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

Abstract

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.

Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy

“…Renal dysfunction correlates with the extent of ATN, identified in the more severe protocols, but less so with the more moderate models that cause limited tubular damage, as probably happens in general in the human scenario of "ATN," in which the degree of glomerular filtration dysfunction does not correlate with the extent of focal tubular injury, underscoring a potential role for ensuing altered glomerular hemodynamics as the basis for the decline in kidney function (46). In such circumstances, novel technologies such as sodium MRI for the early detection of evolving altered medullary countercurrent mechanism (49) or the use of potentially noninvasive real-time molecular imaging of necrotic/apoptotic injury (50) might help to differentiate between evolving true ATN and renal dysfunction reflecting altered glomerular hemodynamics.…”

Acute Tubular Necrosis Is a Syndrome of Physiologic and Pathologic Dissociation

“…28 Interestingly, renal sodium MRI can detect early loss of tubular function (diminished sodium concentration gradient) in this model when there is still very limited tubular injury. 29 The recent introduction of extended sepsis models more analogous to the human situation (with the use of fluid resuscitation, antibiotics, and inotropes), and the finding of primary toll-like receptors for Gram-negative toxins, such as TLR4 and their effector proteins, such as MyD88, have also led to a deeper understanding of acute renal failure in sepsis. 30 The minimal morphologic lesions present underscore their clinical relevance.…”

Response of the Renal Inner Medulla to Hypoxia: Possible Defense Mechanisms

“…The deep region of the renal outer medulla should be vulnerable to hypoxia owing to its precarious blood supply [1] and high rate of consumption of O 2 due to active reabsorption of Na + in the medullary thick ascending limb of Henle’s loop (mTAL) [2,3]. One of the major consequences of hypoxia in this region [4] may be changes in the functions of juxtamedullary nephrons, with an expected defect in their reabsorption of Na + , Cl – and water [5,6].…”