Kidney Microcirculation As a Target for Innovative Therapies in AKI

Overview

Journal J Clin Med

Specialty General Medicine

Date 2021 Sep 28

PMID 34575154

Citations 6

Authors

Bulent Ergin

Sakir Akin

Can Ince

Affiliations

Soon will be listed here.

Abstract

Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of function and damage. The renal microcirculation plays a crucial role in maintaining the kidney's functional and structural integrity for oxygen and nutrient supply and waste product removal. However, alterations in microcirculation and oxygenation due to renal perfusion defects, hypoxia, renal tubular, and endothelial damage can result in AKI and the loss of renal function regardless of systemic hemodynamic changes. The unique structural organization of the renal microvasculature and the presence of autoregulation make it difficult to understand the mechanisms and the occurrence of AKI following disorders such as septic, hemorrhagic, or cardiogenic shock; ischemia/reperfusion; chronic heart failure; cardiorenal syndrome; and hemodilution. In this review, we describe the organization of microcirculation, autoregulation, and pathophysiological alterations leading to AKI. We then suggest innovative therapies focused on the protection of the renal microcirculation and oxygenation to prevent AKI.

Citing Articles

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References

Muslem R, Caliskan K, Akin S, Yasar Y, Sharma K, Gilotra N . Effect of Age and Renal Function on Survival After Left Ventricular Assist Device Implantation. Am J Cardiol. 2017; 120(12):2221-2225. DOI: 10.1016/j.amjcard.2017.08.045. View

Pallone T, Silldorff E, Turner M . Intrarenal blood flow: microvascular anatomy and the regulation of medullary perfusion. Clin Exp Pharmacol Physiol. 1998; 25(6):383-92. DOI: 10.1111/j.1440-1681.1998.tb02220.x. View

Morigi M, Benigni A . Mesenchymal stem cells and kidney repair. Nephrol Dial Transplant. 2012; 28(4):788-93. DOI: 10.1093/ndt/gfs556. View

Kruger-Genge A, Blocki A, Franke R, Jung F . Vascular Endothelial Cell Biology: An Update. Int J Mol Sci. 2019; 20(18). PMC: 6769656. DOI: 10.3390/ijms20184411. View

Just A . Mechanisms of renal blood flow autoregulation: dynamics and contributions. Am J Physiol Regul Integr Comp Physiol. 2006; 292(1):R1-17. DOI: 10.1152/ajpregu.00332.2006. View

Lopez-Novoa J, Quiros Y, Vicente L, Morales A, Lopez-Hernandez F . New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int. 2010; 79(1):33-45. DOI: 10.1038/ki.2010.337. View

Schwartz D, Mendonca M, Schwartz I, Xia Y, Satriano J, Wilson C . Inhibition of constitutive nitric oxide synthase (NOS) by nitric oxide generated by inducible NOS after lipopolysaccharide administration provokes renal dysfunction in rats. J Clin Invest. 1997; 100(2):439-48. PMC: 508208. DOI: 10.1172/JCI119551. View

Bruenger F, Kizner L, Weile J, Morshuis M, Gummert J . First successful combination of ECMO with cytokine removal therapy in cardiogenic septic shock: a case report. Int J Artif Organs. 2015; 38(2):113-6. DOI: 10.5301/ijao.5000382. View

Heyman S, Reichman J, Brezis M . Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia. Invest Radiol. 1999; 34(11):685-91. DOI: 10.1097/00004424-199911000-00004. View

10.

Ergin B, Kapucu A, Demirci-Tansel C, Ince C . The renal microcirculation in sepsis. Nephrol Dial Transplant. 2014; 30(2):169-77. DOI: 10.1093/ndt/gfu105. View

11.

Omoro S, Majid D, El-Dahr S, Navar L . Kinin influences on renal regional blood flow responses to angiotensin-converting enzyme inhibition in dogs. Am J Physiol. 1999; 276(2):F271-7. DOI: 10.1152/ajprenal.1999.276.2.F271. View

12.

Wijntjens G, Fengler K, Fuernau G, Jung C, den Uil C, Akin S . Prognostic implications of microcirculatory perfusion versus macrocirculatory perfusion in cardiogenic shock: a CULPRIT-SHOCK substudy. Eur Heart J Acute Cardiovasc Care. 2019; 9(2):108-119. DOI: 10.1177/2048872619870035. View

13.

Gardiner B, Thompson S, Ngo J, Smith D, Abdelkader A, Broughton B . Diffusive oxygen shunting between vessels in the preglomerular renal vasculature: anatomic observations and computational modeling. Am J Physiol Renal Physiol. 2012; 303(5):F605-18. DOI: 10.1152/ajprenal.00186.2012. View

14.

Ren Y, DAmbrosio M, Garvin J, Wang H, Carretero O . Prostaglandin E2 mediates connecting tubule glomerular feedback. Hypertension. 2013; 62(6):1123-8. PMC: 3882006. DOI: 10.1161/HYPERTENSIONAHA.113.02040. View

15.

Singh A, D Ramnath R, Foster R, Wylie E, Friden V, Dasgupta I . Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx. PLoS One. 2013; 8(2):e55852. PMC: 3573029. DOI: 10.1371/journal.pone.0055852. View

16.

Johannes T, Mik E, Nohe B, Unertl K, Ince C . Acute decrease in renal microvascular PO2 during acute normovolemic hemodilution. Am J Physiol Renal Physiol. 2006; 292(2):F796-803. DOI: 10.1152/ajprenal.00206.2006. View

17.

Hilty M, Akin S, Boerma C, Donati A, Erdem O, Giaccaglia P . Automated Algorithm Analysis of Sublingual Microcirculation in an International Multicentral Database Identifies Alterations Associated With Disease and Mechanism of Resuscitation. Crit Care Med. 2020; 48(10):e864-e875. DOI: 10.1097/CCM.0000000000004491. View

18.

Ren Y, DAmbrosio M, Garvin J, Wang H, Carretero O . Possible mediators of connecting tubule glomerular feedback. Hypertension. 2008; 53(2):319-23. PMC: 2697564. DOI: 10.1161/HYPERTENSIONAHA.108.124545. View

19.

Garland C, Hiley C, Dora K . EDHF: spreading the influence of the endothelium. Br J Pharmacol. 2010; 164(3):839-52. PMC: 3195909. DOI: 10.1111/j.1476-5381.2010.01148.x. View

20.

Morariu A, Maathuis M, Asgeirsdottir S, Leuvenink H, Boonstra P, van Oeveren W . Acute isovolemic hemodilution triggers proinflammatory and procoagulatory endothelial activation in vital organs: role of erythrocyte aggregation. Microcirculation. 2006; 13(5):397-409. DOI: 10.1080/10739680600745992. View