no enrollment

We propose to determine the acute metabolic effects of intensive insulin therapy when administered to AKI patients with a particular focus on its effects on protein metabolism. We hypothesize that the degree of insulin resistance correlates with protein catabolism in critically ill patients with AKI, and that intensive insulin therapy will result in substantial reductions in both whole-body and skeletal muscle protein breakdown thereby improving overall protein balance. We also hypothesize that this therapy will have favorable effects on the inflammatory and oxidative stress profile of patients with AKI. The metabolic response to these interventions will be assessed through stable isotope infusion techniques, allowing for the most precise assessment of protein and energy homeostasis.

Inclusion Criteria:

• Adults ≥ 18 years of age admitted to the intensive care unit

• New onset acute kidney injury (AKI) or AKI superimposed on chronic kidney disease. AKI will be defined as:

  • an abrupt (within 48 hours) sustained increase (>24 hours) in serum creatinine of 2X baseline or
  • a reduction in urine output (documented oliguria of < 0.5 ml/kg/hr for >12 hours)

• Patients will be recruited for the study within 3-5 days following establishment of AKI

Exclusion Criteria:

• Institutionalized patient
• Unable to obtain consent from subject or legally recognized representative
• Pregnancy
• Patients receiving insulin within 12 hours of the study or patients with known diabetes mellitus.
• Patients receiving immunosuppressive medication including steroids (prednisone or equivalent dose ≥ 5 mg PO QD)
• AKI from urinary tract obstruction or a volume responsive pre-renal state.
• Liver Failure, defined as transaminase levels 3 times above the limit of normal or a total Bilirubin greater than 4 mg/dl.
• Evidence of active bleeding, defined as admission for bleeding (ex. GI bleed, ruptured aneurysm, trauma-related) coupled with an explained or unexplained decrease in hemoglobin of >2 points in the past 24 hours, or Hgb<8/Hct<24
• Ongoing myocardial ischemia or heart failure
• Life expectancy < 48 hours
• Patients without existing central venous access
• Hemodynamically unstable patients requiring active pressor titration, defined as an increase in current pressor dose by >20% or addition of a new pressor within 12 hours of initiating the study.
• History of Phenylketonuria (PKU) or other documented inborn errors of metabolism
• Hypokalemia, defined as a serum potassium of <3.0 mg/dl.
• Uncontrolled seizure disorder, defined as having seizure as a reason for admission, ongoing delirium tremens, or having had a seizure within 1 month of the study.