Urinary heme oxygenase-1 as a sensitive indicator of tubulointerstitial inflammatory damage in various renal diseases

Am J Nephrol. 2011;33(5):414-20. doi: 10.1159/000327020. Epub 2011 Apr 18.

Abstract

Background/aims: In oxidative stress, heme oxygenase-1 (HO-1) plays a pivotal role in maintaining renal function and protecting renal structure, especially in renal tubular epithelial cells. We examined urinary HO-1 (uHO-1) levels to assess whether uHO-1 acts as a sensitive biomarker for detecting tubulointerstitial inflammatory damage in renal diseases.

Methods: Immunohistochemical analyses and enzyme-linked immunosorbent assays for uHO-1 were performed using 61 urine samples (supernatants and sediment lysates) from healthy children and renal disease patients.

Results: Proximal and distal epithelial cells showed higher uHO-1 levels than squamous and urothelial cells. Inflammatory renal disease patients had higher uHO-1 levels than noninflammatory renal disease patients and controls. In IgA nephropathy, patients with interstitial cellular infiltration showed higher uHO-1 levels than those without it. Among patients with increased urinary β(2)-microglobulin or N-acetyl-β-D-glucosaminidase levels, uHO-1 levels increased only in those with renal disease and tubulointerstitial inflammatory damage. uHO-1 levels positively correlated with urinary interleukin-6 in inflammatory renal disease patients.

Conclusions: These results indicate that uHO-1 is a potentially useful, novel, and noninvasive biomarker for evaluating the degree of tubulointerstitial inflammatory damage in renal disease.

MeSH terms

  • Acetylglucosaminidase / urine
  • Adolescent
  • Biomarkers / metabolism
  • Biomarkers / urine
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Glomerulonephritis, IGA / urine
  • Heme Oxygenase-1 / metabolism*
  • Heme Oxygenase-1 / urine*
  • Humans
  • Immunohistochemistry / methods
  • Inflammation
  • Interleukin-6 / urine
  • Kidney Diseases / diagnosis*
  • Kidney Diseases / urine*
  • Kidney Tubules / pathology
  • Male
  • beta 2-Microglobulin / urine

Substances

  • Biomarkers
  • Interleukin-6
  • beta 2-Microglobulin
  • Heme Oxygenase-1
  • Acetylglucosaminidase