M-CSF, inducing CD163 macrophages, is associated with severity and prognosis of glomerulonephritis in microscopic polyangiitis

Rapid progressive glomerulonephritis (RPGN) is a severe complication of microscopic polyangiitis (MPA), leading to end-stage renal disease (ESRD). However, biomarkers for assessing the disease severity have not been elucidated in MPA-RPGN. The aim in this exploratory hypothesis-generating study was to identify serum biomarkers associated with renal disease severity and prognosis in patients with MPA. This study enrolled 73 patients with MPA. We measured 16 serum biomarker profiles, and compared them between patients with MPA with RPGN and those without RPGN. We identified biomarkers with higher levels in MPA with RPGN and evaluated their associations with progression to ESRD. Five kidney biopsy specimens were examined by haematoxylin and eosin staining and immunostaining to evaluate the biomarker expressions. Of the 73 patients, 30 patients (41.1%) had RPGN on admission. Initial serum M-CSF levels and TNF-a levels were significantly higher in patients with MPA with RPGN than those without RPGN. Among them, serum M-CSF levels significantly correlated with glomerular and renal tubular damage markers. The 5-year ESRD-progression rate was significantly higher in patients with initial serum M-CSF ≥ 416.95 pg/ml than in patients with serum M-CSF < 416.95 pg/ml (P = 0.0002). Immunohistochemical staining showed enhanced M-CSF expression in glomerular capillary endothelial cells and tubular epithelial cells in cases with severe glomerular and tubular damage. CD163-positive macrophages showed high infiltration into the periglomerular and peritubular areas in the sclerotic group. The serum M-CSF level may serve as a biomarker that reflects RPGN severity and predicts progression to ESRD in patients with MPA. M-CSF-inducing CD163 + macrophages might contribute to the pathogenesis of RPGN in MPA.