Urinary CD163 is a Marker of Active Kidney Disease in Childhood-onset Lupus Nephritis

Overview

Journal Rheumatology (Oxford)

Publisher Oxford University Press

Specialty Rheumatology

Date 2022 Aug 12

PMID 35961024

Authors

Haleigh Inthavong

Kamala Vanarsa

Jessica Castillo

M John Hicks

Chandra Mohan

Scott E Wenderfer

Affiliations

Soon will be listed here.

Abstract

Objective: The objective of this study was to evaluate the utility of urine CD163 for detecting disease activity in childhood-onset SLE (cSLE) patients.

Methods: Sixty consecutive pediatric patients fulfilling four or more ACR criteria for SLE and 20 healthy controls were recruited for testing of urinary CD163 using ELISA. SLE disease activity was assessed using the SLEDAI-2K.

Results: Urine CD163 was significantly higher in patients with active LN than inactive SLE patients and healthy controls, with receiver operating characteristics area under the curve values ranging from 0.93 to 0.96. LN was ascertained by kidney biopsy. Levels of CD163 significantly correlated with the SLEDAI, renal SLEDAI, urinary protein excretion and C3 complement levels. Urine CD163 was also associated with high renal pathology activity index and chronicity index, correlating strongly with interstitial inflammation and interstitial fibrosis based on the examination of concurrent kidney biopsies.

Conclusion: Urine CD163 emerges as a promising marker for identifying cSLE patients with active kidney disease. Longitudinal studies are warranted to validate the clinical utility of urine CD163 in tracking kidney disease activity in children with lupus.

Citing Articles

Biomarkers for systemic lupus erythematosus: A scoping review.

Zhang S, Xu R, Kang L Immun Inflamm Dis. 2024; 12(10):e70022.

PMID: 39364719 PMC: 11450456. DOI: 10.1002/iid3.70022.

Prediction of treatment response in lupus nephritis using density of tubulointerstitial macrophage infiltration.

Wang J, Lou W, Zhu M, Tu Y, Chen D, Qiu D Front Immunol. 2024; 15:1321507.

PMID: 38415246 PMC: 10896899. DOI: 10.3389/fimmu.2024.1321507.

Lupus Nephritis Biomarkers: A Critical Review.

Alduraibi F, Tsokos G Int J Mol Sci. 2024; 25(2).

PMID: 38255879 PMC: 10815779. DOI: 10.3390/ijms25020805.

Lupus Nephritis in Children: Novel Perspectives.

Pennesi M, Benvenuto S Medicina (Kaunas). 2023; 59(10).

PMID: 37893559 PMC: 10607957. DOI: 10.3390/medicina59101841.

Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort.

Conticini E, Naveen R, Sen P, Singh M, Rathore U, Anuja A Front Med (Lausanne). 2023; 10:1127657.

PMID: 37425322 PMC: 10325640. DOI: 10.3389/fmed.2023.1127657.

References

Zhou D, Wang Y, Chen L, Zhang W, Luan J . Soluble CD163: A Novel Biomarker with Diagnostic and Therapeutic Implications in Autoimmune Diseases. J Rheumatol. 2016; 43(4):830. DOI: 10.3899/jrheum.151317. View

Bleesing J, Prada A, Siegel D, Villanueva J, Olson J, Ilowite N . The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis. Arthritis Rheum. 2007; 56(3):965-71. DOI: 10.1002/art.22416. View

Austin 3rd H, Muenz L, Joyce K, Antonovych T, Balow J . Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Int. 1984; 25(4):689-95. DOI: 10.1038/ki.1984.75. View

Zhang T, Li H, Vanarsa K, Gidley G, Mok C, Petri M . Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages. Front Immunol. 2020; 11:671. PMC: 7174755. DOI: 10.3389/fimmu.2020.00671. View

Gupta R, Yadav A, Aggarwal A . Urinary soluble CD163 is a good biomarker for renal disease activity in lupus nephritis. Clin Rheumatol. 2020; 40(3):941-948. DOI: 10.1007/s10067-020-05343-6. View

Hochberg M . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997; 40(9):1725. DOI: 10.1002/art.1780400928. View

Tucker L, Uribe A, Fernandez M, Vila L, McGwin G, Apte M . Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus. 2008; 17(4):314-22. PMC: 2818044. DOI: 10.1177/0961203307087875. View

Wenderfer S, Chang J, Goodwin Davies A, Luna I, Scobell R, Sears C . Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis: Development and Validation of Computable Phenotypes. Clin J Am Soc Nephrol. 2021; 17(1):65-74. PMC: 8763148. DOI: 10.2215/CJN.07810621. View

Mok C . Biomarkers for lupus nephritis: a critical appraisal. J Biomed Biotechnol. 2010; 2010:638413. PMC: 2857808. DOI: 10.1155/2010/638413. View

10.

Stichweh D, Arce E, Pascual V . Update on pediatric systemic lupus erythematosus. Curr Opin Rheumatol. 2004; 16(5):577-87. DOI: 10.1097/01.bor.0000137852.42270.0f. View

11.

Olmes G, Buttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C . CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis. Arthritis Res Ther. 2016; 18:90. PMC: 4835936. DOI: 10.1186/s13075-016-0989-y. View

12.

Zizzo G, Guerrieri J, Dittman L, Merrill J, Cohen P . Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity. Arthritis Res Ther. 2013; 15(6):R212. PMC: 3978923. DOI: 10.1186/ar4407. View

13.

Brunner H, Gladman D, Ibanez D, Urowitz M, Silverman E . Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008; 58(2):556-62. DOI: 10.1002/art.23204. View

14.

Van Gorp H, Delputte P, Nauwynck H . Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy. Mol Immunol. 2010; 47(7-8):1650-60. DOI: 10.1016/j.molimm.2010.02.008. View

15.

Yang G, Guo N, Yin J, Wu J . Elevated soluble CD163 predicts renal function deterioration in lupus nephritis: a cohort study in Eastern China. J Int Med Res. 2021; 49(11):3000605211049963. PMC: 8586176. DOI: 10.1177/03000605211049963. View

16.

Brunner H, Mueller M, Rutherford C, Passo M, Witte D, Grom A . Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum. 2006; 54(8):2577-84. DOI: 10.1002/art.22008. View

17.

Nakayama W, Jinnin M, Makino K, Kajihara I, Makino T, Fukushima S . CD163 expression is increased in the involved skin and sera of patients with systemic lupus erythematosus. Eur J Dermatol. 2012; 22(4):512-7. DOI: 10.1684/ejd.2012.1756. View

18.

Mok C, Mohan C . Urinary Biomarkers in Lupus Nephritis: Are We There Yet?. Arthritis Rheumatol. 2020; 73(2):194-196. DOI: 10.1002/art.41508. View

19.

Schwartz N, Michaelson J, Putterman C . Lipocalin-2, TWEAK, and other cytokines as urinary biomarkers for lupus nephritis. Ann N Y Acad Sci. 2007; 1109:265-74. DOI: 10.1196/annals.1398.032. View

20.

Hiramatsu N, Kuroiwa T, Ikeuchi H, Maeshima A, Kaneko Y, Hiromura K . 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). 2008; 47(5):702-7. DOI: 10.1093/rheumatology/ken019. View