Tubular osteopontin expression in human glomerulonephritis and renal vasculitis

Abstract

Tubulointerstitial change is a common histopathologic feature of acute and chronic glomerular diseases and is more closely correlated than glomerular damage with renal function and subsequent outcome. Monocyte infiltration is presumed to be initiated by chemoattractants and has a pivotal role in tubulointerstitial changes. Osteopontin (OPN) is a candidate as such a chemoattractant and has been shown to recruit monocytes into the interstitium of animal models of renal diseases. In this study, we investigated OPN expression by immunostaining and its correlation with clinical and histopathologic parameters in patients with immunoglobulin A (IgA) nephropathy, diffuse proliferative lupus nephritis (DPLN), and myeloperoxidase-antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis (MMP). Twenty patients with IgA nephropathy, 12 patients with DPLN, and 14 patients with MMP were studied. OPN expression, which was constitutively observed on the apical membrane of distal tubules, was upregulated in the cytoplasm of proximal and distal tubular epithelium parallel to the degree of interstitial mononuclear cell infiltration in patients with IgA nephropathy, as well as those with DPLN. CD68(+) monocyte infiltration significantly correlated with the degree of OPN expression in the tubular epithelium. Conversely, there was no apparent induction of OPN in the proximal and distal tubular epithelium of patients with MMP despite remarkable monocyte infiltration. In conclusion, these data suggest that inducible expression of OPN in the tubular epithelium seems to be associated with interstitial monocyte infiltration and subsequent tubulointerstitial changes in some forms of human renal diseases.