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

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 β₂-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.

Determination of an Angiotensin II-regulated Proteome in Primary Human Kidney Cells by Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC)

“…HO-1 protein excretion in urine is low or undetectable in normal humans and mice, but it was increased in humans and animals with acute kidney injury (80), another setting where RAS activation may contribute to kidney injury. 5 HO-1 protein expression was also increased in tubular cells isolated from the urine of patients with tubulointerstitial disorders (81). Finally, we found a direct linear relationship between kidney HO-1 protein expression and urine HO-1 excretion, suggesting that HO-1 excreted in urine is determined by its renal production.…”

Nuclear factor kappa B in urine sediment: a useful indicator to detect acute kidney injury in Plasmodium falciparum malaria

“…Either NF-κB p65 was not excreted into the urine or the molecule was too diluted within the urine to be measurable directly. Similar finding was documented for urinary haem oxygenese-1 (uHO-1) measurement, where it was undetectable in the urine supernatant [22]. Activation of NF-κB p65 has been demonstrated in glomeruli, in tubulo-interstitial cells, in infiltrating cells of obstructed kidneys [23], as well as in renal tubular cells [14].…”

“…Activation of NF-κB p65 has been demonstrated in glomeruli, in tubulo-interstitial cells, in infiltrating cells of obstructed kidneys [23], as well as in renal tubular cells [14]. The proximal and distal tubular epithelial cells were documented as major NF-κB p65 producers [22]. Recent studies show that NF-κB p65 activation has also been detected in peripheral blood mononuclear cells (PBMCs) from complicated P. falciparum malaria patients [24].…”

Plasma and Urinary Heme Oxygenase-1 in AKI

“…This was felt to reflect the effects of hyperglycemia, a known pro-oxidant state. In a second study, Yokoyama et al, 27 reported that critically ill patients (e.g., after cardiac arrest) manifested increased plasma HO-1 levels. However, it is unclear how much concomitant renal injury was sustained in this patient population.…”