Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy

Abstract

Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after acute kidney injury, designed to interdict renal tubular damage. Magn Reson Med 79:3144-3153, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Physiological system analysis of the kidney by high‐temporal‐resolution monitoring of an oxygenation step response

“…To this end, it is warranted to extend the current study to other models of AKI and chronic kidney disease, which generally involve declined renal function and/or renal tissue hypoperfusion induced by microcirculatory dysfunction. 6,54,[59][60][61] Last but not least, it is a recognized limitation of our work that a comprehensive physiological explanation of our results warrants further research, including the application of test stimuli that go beyond the breathing gas challenges used in this study.…”

“…Three days prior to MRI examinations, four rats underwent IR-I as an AKI model using 45-minute bilateral renal artery clamping followed by reperfusion. 54 Animals were intubated and ventilated throughout the experiment using gas mixtures with different fractions of inspired oxygen (FiO 2 ). For this purpose, tanks of hyperoxic (100% O 2 ) and hypoxic (90% N 2 + 10% O 2 ) gas were coupled to an isoflurane vaporizer (VetEquip V-1; VetEquip, Livermore, CA), which was then connected to a ventilator (Ventilators TOPO; Kent Scientific, Torrington, CT).…”

The sympathetic nervous system in acute kidney injury

“…45 Studies on regional renal perfusion in mice and rats revealed that blood flow to the outer and inner renal medulla is disproportionately compromised during acute reperfusion of ischaemic kidneys, 53,54 which likely contributes to the specific localization of morphological renal alterations in response to IR. Data from a study comparing renal damage in animals with central sympathetic inhibition prior to renal artery clamping vs sympathetic inhibition after clamp release support this notion (see below).…”

“…10 During acute renal ischaemia, the activity of renal sensory nerves was found to be elevated. 25,26,36 Visceral spinal afferent neurons including nociceptors can be activated by substances released from damaged tissues (so called damage or danger-associated molecular patterns, DAMPs); 8 Unilateral after UNX 1 44 Unilateral without UNX 1 31 Rat Bilateral 2 45,54 Unilateral after UNX 13 20,[23][24][25]27,28,[33][34][35]46,50,69,73 Unilateral without UNX 3 26,39,52 Rabbit Unilateral after UNX 2 42,43 Dog Unilateral after UNX 1 49 Abbreviation: UNX, uninephrectomy.…”

“…Data from a study comparing renal damage in animals with central sympathetic inhibition prior to renal artery clamping vs sympathetic inhibition after clamp release support this notion (see below). 45 Studies on regional renal perfusion in mice and rats revealed that blood flow to the outer and inner renal medulla is disproportionately compromised during acute reperfusion of ischaemic kidneys, 53,54 which likely contributes to the specific localization of morphological renal alterations in response to IR. Future examinations of renal regional perfusion in combination with renal denervation techniques or administration of sympatholytic agents in IR models may clarify the relationship between renal sympathetic activation, this particular reperfusion pattern and the development of renal medullary damage.…”