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.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Diagnostic test: GFR by Iohexol; Diagnostic test: Urine Collection; Diagnostic test: Blood samples

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

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health at Shands hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhospital group at day 14; 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.	Diagnostic test: GFR by Iohexol; Participants may receive a normal saline dilution of Iohexol 0.5-1 ml given by IV push. Blood or urine will be collected and measured to determine glomerular filtration rate measurements. This test will be repeated in one year.; Other Names: omnipaque; Diagnostic test: Urine Collection; Both groups of sepsis participants will have urine 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. This test will be repeated in one year.; Diagnostic test: Blood samples; Both groups of sepsis participants will provide peripheral blood samples to the research staff. The samples will be sent to the laboratory for serum creatinine results. This test will be repeated in one year.
Active Comparator: Discharged prior to 14 days; The group of patients were discharged before 14 days. GFR assessment at time of discharge and again at 1 year follow up.	Diagnostic test: GFR by Iohexol; Participants may receive a normal saline dilution of Iohexol 0.5-1 ml given by IV push. Blood or urine will be collected and measured to determine glomerular filtration rate measurements. This test will be repeated in one year.; Other Names: omnipaque; Diagnostic test: Urine Collection; Both groups of sepsis participants will have urine 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. This test will be repeated in one year.; Diagnostic test: Blood samples; Both groups of sepsis participants will provide peripheral blood samples to the research staff. The samples will be sent to the laboratory for serum creatinine results. This test will be repeated in one year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline	The difference between a measured GFR with Iohexol and calculated GFR from creatinine.	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.
Delta Curve Between Calculated GFR and GFR Measured by Iohexol at 1 Year Follow-up.	The difference between a measured GFR with Iohexol and calculated GFR from creatinine This was a one-time determination at 1 year follow-up	one year follow up for both arms

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated GFR by Serum Creatinine	The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.	at 14 days inpatient hospitalization or at discharge date prior to day 14 inpatient hospitalization
Estimated GFR by Serum Creatinine	The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.	at 1 year follow-up
Calculated GFR by Urea Concentration and Creatinine Clearance	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	at 14 days inpatient hospitalization or at discharge date prior to day 14 inpatient hospitalization
Calculated GFR by Urea Concentration and Creatinine Clearance	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	at one year follow-up

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Mark Segal, M.D., University of Florida

Publications and helpful links

General Publications

• Loftus TJ, Wu Q, Wang Z, Lysak N, Moore FA, Bihorac A, Efron PA, Mohr AM, Brakenridge SC. Delayed interhospital transfer of critically ill patients with surgical sepsis. J Trauma Acute Care Surg. 2020 Jan;88(1):169-175. doi: 10.1097/TA.0000000000002476.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): May 20, 2023
• Study Completion (Actual): May 20, 2023

Study Registration Dates

• First Submitted: October 23, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimated): October 27, 2014

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: June 13, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: sepsis; Glomerular filtration rate; chronic critical illness; kidney dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: IRB201400795-N; P50GM111152-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No