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

James Watchorn, Dean Huang, Kate Bramham, Sam Hutchings, James Watchorn, Dean Huang, Kate Bramham, Sam Hutchings

Abstract

Background: Reduced renal perfusion has been implicated in the development of septic AKI. However, the relative contributions of macro- and microcirculatory blood flow and the extent to which impaired perfusion is an intrinsic renal phenomenon or part of a wider systemic shock state remains unclear.

Methods: Single-centre prospective longitudinal observational study was carried out. Assessments were made at Day 0, 1, 2 and 4 after ICU admission of renal cortical perfusion in 50 patients with septic shock and ten healthy volunteers using contrast-enhanced ultrasound (CEUS). Contemporaneous measurements were made using transthoracic echocardiography of cardiac output. Renal artery blood flow was calculated using velocity time integral and vessel diameter. Assessment of the sublingual microcirculation was made using handheld video microscopy. Patients were classified based on the degree of AKI: severe = KDIGO 3 v non-severe = KDIGO 0-2.

Results: At study enrolment, patients with severe AKI (37/50) had prolonged CEUS mean transit time (mTT) (10.2 vs. 5.5 s, p < 0.05), and reduced wash-in rate (WiR) (409 vs. 1203 au, p < 0.05) and perfusion index (PI) (485 vs. 1758 au, p < 0.05); differences persisted throughout the entire study. Conversely, there were no differences in either cardiac index, renal blood flow or renal resistive index. Sublingual microcirculatory variables were not significantly different between groups at study enrolment or at any subsequent time point. Although lactate was higher in the severe AKI group at study enrolment, these differences did not persist, and there were no differences in either ScvO2 or ScvCO2-SaCO2 between groups. Patients with severe AKI received higher doses of noradrenaline (0.34 vs. 0.21mcg/kg/min, p < 0.05). Linear regression analysis showed no correlation between mTT and cardiac index (R-0.18) or microcirculatory flow index (R-0.16).

Conclusion: Renal cortical hypoperfusion is a persistent feature in critically ill septic patients who develop AKI and does not appear to be caused by reductions in macrovascular renal blood flow or cardiac output. Cortical hypoperfusion appears not be associated with changes in the sublingual microcirculation, raising the possibility of a specific renal pathogenesis that may be amenable to therapeutic intervention. Trial Registration Clinical Trials.gov NCT03713307 , 19 Oct 2018.

Keywords: Acute kidney injury; Contrast-enhanced ultrasound; Echocardiography; Microcirculation; Renal blood flow; Septic shock; Sublingual video microscopy.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Schematic diagram of typical destruction-replenishment kinetics following the administration of ultrasound contrast
Fig. 2
Fig. 2
Renal cortical perfusion assessed by CEUS variables, presented over time and between severe AKI, non-severe AKI and control groups

References

    1. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units&colon; results of the SOAP study&ast. Crit Care Med. 2006;34(2):344–353. doi: 10.1097/01.CCM.0000194725.48928.3A.
    1. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically Ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813–818. doi: 10.1001/jama.294.7.813.
    1. Post EH, Kellum JA, Bellomo R, Vincent JL. Renal perfusion in sepsis: from macro- to microcirculation. Kidney Int. 2017;91(1):45–60. doi: 10.1016/j.kint.2016.07.032.
    1. Benes J, Chvojka J, Sykora R, Radej J, Krouzecky A, Novak I, et al. Searching for mechanisms that matter in early septic acute kidney injury: an experimental study. Crit Care. 2011;15(5):R256. doi: 10.1186/cc10517.
    1. Gómez H, Kellum JA, Ronco C. Metabolic reprogramming and tolerance during sepsis-induced AKI. Nat Rev Nephrol. 2017;13(3):143–151. doi: 10.1038/nrneph.2016.186.
    1. Lima A, van Rooij T, Ergin B, Sorelli M, Ince Y, Specht PAC, et al. Dynamic contrast-enhanced ultrasound identifies microcirculatory alterations in sepsis-induced acute kidney injury. Crit Care Med. 2018;46(8):1284–1292. doi: 10.1097/CCM.0000000000003209.
    1. Harrois A, Grillot N, Figueiredo S, Duranteau J. Acute kidney injury is associated with a decrease in cortical renal perfusion during septic shock. Crit Care. 2018;22(1):161. doi: 10.1186/s13054-018-2067-0.
    1. Watchorn J, Huang DY, Joslin J, Bramham K, Hutchings SD. Critically ILL COVID-19 patients with acute kidney injury have reduced renal blood flow and perfusion despite preserved cardiac function; a case-control study using contrast enhanced ultrasound. Shock. 2020;55:479–487. doi: 10.1097/SHK.0000000000001659.
    1. Wang XY, Pang YP, Jiang T, Wang S, Li JT, Shi BM, et al. Value of early diagnosis of sepsis complicated with acute kidney injury by renal contrast-enhanced ultrasound. World J Clin Cases. 2019;7(23):3934–3944. doi: 10.12998/wjcc.v7.i23.3934.
    1. Muskula PR, Main ML. Safety with echocardiographic contrast agents. Circul Cardiovasc Imag. 2018;10(4):e005459. doi: 10.1161/CIRCIMAGING.116.005459.
    1. Watchorn J, Huang D, Hopkins P, Bramham K, Hutchings S. Prospective longitudinal observational study of the macro and micro haemodynamic responses to septic shock in the renal and systemic circulations: a protocol for the MICROSHOCK – RENAL study. BMJ Open. 2019;9(8):e028364. doi: 10.1136/bmjopen-2018-028364.
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group: KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2:1–138.
    1. Mulier JLGH, Rozemeijer S, Röttgering JG, de Man AMES, Elbers PWG, Tuinman PR, et al. Renal resistive index as an early predictor and discriminator of acute kidney injury in critically ill patients; a prospective observational cohort study. PLoS ONE. 2018;13(6):e0197967. doi: 10.1371/journal.pone.0197967.
    1. Schneider AG, Goodwin MD, Schelleman A, Bailey M, Johnson L, Bellomo R. Contrast-enhanced ultrasonography to evaluate changes in renal cortical microcirculation induced by noradrenaline: a pilot study. Crit Care. 2014;18(6):653. doi: 10.1186/s13054-014-0653-3.
    1. Dietrich C, Averkiou M, Correas JM, Lassau N, Leen E, Piscaglia F. An EFSUMB introduction into dynamic contrast-enhanced ultrasound (DCE-US) for quantification of tumour perfusion. Ultraschall Med. 2012;33(4):344–351. doi: 10.1055/s-0032-1313026.
    1. ESICM O behalf of the CDS of the, Ince C, Boerma EC, Cecconi M, Backer DD, Shapiro NI 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. Intens Care Med. 2018;44(3):281–99.
    1. Wharton G, Steeds R, Allen J, Phillips H, Jones R, Kanagala P, et al. A minimum dataset for a standard adult transthoracic echocardiogram: a guideline protocol from the British Society of Echocardiography. Echo Res Pract. 2015;2(1):G9–24. doi: 10.1530/ERP-14-0079.
    1. Langenberg C, Gobe G, Hood S, May CN, Bellomo R. Renal histopathology during experimental septic acute kidney injury and recovery&ast. Crit Care Med. 2014;42(1):e58–67. doi: 10.1097/CCM.0b013e3182a639da.
    1. Takasu O, Gaut JP, Watanabe E, To K, Fagley RE, Sato B, et al. Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med. 2013;187(5):509–517. doi: 10.1164/rccm.201211-1983OC.
    1. Schurek HJ, Jost U, Baumgartl H, Bertram H, Heckmann U. Evidence for a preglomerular oxygen diffusion shunt in rat renal cortex. Am J Physiol-Renal. 2002;259(6):F910–F915. doi: 10.1152/ajprenal.1990.259.6.F910.
    1. Molitoris BA, Sandoval RM. Kidney endothelial dysfunction: ischemia, localized infections and sepsis. Contrib Nephrol. 2011;174:108–118. doi: 10.1159/000329248.
    1. O’Connor PM, Anderson WP, Kett MM, Evans RG. Renal preglomerular arterial–venous o2 shunting is a structural anti-oxidant defence mechanism of the renal cortex. Clin Exp Pharmacol. 2006;33(7):637–641. doi: 10.1111/j.1440-1681.2006.04391.x.
    1. Edwards RM, Trizna W, Kinter LB. Renal microvascular effects of vasopressin and vasopressin antagonists. Am J Physiol-renal. 1989;256(2):F274–F278. doi: 10.1152/ajprenal.1989.256.2.F274.
    1. Sacha GL, Lam SW, Bauer SR. Did the beneficial renal outcomes with vasopressin VANISH? Ann Transl Medicine. 2016;4(S1):S67–67. doi: 10.21037/atm.2016.10.59.
    1. Tamaki T, Kiyomoto K, He H, Tomohiro A, Nishiyama A, Aki Y, et al. Vasodilation induced by vasopressin V2 receptor stimulation in afferent arterioles. Kidney Int. 1996;49(3):722–729. doi: 10.1038/ki.1996.101.
    1. Wan L, Langenberg C, Bellomo R, May CN. Angiotensin II in experimental hyperdynamic sepsis. Crit Care. 2009;13(6):R190–R290. doi: 10.1186/cc8185.
    1. Persichini R, Silva S, Teboul JL, Jozwiak M, Chemla D, Richard C, et al. Effects of norepinephrine on mean systemic pressure and venous return in human septic shock. Crit Care Med. 2012;40(12):3146–3153. doi: 10.1097/CCM.0b013e318260c6c3.
    1. Chen KP, Cavender S, Lee J, Feng M, Mark RG, Celi LA, et al. Peripheral edema, central venous pressure, and risk of AKI in critical illness. Clin J Am Soc Nephro. 2016;11(4):602–608. doi: 10.2215/CJN.08080715.
    1. Beaubien-Souligny W, Rola P, Haycock K, Bouchard J, Lamarche Y, Spiegel R, et al. Quantifying systemic congestion with Point-Of-Care ultrasound: development of the venous excess ultrasound grading system. Ultrasound J. 2020;12(1):16. doi: 10.1186/s13089-020-00163-w.
    1. Beaubien-Souligny W, Benkreira A, Robillard P, Bouabdallaoui N, Chassé M, Desjardins G, et al. Alterations in portal vein flow and intrarenal venous flow are associated with acute kidney injury after cardiac surgery: a prospective observational cohort study. J Am Hear Assoc Cardiovasc Cerebrovasc Dis. 2018;7(19):e009961. doi: 10.1161/JAHA.118.009961.
    1. Averkiou MA, Juang EK, Gallagher MK, Cuevas MA, Wilson SR, Barr RG, et al. Evaluation of the reproducibility of bolus transit quantification with contrast-enhanced ultrasound across multiple scanners and analysis software packages—a quantitative imaging biomarker alliance study. Invest Radiol. 2020;55(10):643–656. doi: 10.1097/RLI.0000000000000702.
    1. Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation. Crit Care. 2015;19(Suppl 3):S8. doi: 10.1186/cc14726.

Source: PubMed

3
Prenumerera