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

Not Applicable

Completed

Interventions: Diagnostic Test: GFR by Iohexol
Diagnostic Test: Urine Collection
Diagnostic Test: Blood samples

Brief Summary: 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.

Detailed Description: 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

Recruitment & Eligibility

Inclusion Criteria

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.

Arm && Interventions

Group	Intervention	Description
Discharged prior to 14 days	Blood samples	The group of patients were discharged before 14 days. GFR assessment at time of discharge and again at 1 year follow up.
Inhospital group at day 14	GFR by Iohexol	This group of sepsis participants remain hospitalized at day 14. GFR assessment is performed at inpatient day 14 and again at 1 year follow up.
Inhospital group at day 14	Urine Collection	This group of sepsis participants remain hospitalized at day 14. GFR assessment is performed at inpatient day 14 and again at 1 year follow up.
Discharged prior to 14 days	GFR by Iohexol	The group of patients were discharged before 14 days. GFR assessment at time of discharge and again at 1 year follow up.
Inhospital group at day 14	Blood samples	This group of sepsis participants remain hospitalized at day 14. GFR assessment is performed at inpatient day 14 and again at 1 year follow up.
Discharged prior to 14 days	Urine Collection	The group of patients were discharged before 14 days. GFR assessment at time of discharge and again at 1 year follow up.

Primary Outcome Measures

Name	Time	Method
Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline	For Arm 1 baseline is measured GFR at 14 days inhospital with sepsis or sepsis diagnosis. For Arm 2 baseline is measured GFR at discharge date prior to day 14 of hospitalizaton with sepsis or sepsis diagnosis.	The difference between a measured GFR with Iohexol and calculated GFR from creatinine.
Delta Curve Between Calculated GFR and GFR Measured by Iohexol at 1 Year Follow-up.	one year follow up for both arms	The difference between a measured GFR with Iohexol and calculated GFR from creatinine This was a one-time determination at 1 year follow-up

Secondary Outcome Measures

Name	Time	Method
Estimated GFR by Serum Creatinine	at 1 year follow-up	The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.
Calculated GFR by Urea Concentration and Creatinine Clearance	at one year follow-up	The urine will be collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of creatinine and urea concentration

Locations (1): UF Health at Shands hospital
🇺🇸
Gainesville, Florida, United States