ArticleAmerican journal of physiology. Renal physiology2017
Hypoxia-inducible factor-1α activation improves renal oxygenation and mitochondrial function in early chronic kidney disease.
Article in American journal of physiology. Renal physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Trial
- Review
- The gut-kidney axis in high-altitude hypoxia: pathophysiological mechanisms and the central role of hypoxia inducible factor.Annals of medicine · 2025Review
- Article
- The application of the triglyceride-glucose-body mass index (TyG-BMI) in predicting acute kidney injury in diabetic patients following coronary artery bypass grafting surgery.Journal of cardiothoracic surgery · 2025Article
- Mesenchymal Stem Cell-conditioned Medium Attenuated CoClCurrent pharmaceutical design · 2025Article
- Triglyceride-glucose index in the prediction of acute kidney injury in patients undergoing coronary artery bypass surgery.Frontiers in cardiovascular medicine · 2025Article
- Research progress of hypoxia-inducible factor-1α and zinc in the mechanism of diabetic kidney disease.Frontiers in pharmacology · 2025Review
- Review
- Association between triglyceride-glucose index and AKI in ICU patients based on MIMICIV database: a cross-sectional study.Renal failure · 2023Article
- HIF-1α promotes kidney organoid vascularization and applications in disease modeling.Stem cell research & therapy · 2023Article
- Renal Assessment in Acute Cardiorenal Syndrome.Biomolecules · 2023Review
- Review
- The sugar daddy: the role of the renal proximal tubule in glucose homeostasis.American journal of physiology. Cell physiology · 2022Review
- A bioinspired carbon monoxide delivery system prevents acute kidney injury and the progression to chronic kidney disease.Redox biology · 2022Article
- Renoprotective Role of Hypoxia-Inducible Factors and the Mechanism.Kidney diseases (Basel, Switzerland) · 2022Review
- Stabilization of hypoxia-inducible factor ameliorates glomerular injury sensitization after tubulointerstitial injury.Kidney international · 2021Article
- Hypoxia-mediated regulation of mitochondrial transcription factors in renal epithelial cells: implications for hypertensive renal physiology.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Renoprotective Effect of the Recombinant Anti-IL-6R Fusion Proteins by Inhibiting JAK2/STAT3 Signaling Pathway in Diabetic Nephropathy.Frontiers in pharmacology · 2021Article
- HIF-1α ameliorates tubular injury in diabetic nephropathy via HO-1-mediated control of mitochondrial dynamics.Cell proliferation · 2020Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The pathophysiology of chronic kidney disease (CKD) is driven by alterations in surviving nephrons to sustain renal function with ongoing nephron loss. Oxygen supply-demand mismatch, due to hemodynamic adaptations, with resultant hypoxia, plays an important role in the pathophysiology in early CKD. We sought to investigate the underlying mechanisms of this mismatch. We utilized the subtotal nephrectomy (STN) model of CKD to investigate the alterations in renal oxygenation linked to sodium (Na) transport and mitochondrial function in the surviving nephrons. Oxygen delivery was significantly reduced in STN kidneys because of lower renal blood flow. Fractional oxygen extraction was significantly higher in STN. Tubular Na reabsorption was significantly lower per mole of oxygen consumed in STN. We hypothesized that decreased mitochondrial bioenergetic capacity may account for this and uncovered significant mitochondrial dysfunction in the early STN kidney: higher oxidative metabolism without an attendant increase in ATP levels, elevated superoxide levels, and alterations in mitochondrial morphology. We further investigated the effect of activation of hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular hypoxia response. We observed significant improvement in renal blood flow, glomerular filtration rate, and tubular Na reabsorption per mole of oxygen consumed with HIF-1α activation. Importantly, HIF-1α activation significantly lowered mitochondrial oxygen consumption and superoxide production and increased mitochondrial volume density. In conclusion, we report significant impairment of renal oxygenation and mitochondrial function at the early stages of CKD and demonstrate the beneficial role of HIF-1α activation on renal function and metabolism.
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