Restricted accessResearch articleFirst published online 2025-6
In situ assessment of renal cortical microcirculation in septic acute kidney injury rats using contrast-enhanced ultrasound and sidestream dark-field imaging
To evaluate in situ assessment of renal cortical microcirculation (RCM) in S-AKI rats using CEUS and SDF imaging.
Methods:
CLP was performed to induce S-AKI in Sprague-Dawley rats; Sham rats served as control. CEUS and SDF imaging were sequentially applied at postoperative 24 h and 48 h to investigate the RCM.
Results:
At postoperative 24 h and 48 h, CLP rats exhibited hemodynamic deterioration and AKI. Renal injury score and positive staining for pimonidazole were significantly increased (p < 0.05). In CLP rats, parameters of RCM, including peak enhancement (PE), rise time (RT), PE/RT, time to peak (TTP), total small vessel density (TVD), perfused small vessel density (PVD), microvascular flow index (MFI), and proportion of perfused vessels (PPV) were significantly deteriorated compared to Sham rats (p < 0.05). In CLP rats, Lac was significantly negatively correlated with PE, PE/RT, TVD, PVD, PPV and MFI, and significantly positively correlated with RT and TTP. TVD, PVD, PPV and MFI were significantly positively correlated with PE and PE/RT and negatively correlated with RT and TTP.
Conclusion:
The RCM of S-AKI rats exhibited decreased blood perfusion and heterogeneity in early sepsis. CEUS and SDF imaging are effective methods for detecting the RCM.
ZarbockANadimMKPickkersP, et al.Sepsis-associated acute kidney injury: consensus report of the 28th acute disease quality initiative workgroup, nature reviews. Nephrology2023; 19: 401–417.
3.
MaSEvansRGIguchiN, et al.Sepsis-induced acute kidney injury: a disease of the microcirculation. Microcirculation2019; 26: e12483.
4.
FaniFRegolistiGDelsanteM, et al.Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury. J Nephrol2018; 31: 351–359.
5.
JoffreJHellmanJInceC,et al.Endothelial responses in sepsis. Am J Respir Crit Care Med2020; 202: 361–370.
6.
InceC. The microcirculation is the motor of sepsis. Crit Care2005; 9: S13–S19.
7.
VincentJLGrimaldiD. Novel interventions: what's new and the future. Crit Care Clin2018; 34: 161–173.
8.
SelbyNMDuranteauJ. New imaging techniques in AKI. Curr Opin Crit Care2020; 26: 543–548.
9.
DamianiECarsettiACasarottaE, et al.Microcirculation-guided resuscitation in sepsis: the next frontier?Front Med (Lausanne)2023; 10: 1212321.
10.
SeniorRBecherHMonaghanM, et al.Contrast echocardiography: evidence-based recommendations by European Association of Echocardiography. Eur J Echocardiography: J Working Group Echocardiography Eur Soc Cardiol2009; 10: 194–212.
11.
WangSZhaoPZhangY, et al.The therapeutic effects of curcumin in early septic acute kidney injury: an experimental study. Drug Des Devel Ther2021; 15: 4243–4255.
12.
LimaAvan RooijTErginB, et al.Dynamic contrast-enhanced ultrasound identifies microcirculatory alterations in sepsis-induced acute kidney injury. Crit Care Med2018; 46: 1284–1292.
13.
ShinJHwangJHParkSB,et al.Prediction of renal recovery following sepsis-associated acute kidney injury requiring renal replacement therapy using contrast-enhanced ultrasonography. Kidney Res Clin Pract2023; 42: 473–486.
14.
WatchornJHuangDBramhamK,et al.Decreased renal cortical perfusion, independent of changes in renal blood flow and sublingual microcirculatory impairment, is associated with the severity of acute kidney injury in patients with septic shock. Crit Care2022; 26: 261.
15.
HarroisAGrillotNFigueiredoS,et al.Acute kidney injury is associated with a decrease in cortical renal perfusion during septic shock. Crit Care2018; 22: 161.
16.
RenLZhaoYXiaoJ, et al.Contrast-enhanced ultrasound in evaluating the severity of acute kidney injury: an animal experimental study. Clin Hemorheol Microcirc2023; 85: 447–458.
17.
ChenRLiuDZhaoH,et al.Renal medullary perfusion differs from that in renal cortex in patients with sepsis associated acute kidney injury and correlates with renal function prognosis: a prospective cohort study. Clin Hemorheol Microcirc2024; 88: 181–198.
18.
GoedhartPTKhalilzadaMBezemerR, et al.Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation. Opt Express2007; 15: 15101–15114.
19.
den UilCABezemerRMirandaDR, et al.Intra-operative assessment of human pulmonary alveoli in vivo using Sidestream Dark Field imaging: a feasibility study. Med Sci Monit: Int Med J Exp Clin Res2009; 15: Mt137–Mt141.
20.
de BruinAFTavyAvan der SlootK, et al.Use of an image acquisition stabilizer improves sidestream dark field imaging of the serosa during open gastrointestinal surgery. J Vasc Res2016; 53: 121–127.
21.
InceCBoermaECCecconiM, et al.Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine. Intensive Care Med2018; 44: 281–299.
22.
RittirschDHuber-LangMSFlierlMA,et al.Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc2009; 4: 31–36.
23.
AstapenkoDJorOLehmannC,et al.In situ assessment of the renal microcirculation in mechanically ventilated rats using sidestream dark-field imaging. J Microsc2015; 257: 161–165.
24.
De BackerDHollenbergSBoermaC, et al.How to evaluate the microcirculation: report of a round table conference. Critical Care (London, England)2007; 11: R101–R101.
25.
VenkatachalamMABernardDBDonohoeJF,et al.Ischemic damage and repair in the rat proximal tubule: differences among the S1, S2, and S3 segments. Kidney Int1978; 14: 31–49.
De BackerDDonadelloKTacconeFS, et al.Microcirculatory alterations: potential mechanisms and implications for therapy. Ann Intensive Care2011; 1: 27.
28.
GuerciPErginBInceC. The macro- and microcirculation of the kidney. Best Pract Res Clin Anaesthesiol2017; 31: 315–329.
29.
SchneiderAGGoodwinMDSchellemanA, et al.Contrast-enhanced ultrasound to evaluate changes in renal cortical perfusion around cardiac surgery: a pilot study. Crit Care2013; 17: R138.
30.
SchneiderAGGoodwinMDSchellemanA, et al.Contrast-enhanced ultrasonography to evaluate changes in renal cortical microcirculation induced by noradrenaline: a pilot study. Crit Care2014; 18: 653.
31.
LangenbergCGobeGHoodS, et al.Renal histopathology during experimental septic acute kidney injury and recovery. Crit Care Med2014; 42: e58–e67.
32.
MaidenMJOttoSBrealeyJK, et al.Structure and function of the kidney in septic shock. A prospective controlled experimental study. Am J Respir Crit Care Med2016; 194: 692–700.
33.
WautersJClausPBrosensN, et al.Pathophysiology of renal hemodynamics and renal cortical microcirculation in a porcine model of elevated intra-abdominal pressure. J Trauma2009; 66: 713–719.
34.
SuiFZhengYLiWX,et al.Renal circulation and microcirculation during intra-abdominal hypertension in a porcine model. Eur Rev Med Pharmacol Sci2016; 20: 452–461.
35.
HuaTWuXWangW, et al.Micro- and macrocirculatory changes during sepsis and septic shock in a rat model. Shock2018; 49: 591–595.
36.
FerraraGKanoore EdulVSCaminos EguillorJF, et al.Effects of fluid and norepinephrine resuscitation in a sheep model of endotoxin shock and acute kidney injury. J Appl Physiol (Bethesda, Md.: 1985)2019; 127: 788–797.
37.
DuranteauJBackerDDDonadelloK, et al.The future of intensive care: the study of the microcirculation will help to guide our therapies. Crit Care2023; 27: 190.
38.
MasseyMJShapiroNI. A guide to human in vivo microcirculatory flow image analysis. Crit Care2016; 20: 35.
39.
PeerapornratanaSManrique-CaballeroCLGomezH,et al.Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int2019; 96: 1083–1099.
40.
VermaSKMolitorisBA. Renal endothelial injury and microvascular dysfunction in acute kidney injury. Semin Nephrol2015; 35: 96–107.
41.
PiagnerelliMBoudjeltiaKZVanhaeverbeekM,et al.Red blood cell rheology in sepsis. Intensive Care Med2003; 29: 1052–1061.
42.
BaskurtOKTemizAMeiselmanHJ. Red blood cell aggregation in experimental sepsis. J Lab Clin Med1997; 130: 183–190.
43.
NemethNBerhesMKissF, et al.Early hemorheological changes in a porcine model of intravenously given E. coli induced fulminant sepsis. Clin Hemorheol Microcirc2015; 61: 479–496.
