Detection of evolving acute tubular necrosis with renal 23Na MRI: studies in rats.

The clinical detection of evolving acute tubular necrosis (ATN) and differentiating it from other causes of renal failure are currently limited. The maintenance of the corticomedullary sodium gradient, an indicator of normal kidney function, is presumably lost early in the course of ATN. Herein, sodium magnetic resonance imaging (23Na MRI) was applied to study the early alteration in renal sodium distribution in rat kidneys 6 h after the induction of ATN. Three-dimensional gradient echo sodium images were recorded at 4.7 T with high spatial resolution. ATN was produced by the administration of radiologic contrast medium, combined with inhibition of nitric oxide and prostaglandin synthesis. The sodium images revealed that the sham-controlled kidney exhibited a linear increase in sodium concentration along the corticomedullary axis of 30+/-2 mmol/l/mm, resulting in an inner medulla to cortex sodium ratio of 4.3+/-0.3 (n=5). In the ATN kidney, however, the cortico-outer medullary sodium gradient was reduced by 21% (P<0.01, n=7) and the inner medulla to cortex sodium ratio was decreased by 40% (P<0.001, n=7). Small, though significant, increments in plasma creatinine at this time inversely correlated with the decline in the corticomedullary sodium gradient. Histological findings demonstrated outer medullary ATN involving 4% of medullary thick ascending limbs. Hence, 23Na MRI non-invasively quantified changes in the corticomedullary sodium gradient in the ATN kidney when morphologic tubular injury was still focal and very limited. MRI detection of corticomedullary sodium gradient abnormalities may serve to identify evolving ATN at its early phases.

Kinetics of cyclocreatine and Na(+) cotransport in human breast cancer cells: mechanism of activity.

The growth-inhibitory effect of cyclocreatine (CCr) and the kinetics of CCr and Na(+) cotransport were investigated in MCF7 human breast cancer cells and its adriamycin-resistant subline with use of (31)P- and (23)Na-NMR spectroscopy. The growth-inhibitory effect in the resistant line occurred at a lower CCr concentration and was more pronounced than in the wild-type line. This correlated with an approximately 10-fold higher affinity of CCr to the transporter in the resistant line. The passive diffusion coefficient of CCr was also higher in the resistant line by three- to fourfold. The transport of CCr was accompanied by a rapid increase in intracellular Na(+). This increase was found to depend on the rate of CCr transport and varied differently with CCr concentration in the two cell lines. It is proposed that the cotransport of CCr and Na(+) followed by increased Na(+) concentration, together with the accumulation of the highly charged phosphocyclocreatine, are responsible for cell swelling and death.