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

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.