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. A disturbed relation between oxygen consumption (V̇o2) and renal Na+ transport has 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 compared with 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 animals) or served as controls (n = 8 animals) for 28 h. Renal V̇o2 and Na+ transport were repeatedly measured. Live cortical mitochondria were isolated at baseline and at the end of the experiment and assessed in vitro with high-resolution respirometry. Sepsis markedly reduced creatinine clearance, and the relation between Na+ transport and renal V̇o2 was decreased in septic sheep compared with control sheep. Cortical mitochondrial function was altered in septic sheep with a reduced respiratory control ratio (6.0 ± 1.5 vs. 8.2 ± 1.6, P = 0.006) and increased complex II-to-complex I ratio 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 composed of a reduction of the respiratory control ratio and an increased complex II/complex I relation in state 3 was demonstrated in an ovine model of SA-AKI. However, the disturbed relation between renal V̇o2 and renal Na+ transport could not be explained by a change in renal cortical mitochondrial efficiency or uncoupling.NEW & NOTEWORTHY We studied the function of renal cortical mitochondria in relation to oxygen consumption in an ovine model of sepsis with acute kidney injury. We demonstrated changes in the electron transport chain induced by sepsis consisting of a reduced respiratory control ratio mainly by a reduced complex I-mediated respiration. Neither an increase in mitochondrial uncoupling nor a reduction in mitochondrial efficiency was demonstrated and cannot explain why oxygen consumption was unaffected despite reduced tubular transport.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:324 |
|---|---|
| Enthalten in: |
American journal of physiology. Renal physiology - 324(2023), 6 vom: 01. Juni, Seite F571-F580 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Luther, Tomas [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Acute kidney injury |
|---|
| Anmerkungen: |
Date Completed 02.10.2023 Date Revised 02.10.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1152/ajprenal.00294.2022 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356062848 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356062848 | ||
| 003 | DE-627 | ||
| 005 | 20231226065649.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1152/ajprenal.00294.2022 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1186.xml |
| 035 | |a (DE-627)NLM356062848 | ||
| 035 | |a (NLM)37102685 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Luther, Tomas |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Renal mitochondrial dysfunction in ovine experimental sepsis-associated acute kidney injury |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.10.2023 | ||
| 500 | |a Date Revised 02.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Sheep develop sepsis-associated acute kidney injury (SA-AKI) during experimental sepsis despite normal to increased renal oxygen delivery. A disturbed relation between oxygen consumption (V̇o2) and renal Na+ transport has 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 compared with 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 animals) or served as controls (n = 8 animals) for 28 h. Renal V̇o2 and Na+ transport were repeatedly measured. Live cortical mitochondria were isolated at baseline and at the end of the experiment and assessed in vitro with high-resolution respirometry. Sepsis markedly reduced creatinine clearance, and the relation between Na+ transport and renal V̇o2 was decreased in septic sheep compared with control sheep. Cortical mitochondrial function was altered in septic sheep with a reduced respiratory control ratio (6.0 ± 1.5 vs. 8.2 ± 1.6, P = 0.006) and increased complex II-to-complex I ratio 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 composed of a reduction of the respiratory control ratio and an increased complex II/complex I relation in state 3 was demonstrated in an ovine model of SA-AKI. However, the disturbed relation between renal V̇o2 and renal Na+ transport could not be explained by a change in renal cortical mitochondrial efficiency or uncoupling.NEW & NOTEWORTHY We studied the function of renal cortical mitochondria in relation to oxygen consumption in an ovine model of sepsis with acute kidney injury. We demonstrated changes in the electron transport chain induced by sepsis consisting of a reduced respiratory control ratio mainly by a reduced complex I-mediated respiration. Neither an increase in mitochondrial uncoupling nor a reduction in mitochondrial efficiency was demonstrated and cannot explain why oxygen consumption was unaffected despite reduced tubular transport | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial, Veterinary | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a acute kidney injury | |
| 650 | 4 | |a mitochondria | |
| 650 | 4 | |a sepsis | |
| 650 | 7 | |a Oxygen |2 NLM | |
| 650 | 7 | |a S88TT14065 |2 NLM | |
| 700 | 1 | |a Bülow-Anderberg, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Persson, Patrik |e verfasserin |4 aut | |
| 700 | 1 | |a Franzén, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Skorup, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Wernerson, Annika |e verfasserin |4 aut | |
| 700 | 1 | |a Hultenby, Kjell |e verfasserin |4 aut | |
| 700 | 1 | |a Palm, Fredrik |e verfasserin |4 aut | |
| 700 | 1 | |a Schiffer, Tomas A |e verfasserin |4 aut | |
| 700 | 1 | |a Frithiof, Robert |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of physiology. Renal physiology |d 2000 |g 324(2023), 6 vom: 01. Juni, Seite F571-F580 |w (DE-627)NLM105736171 |x 1522-1466 |7 nnns |
| 773 | 1 | 8 | |g volume:324 |g year:2023 |g number:6 |g day:01 |g month:06 |g pages:F571-F580 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1152/ajprenal.00294.2022 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 324 |j 2023 |e 6 |b 01 |c 06 |h F571-F580 | ||