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In this prospective, randomized, placebo-controlled, double-blinded study, we determined the effects of two commonly used adjuncts, mannitol and dopamine, on β2-microglobulin (β2M) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). β2M excretion rate has been described as a sensitive marker of proximal renal tubular function. One-hundred patients with a preoperative serum creatinine level ≤1.5 mg/dL were prospectively randomized into 4 groups: 1) placebo, 2) mannitol 1 g/kg added to the CPB prime, 3) dopamine 2 μg · kg−1 · min−1 from the induction of anesthesia to 1 h post-CPB, or 4) mannitol plus dopamine. The primary outcome measure was β2M excretion rate at 1 h post-CPB. Secondary outcome measures included β2M excretion rate at 6 and 24 h post-CPB; urinary flow rate and creatinine clearance at 1, 6, and 24 h post-CPB; and the highest postoperative serum creatinine level. Length of intensive care stay and hospitalization, as well as adverse events, were also considered secondary outcomes. Dopamine significantly increased β2M excretion rate at 1 h post-CPB (2.48 ± 3.61 μg/min) compared with placebo (0.59 ± 1.04 μg/min; P = 0.001). This effect was not ameliorated by the addition of mannitol (β2M excretion rate, 2.05 ± 2.77 μg/min; P = 0.007 compared with placebo). β2M excretion rate was similar in patients given placebo or mannitol alone (P = 0.831). Rather than being a protective drug in the setting of CPB, dopamine alone or in combination with mannitol increases β2M excretion rate, which may be a measure of renal tubular dysfunction. The clinical implications of this increase and whether it is also seen in patients with established renal dysfunction undergoing CPB require additional investigation.