SUN-380 CLINICAL IMPACTS OF URINARY CD11B AND CD163 ON PATIENT OUTCOMES IN ANCA-ASSOCIATED GLOMERULONEPHRITIS

Abstract

The leukocyte-derived molecules, CD11b (α subunit of leukocyte integrin Mac-1) and scavenger receptor CD163, undergo ectodomain cleavage upon inflammation-related cell activation; therefore, the presence of these molecules in urine may reflect the renal inflammation with glomerular crescents containing robust extra-capillary leukocytes in anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN). This study was undertaken to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. We examined ANCA-GN urine samples by enzyme-linked immunosorbent assay in our institutional cohort (88 patients at diagnosis) and in a nation-wide ANCA vasculitis (AAV) cohort (138 patients at diagnosis; 56 patients after 6 months of treatment) and analyzed the associations of the results with renal histology related to ANCA-GN, and with remission status and patient outcome evaluated by the renal Vasculitis Damage Index (VDI) score at 6 months after remission induction therapy. Both U-CD11b and U-CD163 at diagnosis were significantly elevated in patients with ANCA-GN compared to those in with nephrosclerosis (n=20) and IgG4-related disease (n=12). Those in tubulointerstitial nephritis (n=15) demonstrated a mild increase of U-CD11b, but not of U-CD163, at levels statistically comparable to that of AAV. Histological analysis in tubulointerstitial area demonstrated moderate correlation of U-CD11b with interstitial CD11b+ infiltrates. When focusing on glomerular injury, U-CD11b and U-CD163 levels were increased particularly in patients with ANCA-GN in the crescentic category according to the European Vasculitis Study Group classification. Detailed histological analyses evidenced the significant associations of U-CD11b and U-CD163 levels with cellular crescent formation and accumulation of leukocytes expressing the surface markers in glomerular crescents. Although the levels of U-CD163, but not of U-CD11b, in identical patients at diagnosis were significantly reduced after the 6-month follow-up period, patients with unachieved remission at 6 months showed significant elevation of U-CD163 at diagnosis, but not at 6 months. In contrast, baseline U-CD11b levels did not affect the remission status after 6 months of treatment, but the levels at 6 months tended to be decreased in patients with unachieved remission. Analyses of U-CD11b and U-CD163 levels according to the renal VDI score revealed significant elevation of U-CD11b at 6 months and U-CD163 at diagnosis in ANCA-GN patients with a renal VDI score ≥ 2 compared to those with score of 0 at 6 months. Receiver operating characteristic curves for U-CD11b and U-CD163 at diagnosis demonstrated the superiority of U-CD163 to U-CD11b as a biomarker to predict the remission status (AUC; U-CD11b 0.517, U-CD163 0.723) and renal VDI score ≥ 2 (AUC; U-CD11b 0.647, U-CD163 0.785) at 6 months after remission induction therapy. U-CD11b and U-CD163 have different clinical values: U-CD11b reflects the ANCA-GN inflammatory status in the glomerulus and tubulointerstitium, and is associated with persistent renal damages, whereas U-CD163 specifically reflects glomerular inflammation and is associated with susceptibility to immunosuppressive treatment.