With over one million operations a year, cardiac surgery with cardiopulmonary bypass is one
of the most common major surgical procedures worldwide (1). Acute kidney injury is a common
and serious postoperative complication of cardiopulmonary bypass and may affect 25% to 50% of
patients (2-4). Acute kidney injury carries significant costs (4) and is independently
associated with increased morbidity and mortality (2,3). Even minimal increments in plasma
creatinine are associated with an increase in mortality (5,6).
Multiple causes of cardiopulmonary bypass-associated acute kidney injury have been proposed,
including ischemia-reperfusion, generation of reactive oxygen species, hemolysis and
activation of inflammatory pathways (7-10). COMT LL genotype appears to increase the risk of
vasodilatory shock and AKI after cardiac surgery. To date, no simple, safe and effective
intervention to prevent cardiopulmonary bypass-associated acute kidney injury in a broad
patient population has been found (11-14).
Urinary acidity may enhance the generation and toxicity of reactive oxygen species induced by
cardiopulmonary bypass (10,15). Activation of complement during cardiac surgery (16) may also
participate in kidney injury. Urinary alkalinization may protect from kidney injury induced
by oxidant substances, iron-mediated free radical pathways, complement activation and tubular
hemoglobin cast formation (9,17,18). Of note, increasing urinary pH - in combination with
N-acetylcysteine (19,20) or without (21) - has recently been reported to attenuate acute
kidney injury in patients undergoing contrast-media infusion.
In a pilot double-blind, randomized controlled trial the investigators found sodium
bicarbonate to be efficacious, safe, inexpensive and easy to administer. These findings now
need to be confirmed or refuted by further clinical investigations in other geographic and
institutional settings.
Accordingly, the investigators hypothesized that urinary alkalinization might protect kidney
function in patients at increased risk of acute kidney injury undergoing cardiopulmonary
bypass needs to be confirmed in an international multicenter, double-blind, randomized
controlled trial of intravenous sodium bicarbonate.