Contrast-Enhanced Ultrasound For Assessing Renal Perfusion Impairment And Predicting Acute Kidney Injury To Chronic Kidney Disease Progression

BackgroundAcute kidney injury(AKI)is a global public health concern associated with high morbidity,mortality,and healthcare costs.Large population-based studies have demonstrated that patients who survive an episode of AKI are at considerable risk for progressing to advanced stages of chronic kidney disease(CKD).These data are sobering and demonstrate the continuity of disease from AKI to CKD to end-stage renal disease(ESRD).Although multiple clinical factors such as pre-existing conditions and increasing age play a role,the severity of AKI seems to be the most important risk factor for future CKD.Quantitative assessment of the AKI severity may help to identify patients who are at high risk of AKI-CKD progression,so that proper follow-up and secondary prevention may be implemented or studied in this population.Then the natural history of this progression might be favorably altered.AKI has profion leading to ongoing ischemic conditions and further injuound effects on the renal endothelium resulting in microvascular dysfunctry following the initial insult.Capillary rarefaction and endothelial injury are important pathophysiological processes promoting renal fibrosis and CKD.Total renal blood flow(RBF)may have little bearing on regional microvascular flow and as human biopsies show,patchy areas of injury.Therefore,understanding microvascular flow is far more important than total RBF and represents an attractive therapeutic target.Endothelial injury resulting in capillary rarefaction has been identified as a hallmark of CKD development.Prior studies using tissue samples from patients and various CKD animal models have shown that fibrosis progression is associated with a continuous rarefaction of glomerular and cortical peritubular capillaries.Several recent studies suggested that restoring the renal microvasculature may provide novel therapeutic options for patients with CKD.Assessing renal perfusion have the potential to help(i)identify alters of renal function and determine the effectiveness of therapeutic maneouvres;and(ii)determine whether there is potentially recoverable renal function.Although alterations in renal microvascular perfusion are thought to play a causative role in the pathogenesis of AKI,the diagnostic tools for assessing renal perfusion are particularly lacking.Contrast enhanced ultrasound(CEUS)is a novel imaging technique associated with low mechanical index ultrasonography and microbubble-based contrast agents.These microbubbles,when injected into the bloodstream,allow visualization of vascular structures and,with contrast-specific imaging modes,detection of blood flow at the capillary level.The present study was designed to test the hypothesis that renal perfusion measured by CEUS may serve as a noninvasive approach to determine the AKI severity and to early predict the subsequent chronic kidney damage.MethodsTo model a broad spectrum of renal diseases,address potential disease-specific differences and describe the time-dependent dynamics of vascular alterations and their association with renal fibrosis,we have used three distinct models:ischemia-reperfusion-induced progressive kidney injury(IRI),unilateral ureteral obstruction(UUO)and a model of drug-induced nephrotoxicity,namely folic acid treated mice.For this purpose,the study determined whether CEUS can show serial changes in renal perfusion and whether the imaging results can predict the progression to CKD after AKI in three mouse models and in human AKI.Conclusions1?The degree of renal injury correlates with chronic kidney damage.2?CEUS is able to determine the severity of AKI and quantify impairment of renal microvascular perfusion over time.3?Renal microvascular perfusion measured by CEUS may serve as a noninvasive approach to determine the AKI severity and to early predict the subsequent chronic kidney damage.4?These findings justify the future clinical investigations for AKI to CKD progression.