Urinary-Hypoxia Inducible Factor-1 alpha and its Association With Histological Chronicity Changes In Lupus Nephritis Patients

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease which can cause multisystem affection.

Kidney involvement in patients with SLE is a common and serious complication that is often associated with a poor long-term prognosis.

Current laboratory markers for Lupus Nephritis (LN) such as proteinuria, urine, protein-to-creatinine ratio, creatinine clearance, anti-dsDNA, and complement (C) levels are unsatisfactory. They lack sensitivity and specificity for differentiating renal damage in LN. Significant kidney damage can occur before renal function is impaired.

Thus, novel biomarkers that are able to discriminate lupus renal chornicity and its severity, predict renal damage, and monitor treatment response and disease progress are clearly necessary.

The family of hypoxia-inducible factors (HIFs) are central regulators of hypoxic responses. HIFs regulate several target genes that have important functions in renal physiologic and pathophysiologic processes, including energy metabolism, vasomotor regulation, angiogenic growth, matrix metabolism, and apoptosis/cell survival. HIF-1 is a heterodimer composed of a constitutively expressed HIF-1β subunit and an O2-regulated HIF-1alpha subunit. HIF-1alpha plays a central role in the hypoxic response of tubular epithelial cells. Indeed, hypoxia-inducible gene expression in primary renal proximal tubular epithelial cells is almost completely blocked by inactivation of HIF-1alpha, suggesting that their response to hypoxia is largely dependent on HIF-1alpha. In addition, genetic ablation of HIF-1alpha inhibited the development of tubulointerstitial fibrosis in vivo.