Urinary Heme Oxygenase-1 as a Sensitive Indicator of Tubulointerstitial Inflammatory Damage in Various Renal Diseases

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.