Abstract
The high renal oxygen (O(2) ) demand is associated primarily with tubular O(2) consumption (Qo(2) ) necessary for solute reabsorption. Increasing O(2) delivery relative to demand via increased blood flow results in augmented tubular electrolyte load following elevated glomerular filtration, which, in turn, increases metabolic demand. Consequently, elevated kidney metabolism results in decreased tissue oxygen tension. The metabolic efficiency for solute transport (Qo(2) /T(Na) ) varies not only between different nephron sites, but also under different conditions of fluid homeostasis and disease. Contributing mechanisms include the presence of different Na(+) transporters, different levels of oxidative stress and segmental tubular dysfunction. Sustained hyperglycaemia results in increased kidney Qo(2) , partly due to mitochondrial dysfunction and reduced electrolyte transport efficiency. This results in intrarenal tissue hypoxia because the increased Qo(2) is not matched by a similar increase in O(2) delivery. Hypertension leads to renal hypoxia, mediated by increased angiotensin receptor tonus and oxidative stress. Reduced uptake in the proximal tubule increases load to the thick ascending limb. There, the increased load is reabsorbed, but at greater O(2) cost. The combination of hypertension, angiotensin II and oxidative stress initiates events leading to renal damage and reduced function. Tissue hypoxia is now recognized as a unifying pathway to chronic kidney disease. We have gained good knowledge about major changes in O(2) metabolism occurring in diabetic and hypertensive kidneys. However, further efforts are needed to elucidate how these alterations can be prevented or reversed before translation into clinical practice.