However, hypoxia-induced fibrosis may not be a vicious circle that further worsens oxygenation, but merely a way to maintain renal oxygenation by adapting oxygen consumption to the demand. Identical mechanisms might operate in animals. Animal models reporting hypoxia in CKD such as the 5/6 nephrectomy model may not have been carried out long enough to simulate the long-term adaptive changes in the kidney that might occur after several decades of chronic kidney disease or hypertension in humans. In line with this hypothesis, Priardarshy et al evaluated renal oxygenation six to eight weeks after remnant kidney creation, and found that renal oxygenation was not decreased, but rather increased in the remnant kidney. A similar observation was made in renal artery stenosis with a reduction of renal tissue oxygenation acutely but a good maintenance of tissue oxygenation in the chronically stenotic kidney. A role of renal handling of sodium in mediating oxygen consumption is supported by our observation that the medullary R2* response to furosemide differs between controls and hypertensives with a blunted response in hypertension and an even more marked reduction in CKD patients. In CKD, the markedly reduced response to furosemide can be explained by the reduced renal function leading to lower concentrations of furosemide within the kidney. However, this cannot be the explanation for hypertensive patients who had a comparable renal function as controls. Pratt et al have previously demonstrated ethnic differences in the response to furosemide ; to the best of our knowledge, differences in response to furosemide between normo-and hypertensive white subjects have not been reported previously. The blunted response to furosemide observed in hypertensive patients may be an indirect marker of the alterations in renal sodium handling in hypertension. Persons with essential hypertension have an increased proximal tubular reabsorption and a reduced distal delivery of sodium, which might blunt the effect of furosemide. Alternatively, there might be differences in mitochondrial metabolism and oxygen consumption in the thick ascending limb of Henle between hypertensive and normotensive subjects, in analogy with recently described differences between Dahl salt-sensitive rats and salt-resistant control strains. Our multivariate analysis enabled us to identify several new factors associated with renal tissue oxygenation. Thus, cortical R2* levels was positively and strongly associated with male gender. The relationship with male gender was robust and persisted in sensitivity analyses, and suggests that cortical oxygenation might be regulated differently in men and women. It may also provide some clues why renal function declines faster in men. The herein described association offers an alternative explanation in humans for to the relationship between badly controlled diabetes mellitus and adverse renal outcome.