Luther 2023 Am J Physiol Renal Physiol

Luther T, Bülow Anderberg S, Persson P, Franzén S, Skorup P, Wernerson A, Hultenby K, Palm F, Schiffer TA, Frithiof R (2023) Renal mitochondrial dysfunction in ovine experimental sepsis associated acute kidney injury. https://doi.org/10.1152/ajprenal.00294.2022

» Am J Physiol Renal Physiol [Epub ahead of print]. PMID: 37102685 Open Access

Luther Tomas, Buelow Anderberg Sara, Persson Patrik, Franzen Stephanie, Skorup Paul, Wernerson Annika, Hultenby Kjell, Palm Fredrik, Schiffer Tomas A, Frithiof Robert (2023) Am J Physiol Renal Physiol

Abstract: Sheep develop sepsis associated acute kidney injury (SA-AKI) during experimental sepsis despite normal to increased renal oxygen delivery (DO₂). A disturbed relation between oxygen consumption (VO₂) and renal sodium transport have been demonstrated in sheep and in clinical studies of AKI, which could be explained by mitochondrial dysfunction. We investigated the function of isolated renal mitochondria in comparison to renal oxygen handling in an ovine hyperdynamic model of SA-AKI. Anesthetized sheep were randomized to either an infusion of live Escherichia Coli with resuscitative measures (Sepsis group, n=13) or served as controls (n=8) for 28 hours. Renal VO₂ and sodium transport were repeatedly measured. Live cortical mitochondria were isolated at baseline and end of experiment and assessed in vitro with high resolution respirometry. Sepsis markedly reduced creatinine clearance and the relation between sodium transport and renal VO₂ was decreased in septic compared with control sheep. Cortical mitochondrial function was altered in septic sheep with reduced Respiratory Control Ratio (RCR) (6.0±1.5 vs. 8.2±1.6; p=0.006) and increased Complex II/Complex I-ratio (CII/CI) during State 3 (1.6±0.2 vs. 1.3±0.1; p=0.0014) mainly due to decreased Complex I-dependent State 3 respiration (p=0.016). However, no differences in renal mitochondrial efficiency or mitochondrial uncoupling were found. In conclusion, renal mitochondrial dysfunction comprised of a reduction of the RCR and an increased CII/CI-relation in State 3 was demonstrated in an ovine model of SA-AKI. However, the disturbed relation between renal VO₂ and renal sodium transport could not be explained by a change in renal cortical mitochondrial efficiency or uncoupling. • Keywords: Acute kidney injury, Mitochondria, Sepsis • Bioblast editor: Plangger M • O2k-Network Lab: SE Uppsala Liss P

Labels: MiParea: Respiration  Pathology: Sepsis 

Organism: Other mammals  Tissue;cell: Kidney  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k 

2023-05