Does Nesiritide Provide Renal Protection

This will be a randomized, prospective blinded pilot study comparing nesiritide to placebo
in patients undergoing aortic arch, ascending aorta, aortic valve or mitral valve surgery
with baseline GFR 30-90ml/min. A total of 40 patients will be enrolled over 20 months.
Patients will be randomized to either placebo or nesiritide (administered prophylactically
starting in the operating room prior to incision at 0.01 mcg/kg /minute with no bolus and
continued for 48 hours).

Primary Endpoint:

• RIFLE( defines three grades of severity - risk (class R), injury (class I) and failure
(class F)) / AKIN (Acute Kidney Injury Network) Criteria for acute kidney injury= rise in
creatinine > 1.5X baseline.

Secondary Endpoints:

- Differences in neutrophil genomic expression patterns between patients receiving
nesiritide and placebo.

- Differences in neutrophil genomic expression patterns between patients with acute
kidney injury ("AKI" as measured by primary endpoint) and those without AKI.

- Urinary NGAL measurements 2 hours after end of cardiopulmonary bypass (CPB).

- Serum Endothelin-1 levels (area under the curve AUC first 24 hours after CPB).

- Cytokine profile of pro-inflammatory cytokine TNF (AUC first 24 hours after CPB).

- Cytokine profile of pro-inflammatory cytokine IL-6 (AUC first 24 hours after CPB).

- Exploratory study of 21 additional cytokine profiles on Luminex plate (area under the
curve AUC first 24 hours after CPB).

- Surgical adverse events (including: bleeding, stroke, respiratory failure, arrhythmias,
infections, others).

- Calculated glomerular filtration rate (GFR) first 7 days and 30 days.

- Dialysis / Renal replacement therapy.

- 30-day mortality

- Urine output initial 24 and 48hours.

- Length of ventilator intubation, ICU and Hospital length of stay

- Left ventricular mechanics: twist, circumferential strain and radial displacement.

Inclusion Criteria:

- Patients undergoing surgery on their aortic arch, ascending aorta, or having aortic
valve or mitral valve surgery

- Baseline MDRD (modification of diet in renal disease) calculated GFR (Glomerular
Filtration Rate) 30-90 ml/min.

- Signed Informed Consent

Exclusion Criteria:

- Age <18 or >80

- Ejection Fraction <30%.

- Presence of endocarditis or other infection.

- Presence or anticipated use of an intra-aortic balloon pump.

- History of an organ transplant.

- History of an adverse reaction to nesiritide.

- Surgery performed without cardiopulmonary bypass.

- Receiving Aprotinin

- Dopamine administered in doses <5 mcg /kg min.

- Women of child bearing potential or pregnant or breastfeeding.

- Participation in any other investigational trial

- Jehovah Witness

- Bleeding Disorder

- Active Endocarditis