Association of apoptosis inhibitor of macrophage (AIM) expression with urinary protein and kidney dysfunction

Clin Exp Nephrol. 2017 Feb;21(1):35-42. doi: 10.1007/s10157-016-1240-5. Epub 2016 Feb 5.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins
  • Biopsy
  • Endothelial Cells / chemistry
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Immunoglobulin M / analysis
  • Immunohistochemistry
  • Kidney Diseases / diagnosis
  • Kidney Diseases / metabolism*
  • Kidney Diseases / physiopathology
  • Kidney Glomerulus / chemistry*
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiopathology
  • Macrophages / chemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proteinuria / diagnosis
  • Proteinuria / metabolism*
  • Proteinuria / physiopathology
  • Receptors, Scavenger / analysis*
  • Retrospective Studies
  • Young Adult


  • Apoptosis Regulatory Proteins
  • CD5L protein, human
  • Immunoglobulin M
  • Receptors, Scavenger