Hypoxia-inducible factor-1α activation improves renal oxygenation and mitochondrial function in early chronic kidney disease.

摘要: 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 hemodynamic adaptations, resultant hypoxia, plays an important role the early CKD. We sought investigate underlying mechanisms this mismatch. utilized subtotal nephrectomy (STN) model CKD oxygenation linked sodium (Na) transport and mitochondrial nephrons. delivery was significantly reduced STN kidneys because lower blood flow. Fractional oxygen extraction higher STN. Tubular Na reabsorption per mole consumed hypothesized that decreased bioenergetic capacity may account for uncovered significant dysfunction kidney: oxidative metabolism without attendant increase ATP levels, elevated superoxide morphology. further investigated effect activation hypoxia-inducible factor-1α (HIF-1α), a master regulator cellular hypoxia response. observed improvement flow, glomerular filtration rate, tubular HIF-1α activation. Importantly, lowered consumption production increased volume density. In conclusion, we report impairment at stages demonstrate beneficial on metabolism.