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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. Interventional
study. Research
Institute. Sixteen adult Merino
ewes (n = 8/group). 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. 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. 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. |
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