Hypoxia Inducible Factor 1: A Urinary Biomarker of Kidney Disease

Abstract

Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF‐1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF‐1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF‐1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF‐1a mRNA is of kidney origin, we examined colocalization of HIF‐1a mRNA with two kidney specific markers in urine cells. We found that HIF‐1a mRNA is readily quantifiable in urine pellets and its expression was significantly higher in CKD patients compared with healthy adults. We also showed that the urinary HIF‐1a mRNA comes primarily from cells of renal origin. Our data suggest that urinary HIF‐1a mRNA is a potential biomarker in CKD and can be noninvasively assessed in patients.

Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of Intravenous Iron Therapy for OIT-Nonresponders

“…HIF prolyl hydroxylase (HIF-PHD) inhibitors, which stabilize HIF, can increase Hb by inhibiting hepcidin-25 regardless of iron status in HD patients [ 54 ]. In fact, urine HIF-α mRNA was increased in CKD patients than controls [ 55 ]. Further studies are needed to determine the predictive values of these factors for the response to iron therapy in HD patients.…”

Regulation of Vascular Calcification by Reactive Oxygen Species

“…Medial arterial calcification is common in CKD and is associated with poor clinical outcomes. Recent studies revealed that renal tissue hypoxia is present in CKD, and hypoxia is the driving force of the pathogenesis of CKD, triggering renal fibrosis and contributing to the development of anemia, inflammation, and aberrant angiogenesis [ 128 , 129 , 130 ]. CKD-associated hypoxia is not strictly localized to the renal tissue, but is also present in the vasculature [ 61 ].…”

Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure Control

“…The HIF pathway has been implicated with renal development, normal kidney function, and disease (Haase, 2006 ). Recently HIF-1α mRNA has been suggested to be a potential biomarker in chronic kidney disease, and comes primarily from cells of renal origin (Movafagh et al, 2017 ). Interestingly, the carotid body glomus cells constitutively overexpress HIFs and certain HIF transcriptional targets that are normally part of the counteractive mechanism against the negative impacts of sustained hypoxia (Zhou et al, 2016 ).…”