-717. (In Russ.).

10. Tektonidou MG, Dasgupta A, Ward MM. Risk of End-Stage Renal Disease in Patients with Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis. Arthritis Rheumatol. 2016 Jun;68(6):1432-41. doi: 10.1002/art.39594.

11. Tian J, Zhang D, Yao X, et al. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis. 2023 Mar;82(3): 351-356. doi: 10.1136/ard-2022-223035.

12. Roveta A, Parodi EL, Brezzi B, et al. Lupus Nephritis from Pathogenesis to New Therapies: An Update. Int J Mol Sci. 2024 Aug 18;25(16):8981. doi: 10.3390/ijms25168981.

13. Parikh SV, Almaani S, Brodsky S, Rovin BH. Update on Lupus Nephritis: Core Curriculum 2020. Am J Kidney Dis. 2020 Aug; 76(2):265-281. doi: 10.1053/j.ajkd.2019.10.017.

14. Pisetsky DS. Unique Interplay Between Antinuclear Antibodies and Nuclear Molecules in the Pathogenesis of Systemic Lupus Erythematosus. Arthritis Rheumatol. 2024 Sep; 76(9):1334-1343. doi: 10.1002/art.42863.

15. Bruschi M, Angeletti A, Prunotto M, et al. A Critical View on Autoantibodies in Lupus Nephritis: Concrete Knowledge Based on Evidence. Autoimmun Rev. 2024 May;23(5): 103535. doi: 10.1016/j.autrev.2024.103535.

16. Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004 Feb;65(2):521-30. doi: 10.1111/j.1523-1755.2004.00443.x.

17. Clinical Practice guidelines for the management of lupus nephritis. Nefrologiya i dializ. Prilozhenie. 2024;26(2):1-67. (In Russ.).

18. Bulanov NM, Zakharova EV, Kozlovskaya NL, et al. Draft proactive clinical guidelines for the diagnosis and treatment of kidney damage in ANCA-associated vasculitis. Nefrologiya i dializ. 2025;27(2):116-166. (In Russ.).

19. Sharma A, Naidu GSRSNK, Rathi M, et al. Clinical features and long term outcomes of 105 granulomatosis with polyangiitis patients: a single centre experience from north India. Int J Rheum Dis. 2018 Jan;21(1): 278-284. doi: 10.1111/1756-185X.13071.

20. Couser WG. Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis. 1988 Jun;11(6):449-64. doi: 10.1016/s0272-6386(88)80079-9.

21. Ferrario F, Rastaldi MP. Pathology of rapidly progressive glomerulonephritis. Oxford University Press; 1998. P. 59-107.

22. Joh K, Muso E, Shigematsu H, et al. Renal pathology of ANCA-related vasculitis: proposal for standardization of pathological diagnosis in Japan. Clin Exp Nephrol. 2008 Aug; 12(4):277-291. doi: 10.1007/s10157-008-0052-7.

23. Berden E, Ferrario F, Hagen EC, et al. Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol. 2010 Oct;21(10):1628-36. doi: 10.1681/ASN.2010050477.

24. Kessenbrock K, Krumbholz M, Schönermarck U, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009 Jun;15(6):623-5. doi: 10.1038/nm.1959.

25. Xiao H, Schreiber A, Heeringa P, et al. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol. 2007 Jan;170(1):52-64. doi: 10.2353/ajpath.2007.060573.

26. Schreiber A, Xiao H, Jennette JC, et al. C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J Am Soc Nephrol. 2009 Feb;20(2):289-98. doi: 10.1681/ASN.2008050497.

27. Wilhelmus S, Alpers CE, Cook HT, et al. The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic Lesions. J Am Soc Nephrol. 2015 Dec;26(12): 2938-46. doi: 10.1681/ASN.2015040384.

28. Floege J, Jayne DRW, Sanders JSF, et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis. Kidney Int. 2024 Mar;105(3):447-449. doi: 10.1016/j.kint.2023.10.009.

29. Rhee RL, Davis JC, Ding L. The utility of urinalysis in determining the risk of renal relapse in ANCA-associated vasculitis. Clin J Am Soc Nephrol. 2018 Feb 7;13(2):251-257. doi: 10.2215/CJN.04160417.

30. O'Reilly VP, Wong L, Kennedy C, et al. Urinary soluble CD163 in active renal vasculitis. J Am Soc Nephrol. 2016 Sep;27(9):2906- 16. doi: 10.1681/ASN.2015050511.

31. Chebotareva NV, Bobkova IN, Kozlovskaya LV, et al. Determination of urinary excretion of monocytic chemotactic protein-1 and transforming growth factor-β1 in patients with chronic glomerulonephritis as a method for assessing the processes of fibrogenesis in the kidney. Klinicheskaya nefrologiya. 2010;(3): 49-55. (In Russ.).

32. Nasonov EL, Avdeeva AS, Baranov AA, Samsonov MYu. Serum calprotectin in immunoinflammatory rheumatic diseases: a new biomarker of inflammation. Nauchno-prakticheskaya revmatologiya. 2025;63(5):432-442. (In Russ.).

33. Rovin BH, Song H, Birmingham DJ, et al. Urine chemokines as biomarkers of human systemic lupus erythematosus activity. J Am Soc Nephrol. 2005 Feb;16(2):467-73. doi: 10.1681/ASN.2004080658.

34. Hou L, Koutsogiannaki S, Yuki K. Multifaceted, unique role of CD11c in leukocyte biology. Front Immunol. 2025 Mar 4:16:1556992. doi: 10.3389/fimmu.2025.1556992. eCollection 2025.

35. Yokoe Y, Tsuboi N, Imaizumi T, et al. Clinical impact of urinary CD11b and CD163 on the renal outcomes of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. Nephrol Dial Transplant. 2021 Jul 23;36(8):1452-1463. doi: 10.1093/ndt/gfaa097.

36. Kitagawa A, Tsuboi N, Yokoe Y, et al. Urinary levels of the leukocyte surface molecule CD11b associate with glomerular inflammation in lupus nephritis. Kidney Int. 2019 Mar; 95(3):680-692. doi: 10.1016/j.kint.2018.10.025.

37. Stevanin M, Busso N, Chobaz V, et al. CD11b regulates the Treg/Th17 balance in murine arthritis via IL-6. Eur J Immunol. 2017 Apr;47(4):637-645. doi: 10.1002/eji.201646565.

38. Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of the haemoglobin scavenger receptor. Nature. 2001 Jan 11;409(6817): 198-201. doi: 10.1038/35051594.

39. Etzerodt A, Moestrup SK. CD163 and inflammation: Biological, diagnostic, and therapeutic aspects. Antioxid Redox Signal. 2013 Jun 10;18(17):2352-63. doi: 10.1089/ars.2012.4834.

40. Moran SM, Monach PA, Zgaga L, et al. Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrol Dial Transplant. 2020 Feb 1;35(2): 283-291. doi: 10.1093/ndt/gfy300.

41. Zhao L, David MZ, Hyjek E, et al. M2 macrophage infiltrates in the early stages of ANCA-associated pauci-immune necrotizing GN. Clin J Am Soc Nephrol. 2015 Jan 7;10(1): 54-62. doi: 10.2215/CJN.03230314.

42. Nielsen MC, Andersen МN, Rittiget N, et al. The macrophage-related biomarkers sCD163 and sCD206 are released by different shedding mechanisms. J Leukoc Biol. 2019 Nov;106(5):1129-1138. doi: 10.1002/JLB.3A1218-500R.

43. Fava А, Buyon J, Magder L, et al. Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis. JCI Insight. 2024 Jan 23; 9(2):e172569. doi: 10.1172/jci.insight.172569.

44. Egorova ON, Datsina AV, Tarasova GM, et al. Clinical significance of urinary soluble CD11b and CD163 receptor levels in ANCA-associated vasculitides. Modern Rheumatology Journal. 2025;19(5):26-33. (In Russ.). doi: 10.14412/1996-7012-2025-5-26-33.

45. Akhmed ES, Eldin KRA, El'maksud AKhA, Ali SS. Assessment of CD163 levels in urine as a biomarker for the diagnosis of lupus nephritis. Meditsinskaya immunologiya. 2025;27(2): 335-342. (In Russ.).

46. Stern E, Hong C, Ong VH, et al. Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a potential local marker of renal involvement in scleroderma [abstract]. J Interferon Cytokine Res. 2009 Jun;29(6):313-26. doi: 10.1089/jir.2008.0027.

47. Pepper RJ, Hamour S, Chavele KM, et al. Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and glomerulonephritis. Kidney Int. 2013 Jun;83(6):1150-8. doi: 10.1038/ki.2013.2.

48. Vorkel' EN, Reshetnyak TM, Nurbaeva KS, et al. Serum calprotectin in vasculitis associated with antineutrophil cytoplasmic antibodies. Modern Rheumatology Journal. 2024;18(4): 66-73. (In Russ.). doi: 10.14412/1996-7012-2024-4-66-73.

49. Heller F, Frischmann S, Grünbaum M, et al. Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury. Clin J Am Soc Nephrol. 2011 Oct;6(10): 2347-55. doi: 10.2215/CJN.02490311.

50. Hiramoto K, Saito S, Hanaoka H, et al. Urinary Biomarkers Associated With Pathogenic Pathways Reflecting Histologic Findings in Lupus Nephritis. Arthritis Rheumatol. 2025 Mar;77(3):298-310. doi: 10.1002/art.43017.

51. Inoue K. Pentraxin 3. Rinsho Byori. 2011 Jul;59(7):694-701.

52. Jonasdottir AD, Antovic A, Qureshi AR, et al. Pentraxin-3 – a potential biomarker in ANCA-associated vasculitis. Scand J Rheumatol. 2023 May;52(3):293-301. doi: 10.1080/03009742.2022.2045790.

53. Pang Y, Tan Y, Li Y, et al. Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis: A Large Multicenter Cross-Sectional Study. Medicine (Baltimore). 2016 Jan;95(3):e2520. doi: 10.1097/MD.0000000000002520.

54. Gou SJ, Yuan J, Chen M, et al. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2013 Jan;83(1): 129-37. doi: 10.1038/ki.2012.313.

55. Jayne D, Bruchfeld A, Harper L, et al. Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis. J Am Soc Nephrol. 2017 Sep;28(9):2756-2767. doi: 10.1681/ASN.2016111179.

56. van Timmeren MM, van den Heuvel MC, Bailly V, et al. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol. 2007 Jun;212(2):209-17. doi: 10.1002/path.2175.

57. Brunner HI, Bennett MR, Mina R, et al. Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis. Arthritis Rheum. 2012 Aug; 64(8):2687-97. doi: 10.1002/art.34426.

58. Kishi F, Nagai K, Takamatsu N, et al. Urinary type IV collagen excretion is involved in the decline in estimated glomerular filtration rate in the Japanese general population without diabetes: A 5-year observational study. PLoS One. 2018 Apr 6;13(4):e0195523. doi: 10.1371/journal.pone.0195523.