Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery

• acute kidney injury [ Time Frame: at randomization, at anesthsia induction, and postoperative days 1, 2, and 3, up to 6 months. ] [ Designated as safety issue: No ]
• delirium [ Time Frame: at randomization, daily postoperatively while in ICU, and up to 6 months ] [ Designated as safety issue: No ]

• estimated glomerular filtration [ Time Frame: baseline, day or surgery, and postoperative ] [ Designated as safety issue: No ]
• delirium and cognitive function [ Time Frame: baseline, postoperative, and at surgical follow-up ] [ Designated as safety issue: No ]

• dialysis [ Time Frame: until postoperative ICU discharge. ] [ Designated as safety issue: No ]
• urine markers of renal injury [ Time Frame: at randomization, anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, 12 hours postop, and POD 1, 2, 3. ] [ Designated as safety issue: No ]
• plasma markers of inflammation [ Time Frame: at randomization, anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3. ] [ Designated as safety issue: No ]
• liver enzymes [ Time Frame: postoperative day 1 ] [ Designated as safety issue: Yes ]
• stroke [ Time Frame: until postoperative ICU discharge ] [ Designated as safety issue: No ]
• death [ Time Frame: until postoperative hospital discharge & at 6 months ] [ Designated as safety issue: No ]
• plasma and urine markers of oxidative stress (f2-Isoprostanes, isofurans) [ Time Frame: at randomization, anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3. ] [ Designated as safety issue: No ]
• mitochondrial function [ Time Frame: at randomization, anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3. ] [ Designated as safety issue: No ]
  mtDNA copy number, lactate / pyruvate ratio, PGC-1alpha RNA expression

• dialysis [ Time Frame: postoperative ] [ Designated as safety issue: No ]
• urine markers of renal injury [ Time Frame: intraoperative and postoperative ] [ Designated as safety issue: No ]
• plasma markers of inflammation [ Time Frame: baseline, intraoperative, and postoperative ] [ Designated as safety issue: No ]
• liver enzymes [ Time Frame: postoperative day 1 ] [ Designated as safety issue: Yes ]
• stroke [ Time Frame: postoperative ] [ Designated as safety issue: No ]
• death [ Time Frame: postoperative ] [ Designated as safety issue: No ]

Aim1a: Statin naive patient's scheduled for cardiac surgery will be randomized to 80mg atorvastatin or placebo on the day prior to surgery and then 40mg daily thereafter until hospital discharge to test the hypothesis that short-term atorvastatin use decreases:

1. acute kidney injury following cardiac surgery.
2. postoperative delirium following cardiac surgery.

Aim1b: Patients using statins preoperatively will be randomized to atorvastatin 80mg or placebo on day of surgery and 40mg or placebo on postop day 1 with resumption of preoperative statin therapy on postop day 2 to test the hypothesis that short-term atorvastatin use decreases:

1. acute kidney injury following cardiac surgery.
2. postoperative delirium following cardiac surgery.

Endpoints include glomerular filtration, urine and plasma markers of renal dysfunction, markers of oxidative stress, mitochondrial function, systemic inflammatory markers, delirium, dialysis, stroke, myocardial infarction, time to extubation, ICU length of stay, and death.

• Acute Kidney Injury
• Post-Operative Delirium
• Icu Delirium
• Acute Renal Failure
• Delirium

• Drug: atorvastatin

  Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge.

  Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.

• Drug: placebo

  Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge.

  Aim 2 control: placebo the day of cardiac surgery and postop day 1.

• Experimental: statin
  Intervention: Drug: atorvastatin
• Placebo Comparator: placebo
  Intervention: Drug: placebo

Inclusion Criteria:

• open heart surgery

Exclusion Criteria:

• acute coronary syndrome with troponin leak or unrelenting angina
• liver dysfunction (transaminases 2x normal)
• history of myopathy or liver dysfunction on prior statin therapy
• use of potent CYP3A4 inhibitors such as antifungal azoles, macrolide antibiotics, HIV protease inhibitors, and nefazodone.
• pregnancy or breast feeding
• cyclosporine use
• dialysis
• history of kidney transplant
• fibrate users who cannot stop fibrate use.