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: Active, not recruiting
• Conditions: Sepsis
• Intervention / Treatment: Other: Iohexol; Other: Urine Collection; Other: 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.

One and/or all of the three ways for GFR assessment will be used, both at approximately day 14 or approximately at the day of discharge from the ICU and at the one year follow up :

1. Determine clearance of Iohexol from blood after Iohexol injection and/or
2. Determine apperance of Iohexol in urine after Iohexol injection (this would be the same injection as in one, and would not require two injections) and/or
3. A timed urine collection to determine clearance of urea and creatinine and/or
4. Estimated GFR using calculations with serum creatinine and cystatin C,

This will provide an opportunity to validate the different measurements.

• Study Type: Interventional
• Enrollment (Actual): 86
• 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
• Genders Eligible for Study: All

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
Active Comparator: Inhospital group at day 14; This group of sepsis participants will remain hospitalized after day 14. A normal saline dilution of Iohexol 0.5-1 ml will be given IV push. Blood or urine will be collected prior to the injection and at approximately 1, 2, 3, and 4 hours after the injection for glomerular filtration rate measurements. This test will be repeated in one year. In addition to or as an option would be to have a timed urine collection to determine clearance of urea and creatinine can be performed instead of the saline dilution of Iohexol 0.5-1 ml and/or an estimated of GFR using serum creatinine and cystatin C measurement using calculations from blood samples.	Other: Iohexol; Both groups of sepsis participants will receive a normal saline dilution of Iohexol 0.5-1 ml given by IV push. Blood or urine will be collected prior to the injection and at approximately 1, 2, 3, and 4 hours after the injection for glomerular filtration rate measurements. This test will be repeated in one year.; Other Names: omnipaque; Other: 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.; Other: 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 and cystatin C results.
Other: Released from hosptial prior to day 14; This group of sepsis participants will be released from the hospital prior to day 14. A normal saline dilution of Iohexol 0.5-1 ml will be given IV push. Blood or urine will be collected prior to the injection and at approximately 1, 2, 3, and 4 hours after the injection for glomerular filtration rate measurements. This test will be repeated in one year. In addition to or as an option would be to have a timed urine collection to determine clearance of urea and creatinine can be performed instead of the saline dilution of Iohexol 0.5-1 ml and/or an estimated of GFR using serum creatinine and cystatin C measurement using calculations from blood samples.	Other: Iohexol; Both groups of sepsis participants will receive a normal saline dilution of Iohexol 0.5-1 ml given by IV push. Blood or urine will be collected prior to the injection and at approximately 1, 2, 3, and 4 hours after the injection for glomerular filtration rate measurements. This test will be repeated in one year.; Other Names: omnipaque; Other: 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.; Other: 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 and cystatin C results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve versus time curve (AUC) of Iohexol	The decline in iohexol glomerular filtration rate at day 14 and 1 year follow-up between chronic crucial illness and control groups.	0, 1, 2, 3, and 4 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 14
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.	1 year
Urine Urea Concentration	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 urea concentration.	Day 14
Urine Urea Concentration	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 urea concentration.	1 year
Urine Creatinine Ratio	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.	Day 14
Urine Creatinine Ratio	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.	1 year

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): November 20, 2019
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

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