Acute kidney injury (AKI) is associated with renal medullary hypoxia. The medullary thick ascending limb (mTAL) in the renal outer medulla is most susceptible to hypoxic injury, due to marginal O2 supply and high O2 consumption. The objectives of this study were to document the earliest effect of hypoxia (8% O2 for 2.5 hrs) on the mTAL function, and to identify strategies to protect the mTAL from hypoxia. The earliest effect of hypoxia is large water diuresis, due to a fall in the medullary osmolality and increase in vasopressinase. Desmopressin acetate (dDAVP), a synthetic vasopressin analogue resistant to vasopressinase that may also increase O2 delivery, prevented water diuresis. A low dose (0.8mg/kg) of furosemide may significantly reduce the mTAL work without a large excretion of essential electrolytes. Large water diuresis may be diagnostically valuable in detecting renal tissue hypoxia, and dDAVP and furosemide may prevent AKI in the clinical setting.

Acute kidney injury (AKI) is associated with renal medullary hypoxia. The medullary thick ascending limb (mTAL) in the renal outer medulla is most susceptible to hypoxic injury, due to marginal O2 supply and high O2 consumption. The objectives of this study were to document the earliest effect of hypoxia (8% O2 for 2.5 hrs) on the mTAL function, and to identify strategies to protect the mTAL from hypoxia. The earliest effect of hypoxia is large water diuresis, due to a fall in the medullary osmolality and increase in vasopressinase. Desmopressin acetate (dDAVP), a synthetic vasopressin analogue resistant to vasopressinase that may also increase O2 delivery, prevented water diuresis. A low dose (0.8mg/kg) of furosemide may significantly reduce the mTAL work without a large excretion of essential electrolytes. Large water diuresis may be diagnostically valuable in detecting renal tissue hypoxia, and dDAVP and furosemide may prevent AKI in the clinical setting.