Renal mitochondrial dysfunction in ovine experimental Sepsis Associated Acute Kidney Injury

• 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. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)

Nyckelord

Anestesiologi och intensivvård

Anaesthesiology and Intensive Care

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