Apoptosis inhibitor of macrophage as a biomarker for disease activity in Japanese children with IgA nephropathy and Henoch-Schönlein purpura nephritis

Pediatr Res. 2021 Feb;89(3):667-672. doi: 10.1038/s41390-020-0951-1. Epub 2020 May 14.

Abstract

Background: To evaluate the apoptosis inhibitor of macrophage (AIM) deposition patterns on the kidneys of children with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) and to investigate the clinical usefulness of serum and/or urinary AIM levels as biomarkers for the disease activity.

Methods: Immunohistochemical study was performed in the kidneys of 37 patients with IgAN and 10 patients with HSPN. Serum and urinary AIM levels in the patients and 20 healthy controls (HCs) were quantified by enzyme-linked immunosorbent assay. The results were compared with clinical features.

Results: In patients with IgAN and HSPN, AIM expression was observed in various areas, including the glomerular mesangial and capillary areas, the proximal and distal tubular epithelial cells, and on infiltrating macrophages in the glomeruli and interstitial areas. Serum and urinary AIM levels were significantly elevated in these patients compared with the HCs. Urinary AIM levels were positively correlated with the histological severity and degree of proteinuria and hematuria as well as urinary β2 microglobulin and urinary N-acetyl-β-D-glucosaminidase levels.

Conclusions: AIM plays an important role in the pathogenesis of IgAN and HSPN. Urinary AIM levels can potentially reflect active renal inflammation in these diseases and may represent a useful biomarker for disease activity.

Impact: Urinary AIM levels may represent a useful biomarker for disease activity of IgAN and HSPN. AIM expression was observed in the glomeruli, tubular epithelial cells, and infiltrating macrophages in glomeruli and interstitial area. U-AIM/Cr were significantly correlated not only with proteinuria, hematuria, and u-β2MG and u-NAG levels but also with the activity index of histological findings in kidney biopsy specimens. Our results can emphasize the important role of AIM in the pathogenesis of IgAN and HSPN.

MeSH terms

  • Adolescent
  • Apoptosis
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Biomarkers / metabolism*
  • Biopsy
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Glomerulonephritis, IGA / genetics*
  • Glomerulonephritis, IGA / metabolism
  • Humans
  • IgA Vasculitis / genetics*
  • IgA Vasculitis / metabolism
  • Immunohistochemistry
  • Inflammation
  • Japan
  • Kidney / pathology
  • Kidney Glomerulus / metabolism
  • Leukocyte Count
  • Macrophages / metabolism
  • Male
  • Receptors, Scavenger / biosynthesis*

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers
  • CD5L protein, human
  • Receptors, Scavenger