Background: Apoptosis inhibitor of macrophage (AIM) expressed on macrophages prolongs inflammation by protecting macrophages from apoptosis. Most circulating AIM co-exists with immunoglobulin M (IgM). AIM's pathophysiological role in relation to IgM remains unclear. Here we evaluated the glomerular expression/deposition of AIM and IgM in the kidney using immunohistochemistry and its associations with clinical manifestations in 43 patients with biopsy-confirmed kidney diseases.
Methods: Kidney biopsy tissue from all patients was immunostained for AIM and IgM. Staining patterns and percent stained areas within the glomeruli were determined. Cells expressing AIM were identified by co-staining with macrophage and endothelial cell surface markers. Correlations between staining results and clinical parameters were evaluated using univariate and multivariate analyses.
Results: AIM was deposited in various areas, such as mesangial and capillary area. A part of AIM expression was localized to CD68-positive macrophages in the glomerulus. Amount of glomerular expression was positively correlated with urinary protein in patients with severe proteinuria (urinary protein ≥0.5 g/day) and kidney dysfunction [estimated glomerular filtration ratio (eGFR) <60 ml/min/1.73 m2]. Urinary protein was higher in patients exhibiting overlapping glomerular expression of AIM and IgM. Annual eGFR decline rate negatively correlated with AIM-positive area. AIM-positive area and initial serum creatinine were independently associated with decreased kidney function.
Conclusion: AIM expression in the kidney was associated with urinary protein and decline in kidney function. Co-expression with IgM appeared to exacerbate AIM's deleterious effects on kidney function. Combined glomerular AIM and IgM expression is a candidate prognostic index for kidney disease.
Keywords: Apoptosis inhibitor of macrophage (AIM); IgM; Kidney disease.