Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS

Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS): A New Horizon for Surgical Critical Care Subtitle. Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS

This study investigates the mechanism by which kidney dysfunction perpetuates inflammation, immunosuppression, and catabolism (PICS) in chronic critical illness. The investigators will test the hypothesis that persistent kidney dysfunction in sepsis associated by chronic critical illness contributes to decreased survival through the development of PICS. In chronic critical illness, the persistence of the inflammatory state may lead to capillary rarefication in the kidney causing accelerated chronic kidney disease. Progression of chronic kidney disease during chronic critical illness can drive PICS. Indeed, many of the features of chronic critical illness are consistent with the protein-energy malnutrition and muscle wasting associated with chronic kidney disease. Thus, the kidney can play a contributory role in chronic critical illness and PICS.

The main goal of this project is to measure kidney filtration function at day 14 or the day of discharge from hospital (whichever occurs first), in order to determine the presence and magnitude of persistent kidney dysfunction after sepsis episode and to longitudinally assess further decline of kidney function at one year follow-up. The measure of the glomerular filtration rate (GRF) in patients with chronic critical illness and controls (sepsis patients discharged from ICU before day 14) will be used to determine to what degree of kidney dysfunction contributes to decreased survival and increase in chronic kidney disease at year one after sepsis onset.

GFR assessment will be determined at approximately day 14 or approximately at the day of discharge from the ICU and at the one-year follow-up:

1. Determine GFR by Iohexol clearance and/or
2. Estimated GFR by urea concentration and creatinine clearance
3. Estimated GFR using calculations with serum creatinine

Inclusion Criteria:

• Presence in the surgery or trauma ICU
• Age of ≥18 years
• Entrance into our sepsis protocol
• Ability to obtain informed consent.

Exclusion Criteria:

• Expected lifespan of the patient is less than 3 months due to severe pre-existing comorbidities (ex. recurrent, advanced or metastatic cancer)
• Severe traumatic brain injury (evidence of neurologic injury on CT scan and a GCS <8)
• Refractory shock (i.e., patients who die within 12 hours)
• Uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel)
• Patient or patient's family are not committed to aggressive management of the patient's condition and/or the patient has a DNR/DNI on file.
• Severe CHF (NY Heart Association Class IV)
• Child-Pugh C liver disease or pre-liver transplant.
• Known HIV infection with CD4 count <200 cells/mm3
• Organ transplant recipient on immunosuppressive agents
• Known pregnancy and mother's that are breastfeeding
• Prisoners
• Institutionalized patients
• Inability to obtain informed consent.
• Chemotherapy or radiotherapy within 30 days prior to sepsis.
• End stage renal disease on admission.