Revealing Acute Kidney Injury: A Comprehensive Exploration in Cardiac Patients

Sebastian Buhl Rasmussen*

*Corresponding author for this work

Research output: ThesisPh.D. thesis

19 Downloads (Pure)

Abstract

Cardiac patients represent a population with increased kidney vulnerability, including a high risk of developing acute kidney injury (AKI). This complication is common both in the setting of cardiac surgery involving cardiopulmonary bypass and among patients experiencing severe circulatory failure, including those with out-of-hospital cardiac arrest (OHCA). Despite AKI posing an elevated risk of progressive kidney function decline and mortality, there is currently a lack of evidence regarding protective treatment strategies in clinical practice.

The PhD project aimed to obtain a more in-depth understanding of some of the pathophysiological mechanisms causing AKI in cardiac patients. The main findings were: Study I) In a retrospective observational study of cardiac surgery patients, elevated preoperative levels of soluble urokinasetype plasminogen activator receptor (suPAR) were significantly associated with a higher risk of postoperative AKI. A doubling of suPAR levels corresponded to an adjusted odds ratio of 1.62 (95% CI 1.26–2.09, P<0.001). Study II) In a porcine ex vivo kidney perfusion model, kidneys allocated to infusion with recombinant suPAR exhibited a significant decrease in blood flow (P=0.003), while exposed to similar perfusion pressures as controls (P=0.13). No statistically significant differences were observed between groups in terms of plasma albumin and creatinine, histopathology, or kidney injury- and inflammatory biomarkers. Study III) In a retrospective observational study of cardiac surgery patients, we found that an intraoperative increased duration of oxygen delivery (DO2) below 272 mL·min-1·m-2 was associated with an increased risk of AKI. Adjusted logistic regression revealed that only a duration of low DO2 of at least 30 minutes was associated with an increased risk of AKI (OR 1.50, 95% CI 1.07–2.10, P=0.018). Study IV) In a randomised clinical trial of resuscitated OHCA patients, we found that patients assigned to a low blood pressure and liberal oxygen target had a higher risk of developing AKI (OR 1.87, 95% CI 1.21–2.89, P=0.03) compared to those with high blood pressure and liberal oxygen targets. Multinominal logistic regression analysis revealed that the increased risk was primarily associated to mild stage AKI.

In conclusion, our study findings underscore the significance of preoperative suPAR levels as a prognostic biomarker for AKI development following cardiac surgery. Our experimental animal model suggests a potential mechanism whereby suPAR induces intrarenal vascular resistance, contributing to AKI pathogenesis. Furthermore, our observations emphasise the critical role of maintaining adequate oxygen delivery during cardiopulmonary bypass to mitigate AKI risk in cardiac surgery patients. Notably, our study reveals a novel association between low blood pressure and liberal oxygen targets and increased AKI risk in resuscitated OHCA patients, highlighting the complexity of AKI pathophysiology in different clinical contexts. These findings emphasise the need for tailored preventive strategies aimed at mitigating AKI risk in cardiac patients with increased kidney vulnerability.
Translated title of the contributionAfdækning af akut nyreskade: En omfattende undersøgelse af hjertepatienter
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
Supervisors/Advisors
  • Ravn, Hanne Berg, Principal supervisor
  • Svenningsen, Per, Co-supervisor
Date of defence13. Sept 2024
Publisher
DOIs
Publication statusPublished - 24. Jun 2024

Note re. dissertation

Print copy of the full thesis is restricted to reference use in the library.

Keywords

  • Acute kidney injury
  • Cardiac surgery
  • Cardiopulmonary bypass
  • Cardiac arrest
  • Animal model
  • Ex vivo

Fingerprint

Dive into the research topics of 'Revealing Acute Kidney Injury: A Comprehensive Exploration in Cardiac Patients'. Together they form a unique fingerprint.

Cite this