Tomas Luther: Aspects of renal blood flow and oxygenation in acute kidney injury during severe infections

Abstract

Acute kidney injury (AKI) is a common complication in patients treated in the intensive care unit (ICU). Severe infections/sepsis is the most common aetiology, and about half of patients treated in the ICU due to sepsis are affected. Although AKI often resolves over time, the development of AKI decreases the chances of surviving. This thesis aims to investigate mechanisms of AKI development related to renal blood flow and oxygenation, by using both animal experiments and novel techniques available to examine patients.

In Paper I, anaesthetised sheep were randomised to receive a bacterial infusion for 29 hours, or serve as controls. Isolated mitochondria from the animals’ renal cortex were investigated in vitro, at the beginning, and at the end of the experiment. Renal function deteriorated significantly in sheep with sepsis compared with the controls, and mitochondrial dysfunction by sepsis, comprised of a reduction of the RCR and an increased CII/CI-relation in State 3, was demonstrated in the sepsis group at the end of the experiment. However, renal cortical mitochondrial efficiency and uncoupling was unaffected by sepsis and cannot explain the discrepancy between oxygen consumption and tubular transport.

Paper II described and characterised AKI during the novel infection COVID-19, in a prospective cohort study of 57 patients in the ICU. Biomarkers for renal damage were measured in urine from 52 of the study participants. The results show that 89% of the study participants developed AKI. Oliguria was common and occurred early after ICU admission. The biomarkers in the urine were generally elevated, however, with only minor differences between patients stratified by severity of AKI.

In Paper III, 19 patients in the ICU due to COVID-19 were examined with magnetic resonance imaging (MRI). Renal blood flows, oxygenation, and water content were measured. The results show that patients with AKI had lower renal blood flows, both in the cortex and medulla, compared with those without. However, no differences regarding oxygenation or water content was demonstrated.

Paper IV investigated whether plasma expansion could affect renal blood flows in 17 of the study participants in Paper III. Ringer‘s acetate (7.5 ml/kg) was infused and the measurement with the magnetic camera was repeated. The results show that renal blood flows did not increase, either in patients with or without AKI, even though the increase in circulating blood volume resulted in higher blood pressure. However, patients without AKI had a lower perfusion in the renal medulla after plasma expansion.