TY - JOUR
T1 - Urinary Oxygenation as a Surrogate Measure of Medullary Oxygenation during Angiotensin II Therapy in Septic Acute Kidney Injury
AU - Lankadeva, Yugeesh R.
AU - Kosaka, Junko
AU - Evans, Roger G.
AU - Bellomo, Rinaldo
AU - May, Clive N.
N1 - Funding Information:
1Pre-clinical Critical Care Unit, Florey Institute of Neuroscience and Men- Acute kidney injury (AKI) is a frequent complication of tal Health, University of Melbourne, Melbourne, VIC, Australia. septic shock and is associated with increased mortality 2Cardiovascular Disease Program, Bioscience Discovery Institute and (1, 2). There is increasing evidence that AKI may result Department of Physiology, Monash University, Melbourne, VIC, Australia. partly from renal medullary tissue hypoxia (3–5). Indeed, 3Department of Intensive Care and Department of Medicine, Austin in a clinically relevant ovine model of hyperdynamic septic Health, Heidelberg and The Australian and New Zealand Intensive Care shock, early onset of selective medullary ischemia and hypoxia Research Centre, Melbourne, VIC, Australia. occurred despite increased global renal blood flow (RBF) and Research Council of Australia (1050672) and by funding from the Victo-Supported, in part, by grants from the National Health and Medical renal oxygen delivery (RDO2) (6, 7). These changes developed rian Government Operational Infrastructure Support Grant and the Jack several hours before the detection of AKI, supporting the Brockhoff Foundation (ID 4178). notion that medullary hypoxia due to intrarenal microcircula-dation Early Career Medical Research Grant and was supported by Post-Dr. Lankadeva’s institution received funding from a Jack Brockhoff Foun- tory dysfunction may contribute to loss of renal function in doctoral Fellowship from the National Heart Foundation of Australia (NHF, septic AKI (5–7).
Funding Information:
100869). Dr. Evans’ institution received funding from National Health Norepinephrine is the primary vasopressor used clini-funding from National Health and Medical Research Council of Australia, and Medical Research Council of Australia. Dr. May’s institution received cally to restore blood pressure in septic shock (8). However, National Heart Foundation of Australia, and the Jack Brockhoff Founda- catecholamines have several adverse effects, including induc-tion, and he received other support from a Victorian Government Opera- ing organ dysfunction and increased mortality in septic shock that they do not have any potential conflicts of interest.tional Infrastructure Support Grant. The remaining authors have disclosed (9–11). Furthermore, resuscitation with norepinephrine wors-For information regarding this article, E-mail: clive.may@florey.edu.au ened renal medullary ischemia and hypoxia in conscious sheep Copyright ©2017 by the Society of Critical Care Medicine and Wolters with established septic AKI (6). Angiotensin II is a potent vaso- Kluwer Health, Inc. All Rights Reserved. constrictor that is emerging as an effective adjunctive therapy DOI: 10.1097/CCM.0000000000002797 for patients with catecholamine-resistant hypotension (12–17).
Publisher Copyright:
© 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Objectives: Angiotensin II is an emerging therapy for septic acute kidney injury, but it is unknown if its vasoconstrictor action induces renal hypoxia. We therefore examined the effects of angiotensin II on intrarenal Po2 in ovine sepsis. We also assessed the validity of urinary Po2 as a surrogate measure of medullary Po2. Design: Interventional study. Setting: Research Institute. Subjects: Sixteen adult Merino ewes (n = 8/group). Interventions: Sheep were instrumented with fiber-optic probes in the renal cortex, medulla, and within a bladder catheter to measure Po2. Conscious sheep were infused with Escherichia coli for 32 hours. At 24-30 hours, angiotensin II (0.5-33.0 ng/kg/min) or saline vehicle was infused. Measurements and Main Results: Septic acute kidney injury was characterized by hypotension and a 60% ± 6% decrease in creatinine clearance. During sepsis, medullary Po2 decreased from 36 ± 1 to 30 ± 3 mm Hg after 1 hour and to 20 ± 2 mm Hg after 24 hours; at these times, urinary Po2 was 42 ± 2, 34 ± 2, and 23 ± 2 mm Hg. Increases in urinary neutrophil gelatinase-associated lipocalin (12% ± 3%) and serum creatinine (60% ± 23%) were only detected at 8 and 24 hours, respectively. IV infusion of angiotensin II, at 24 hours of sepsis, restored arterial pressure and improved creatinine clearance, while not exacerbating medullary or urinary hypoxia. Conclusions: In septic acute kidney injury, renal medullary and urinary hypoxia developed several hours before increases in currently used biomarkers. Angiotensin II transiently improved renal function without worsening medullary hypoxia. In septic acute kidney injury, angiotensin II appears to be a safe, effective therapy, and urinary Po2 may be used to detect medullary hypoxia.
AB - Objectives: Angiotensin II is an emerging therapy for septic acute kidney injury, but it is unknown if its vasoconstrictor action induces renal hypoxia. We therefore examined the effects of angiotensin II on intrarenal Po2 in ovine sepsis. We also assessed the validity of urinary Po2 as a surrogate measure of medullary Po2. Design: Interventional study. Setting: Research Institute. Subjects: Sixteen adult Merino ewes (n = 8/group). Interventions: Sheep were instrumented with fiber-optic probes in the renal cortex, medulla, and within a bladder catheter to measure Po2. Conscious sheep were infused with Escherichia coli for 32 hours. At 24-30 hours, angiotensin II (0.5-33.0 ng/kg/min) or saline vehicle was infused. Measurements and Main Results: Septic acute kidney injury was characterized by hypotension and a 60% ± 6% decrease in creatinine clearance. During sepsis, medullary Po2 decreased from 36 ± 1 to 30 ± 3 mm Hg after 1 hour and to 20 ± 2 mm Hg after 24 hours; at these times, urinary Po2 was 42 ± 2, 34 ± 2, and 23 ± 2 mm Hg. Increases in urinary neutrophil gelatinase-associated lipocalin (12% ± 3%) and serum creatinine (60% ± 23%) were only detected at 8 and 24 hours, respectively. IV infusion of angiotensin II, at 24 hours of sepsis, restored arterial pressure and improved creatinine clearance, while not exacerbating medullary or urinary hypoxia. Conclusions: In septic acute kidney injury, renal medullary and urinary hypoxia developed several hours before increases in currently used biomarkers. Angiotensin II transiently improved renal function without worsening medullary hypoxia. In septic acute kidney injury, angiotensin II appears to be a safe, effective therapy, and urinary Po2 may be used to detect medullary hypoxia.
KW - acute kidney injury
KW - angiotensin II
KW - biomarkers
KW - hypoxia
KW - sepsis
UR - http://www.scopus.com/inward/record.url?scp=85038229255&partnerID=8YFLogxK
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U2 - 10.1097/CCM.0000000000002797
DO - 10.1097/CCM.0000000000002797
M3 - Article
C2 - 29077618
AN - SCOPUS:85038229255
VL - 46
SP - e41-e48
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 1
ER -