Clinical impact of urinary CD11b and CD163 on the renal outcomes of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis

Yuki Yokoe; Naotake Tsuboi; Takahiro Imaizumi; Akimitsu Kitagawa; Munetoshi Karasawa; Takaya Ozeki; Nobuhide Endo; Yuriko Sawa; Sawako Kato; Takayuki Katsuno; Shoichi Maruyama; Kunihiro Yamagata; Joichi Usui; Michio Nagata; Ken-Ei Sada; Hitoshi Sugiyama; Koichi Amano; Yoshihiro Arimura; Tatsuya Atsumi; Yukio Yuzawa; Hiroaki Dobashi; Yoshinari Takasaki; Masayoshi Harigai; Hitoshi Hasegawa; Hirofumi Makino; Seiichi Matsuo; Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis and for Intractable Renal Disease

doi:10.1093/ndt/gfaa097

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.

Authors

Yuki Yokoe^{1

2}, Naotake Tsuboi^{1

2}, Takahiro Imaizumi¹, Akimitsu Kitagawa¹, Munetoshi Karasawa¹, Takaya Ozeki¹, Nobuhide Endo¹, Yuriko Sawa¹, Sawako Kato¹, Takayuki Katsuno³, Shoichi Maruyama¹, Kunihiro Yamagata⁴, Joichi Usui⁴, Michio Nagata⁵, Ken-Ei Sada⁶, Hitoshi Sugiyama⁷, Koichi Amano⁸, Yoshihiro Arimura^{9

10}, Tatsuya Atsumi¹¹, Yukio Yuzawa², Hiroaki Dobashi¹², Yoshinari Takasaki¹³, Masayoshi Harigai^{14

15}, Hitoshi Hasegawa¹⁶, Hirofumi Makino¹⁷, Seiichi Matsuo¹⁸; Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis and for Intractable Renal Disease

Affiliations

¹ Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Department of Nephrology, Fujita Health University Graduate School of Medicine, Toyoake, Japan.
³ Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan.
⁴ Department of Nephrology, University of Tsukuba, Tsukuba, Japan.
⁵ Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
⁶ Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Okayama, Japan.
⁷ Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan.
⁸ Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
⁹ Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan.
¹⁰ Department of Internal Medicine, Kichijoji Asahi Hospital, Musashino, Japan.
¹¹ Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
¹² Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kita-gun, Japan.
¹³ Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
¹⁴ Department of Pharmacovigilance, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁵ Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
¹⁶ Department of Hematology, Clinical Immunology, and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Japan.
¹⁷ Okayama University, Okayama, Japan.
¹⁸ Nagoya University, Nagoya, Japan.

PMID: 32639002
DOI: 10.1093/ndt/gfaa097

Abstract

Background: The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN.

Methods: U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period.

Results: U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy.

Conclusions: Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.

Keywords: anti-neutrophil cytoplasmic antibody; biomarkers; inflammation; macrophages; neutrophils.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis*
Antibodies, Antineutrophil Cytoplasmic
Antigens, CD / urine*
Antigens, Differentiation, Myelomonocytic
CD11b Antigen
Glomerulonephritis* / diagnosis
Humans
Kidney
Receptors, Cell Surface

Substances

Antibodies, Antineutrophil Cytoplasmic
Antigens, CD
Antigens, Differentiation, Myelomonocytic
CD11b Antigen
CD163 antigen
ITGAM protein, human
Receptors, Cell Surface