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Abstract: SA-PO414

Urinary CD11b and CD163 Reflect Clinical and Histological Disease Activity in Renal Involvement of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitides

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Yokoe, Yuki, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Tsuboi, Naotake, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
Background

Glomerular leukocyte infiltration on histology reflects the renal inflammation in various forms of glomerulonephritis. Especially glomerular crescent formation, evidenced with robust extracapillary leukocyte and epithelial cell proliferation at the active stage, often present on glomerulonephritis complicated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), has been proposed as a significant indicator of the disease activity and prognosis. Both cell surface molecules of CD11b, an α subunit of leukocyte integrin Mac-1 expressed on neutrophils and monocytes/macrophages, and of CD163, a scavenger receptor expressed on macrophages, have been demonstrated their cleavage from leukocyte upon inflammation-related cell activation. In the present study, we investigated the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) as potential biomarkers for AAV.

Methods

We measured U-CD11b and U-CD163 by ELISA in AAV patient samples from the institutional (N-KDR; 61 patients at the diagnosis) and Japanese nation-wide (RemIT-JAV-RPGN; 138 at the diagnosis and 56 patients after 6 months treatment) cohorts, and evaluated those associations with clinical and histological parameters.

Results

Both U-CD11b and U-CD163 significantly correlated with renal score of Birmingham Vasculitis Activity Score (BVAS), and were particularly elevated in AAV patients classified in crescentic category by European Vasculitis Study Group (EUVAS) evaluation. Histological analysis for leukocyte profiles demonstrated significant association of U-CD11b levels with glomerular CD11b+ cell numbers both in endo- and extra-capillary. On the other hand, U-CD163 reflected glomerular CD163+ cells in extra-capillary. Significant reduction of U-CD163 (U-CD163; p<0.001, U-CD11b; p=0.26) was observed in identical AAV patients at 6 months following by the remission induction therapy.

Conclusion

U-CD11b and U-CD163 reflect clinical and histological disease activity of AAV renal manifestations, in particular glomerular crescentic formation. Moreover, these two biomarkers can respectively associate with the glomerular infiltrates of different leukocyte subsets in endo- and extra- capillary. U-CD163 may superior to U-CD11b for the evaluation of therapeutic efficacy in clinical settings.