Yonsei Med J.  2012 May;53(3):587-592. 10.3349/ymj.2012.53.3.587.

Urinary Hypoxia-Inducible Factor-1alpha Levels Are Associated with Histologic Chronicity Changes and Renal Function in Patients with Lupus Nephritis

• Ma C
• Wei J
• Zhan F
• Wang R
• Fu K
• Wan X
• Li Z

• KMID: 1776995
• DOI: http://doi.org/10.3349/ymj.2012.53.3.587

Abstract

PURPOSE
Tubulointerstitial hypoxia in the kidney is considered a hallmark of injury and a mediator of the progression of tubulointerstitial fibrosis. Hypoxia-inducible factor-1alpha (HIF-1alpha), a master transcription factor in cellular adaptation to hypoxia, regulates a wide variety of genes, some of which are closely associated with tissue fibrosis. The present study set out to characterize urinary HIF-1alpha expressions in patients with lupus nephritis (LN) and to explore whether urinary HIF-1alpha expressions are associated with histologic chronicity changes and renal function.
MATERIALS AND METHODS
Urinary HIF-1alpha levels were measured by enzyme-linked immunosorbent assays in 42 patients with LN and in 30 healthy controls. Activity and chronicity indexes as well as tubular HIF-1alpha expressions were analyzed for each specimen.
RESULTS
Urinary HIF-1alpha levels were higher in LN patients than in healthy controls (3.977+/-1.696 vs. 2.153+/-0.554 ng/mL, p<0.001) and were associated with histologic chronicity indexes (r=0.463, p<0.01) and eGFR (r=-0.324, p<0.05). However, urinary HIF-1alpha levels showed no correlation with histologic activity indexes, anti-dsDNA, ANA, complement 3 and 4 levels, proteinuria, systemic lupus erythematosis disease activity index, and WHO pathological classification (p>0.05).
CONCLUSION
Urinary HIF-1alpha levels were elevated in LN patients and were associated with histologic chronicity changes and renal function, indicating that HIF-1alpha might contribute to histologic chronicity in LN.

Keyword

Hypoxia-inducible factor-1alpha; lupus nephritis; histologic chronicity change; renal function

MeSH Terms

Adolescent
Adult
Enzyme-Linked Immunosorbent Assay
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit/*urine
Kidney/metabolism/pathology
Lupus Nephritis/*urine
Male
Young Adult

Figure

• 

  Fig. 1 Urinary HIF-1alpha levels in patients with lupus nephritis and in healthy controls. Urinary HIF-1alpha levels were significantly higher in patients with lupus nephritis than in healthy controls (3.977±1.696 vs. 2.153±0.554 ng/mL, p<0.001). The bars indicate group mean values (A). Urinary HIF-1alpha levels were associated with histologic chronicity indices (r=0.463, p<0.01) (B) and eGFR (r=-0.324, p<0.05) (C). HIF, hypoxia-inducible transchiption factor.

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