Skip to main content
Erschienen in: Clinical Rheumatology 3/2021

18.08.2020 | Original Article

Urinary soluble CD163 is a good biomarker for renal disease activity in lupus nephritis

verfasst von: Ranjan Gupta, Akhilesh Yadav, Amita Aggarwal

Erschienen in: Clinical Rheumatology | Ausgabe 3/2021

Einloggen, um Zugang zu erhalten

Abstract

Objectives

Activated macrophages expressing CD163 (M2) are the most abundant macrophage subtype in renal biopsies from lupus nephritis (LN) patients. We studied the role of proteolytically cleaved soluble CD163 (sCD163) as a biomarker of LN disease activity.

Methods

SLE patients were classified as active LN (AN), inactive disease (ID), and active non-renal disease (ANR). Urine and plasma samples were collected at baseline from all patients and at 3 monthly follow-up from AN patients. sCD163 was measured by ELISA. Urine values were normalized to urinary creatinine excretion and expressed as pg/mg. Urine samples from 25 healthy controls (HC) and 20 rheumatoid arthritis patients served as disease controls (DC).

Results

Among the 122 patients studied (114 females, 57 AN, 42 ID, 23 ANR), baseline median urinary sCD163 in the AN group (114.01 pg/mg) was significantly higher (p < 0.001) as compared with ID (10.34 pg/mg), ANR (3.82 pg/mg), HC (0 pg/mg), and DC (7.56 pg/mg) groups and showed modest correlation with renal SLEDAI (r = 0.47; p < 0.001). Urinary sCD163 performed the best on receiver operating characteristics (ROC) analysis (AUC = 0.76) at baseline to differentiate between AN and ANR as compared with plasma sCD163, anti-ds DNA antibodies, and C3 and C4.
In follow-up study, urinary sCD163 decreased significantly (p < 0.001) in AN patients at 3 (22.07 pg/mg), 6 (12.7 pg/mg), 9 (11.09 pg/mg), and 12 months (7.2 pg/mg). In 4 patients who had either relapse or developed CKD, urinary sCD163 levels correlated with the changing disease activity.

Conclusions

Urinary sCD163 is a good biomarker of LN disease activity.
Key Points
Urinary sCD163 levels are raised in patients with active lupus nephritis and correlate with renal SLEDAI.
Urinary sCD163 levels fall after treatment and may be helpful in monitoring response to therapy in lupus nephritis.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Misra R, Gupta R (2009) Biomarkers in lupus nephritis. Int J Rheum Dis 18:219–232CrossRef Misra R, Gupta R (2009) Biomarkers in lupus nephritis. Int J Rheum Dis 18:219–232CrossRef
2.
Zurück zum Zitat Kopetschke K, Klocke J, Grießbach AS et al (2015) The cellular signature of urinary immune cells in lupus nephritis: new insights into potential biomarkers. Arthritis Res Ther 17:94CrossRef Kopetschke K, Klocke J, Grießbach AS et al (2015) The cellular signature of urinary immune cells in lupus nephritis: new insights into potential biomarkers. Arthritis Res Ther 17:94CrossRef
3.
Zurück zum Zitat Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C (2016) CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis. Arthritis Res Ther 18:–90 Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C (2016) CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis. Arthritis Res Ther 18:–90
4.
Zurück zum Zitat Bhattacharya S, Aggarwal A (2019) M2 macrophages and their role in rheumatic diseases. Rheumatol Int 39:769–780CrossRef Bhattacharya S, Aggarwal A (2019) M2 macrophages and their role in rheumatic diseases. Rheumatol Int 39:769–780CrossRef
5.
Zurück zum Zitat Kishimoto D, Kirino Y, Tamura M et al (2018) Dysregulated heme oxygenase-1low M2-like macrophages augment lupus nephritis via Bach1 induced by type I interferons. Arthritis Res Ther 20:64CrossRef Kishimoto D, Kirino Y, Tamura M et al (2018) Dysregulated heme oxygenase-1low M2-like macrophages augment lupus nephritis via Bach1 induced by type I interferons. Arthritis Res Ther 20:64CrossRef
6.
Zurück zum Zitat O’Reilly VP, Wong L, Kennedy C et al (2016) Urinary soluble CD163 in active renal vasculitis. J Am Soc Nephrol 27:2906–2916CrossRef O’Reilly VP, Wong L, Kennedy C et al (2016) Urinary soluble CD163 in active renal vasculitis. J Am Soc Nephrol 27:2906–2916CrossRef
7.
Zurück zum Zitat Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725CrossRef Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725CrossRef
8.
Zurück zum Zitat Gladman DD, Ibañez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed Gladman DD, Ibañez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed
9.
Zurück zum Zitat Hahn BH, McMahon MA, Wilkinson A et al (2012) American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 64:797–808CrossRef Hahn BH, McMahon MA, Wilkinson A et al (2012) American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 64:797–808CrossRef
10.
Zurück zum Zitat The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials. Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria. (2006) Arthritis Rheum 54:421–32 The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials. Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria. (2006) Arthritis Rheum 54:421–32
11.
Zurück zum Zitat Ma C, Xia Y, Yang Q, Zhao Y (2019) The contribution of macrophages to systemic lupus erythematosus. Clin Immunol 207:1–9CrossRef Ma C, Xia Y, Yang Q, Zhao Y (2019) The contribution of macrophages to systemic lupus erythematosus. Clin Immunol 207:1–9CrossRef
12.
Zurück zum Zitat Nakayama W, Jinnin M, Makino K et al (2012) CD163 expression is increased in the involved skin and sera of patients with systemic lupus erythematosus. Eur J Dermatol 22:512–517CrossRef Nakayama W, Jinnin M, Makino K et al (2012) CD163 expression is increased in the involved skin and sera of patients with systemic lupus erythematosus. Eur J Dermatol 22:512–517CrossRef
13.
Zurück zum Zitat Nishino A, Katsumata Y, Kawasumi H, Hirahara S, Kawaguchi Y, Yamanaka H (2019) Usefulness of soluble CD163 as a biomarker for macrophage activation syndrome associated with systemic lupus erythematosus. Lupus 986–994 Nishino A, Katsumata Y, Kawasumi H, Hirahara S, Kawaguchi Y, Yamanaka H (2019) Usefulness of soluble CD163 as a biomarker for macrophage activation syndrome associated with systemic lupus erythematosus. Lupus 986–994
14.
Zurück zum Zitat Zizzo G, Guerrieri J, Dittman LM, Merrill JT, Cohen PL (2013) Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity. Arthritis Res Ther 15(6):R212CrossRef Zizzo G, Guerrieri J, Dittman LM, Merrill JT, Cohen PL (2013) Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity. Arthritis Res Ther 15(6):R212CrossRef
15.
Zurück zum Zitat Zhu H, Sun X, Zhu L, Hu F, Shi L, Li Z, Su Y (2014) The expression and clinical significance of different forms of Mer receptor tyrosine kinase in systemic lupus erythematosus. J Immunol Res 2014:431896CrossRef Zhu H, Sun X, Zhu L, Hu F, Shi L, Li Z, Su Y (2014) The expression and clinical significance of different forms of Mer receptor tyrosine kinase in systemic lupus erythematosus. J Immunol Res 2014:431896CrossRef
16.
Zurück zum Zitat Li J, Liu CH, Xu DL, Gao B (2015) Significance of CD163-positive macrophages in proliferative glomerulonephritis. Am J Med Sci 350:387–392CrossRef Li J, Liu CH, Xu DL, Gao B (2015) Significance of CD163-positive macrophages in proliferative glomerulonephritis. Am J Med Sci 350:387–392CrossRef
17.
Zurück zum Zitat Endo N, Tsuboi N, Furuhashi K, Shi Y, du Q, Abe T, Hori M, Imaizumi T, Kim H, Katsuno T, Ozaki T, Kosugi T, Matsuo S, Maruyama S (2016) Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis. Nephrol Dial Transplant 31:2023–2033CrossRef Endo N, Tsuboi N, Furuhashi K, Shi Y, du Q, Abe T, Hori M, Imaizumi T, Kim H, Katsuno T, Ozaki T, Kosugi T, Matsuo S, Maruyama S (2016) Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis. Nephrol Dial Transplant 31:2023–2033CrossRef
18.
Zurück zum Zitat Gupta R, Yadav A, Aggarwal A (2016) Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity. Clin Rheumatol 35(11):2707–2714CrossRef Gupta R, Yadav A, Aggarwal A (2016) Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity. Clin Rheumatol 35(11):2707–2714CrossRef
19.
Zurück zum Zitat Dekkema GJ, Abdulahad WH, Bijma T, Moran SM, Ryan L, Little MA, Stegeman CA, Heeringa P, Sanders JSF (2019) Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study. Nephrol Dial Transplant 34:234–242CrossRef Dekkema GJ, Abdulahad WH, Bijma T, Moran SM, Ryan L, Little MA, Stegeman CA, Heeringa P, Sanders JSF (2019) Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study. Nephrol Dial Transplant 34:234–242CrossRef
20.
Zurück zum Zitat Gupta R, Yadav A, Misra R, Aggarwal A (2015) Urinary sCD25 as a biomarker of lupus nephritis disease activity. Lupus 24:273–279CrossRef Gupta R, Yadav A, Misra R, Aggarwal A (2015) Urinary sCD25 as a biomarker of lupus nephritis disease activity. Lupus 24:273–279CrossRef
21.
Zurück zum Zitat Phatak S, Chaurasia S, Mishra SK, Gupta R, Agrawal V, Aggarwal A, Misra R (2017) Urinary B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL): potential biomarkers of active lupus nephritis. Clin Exp Immunol 187:376–382CrossRef Phatak S, Chaurasia S, Mishra SK, Gupta R, Agrawal V, Aggarwal A, Misra R (2017) Urinary B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL): potential biomarkers of active lupus nephritis. Clin Exp Immunol 187:376–382CrossRef
22.
Zurück zum Zitat Moran SM, Monach PA, Zgaga L et al (2020) 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 35(2):283–291PubMed Moran SM, Monach PA, Zgaga L et al (2020) 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 35(2):283–291PubMed
23.
Zurück zum Zitat Lu J, Cao Q, Zheng D, Sun Y, Wang C, Yu X, Wang Y, Lee VWS, Zheng G, Tan TK, Wang X, Alexander SI, Harris DCH, Wang Y (2013) Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease. Kidney Int 84:745–755CrossRef Lu J, Cao Q, Zheng D, Sun Y, Wang C, Yu X, Wang Y, Lee VWS, Zheng G, Tan TK, Wang X, Alexander SI, Harris DCH, Wang Y (2013) Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease. Kidney Int 84:745–755CrossRef
Metadaten
Titel
Urinary soluble CD163 is a good biomarker for renal disease activity in lupus nephritis
verfasst von
Ranjan Gupta
Akhilesh Yadav
Amita Aggarwal
Publikationsdatum
18.08.2020
Verlag
Springer International Publishing
Erschienen in
Clinical Rheumatology / Ausgabe 3/2021
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-020-05343-6

Weitere Artikel der Ausgabe 3/2021

Clinical Rheumatology 3/2021 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.