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

NCT02276066 | Completed Results DMC

• 2 other identifiers: IRB201400795-NP50GM111152-01
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

kidney dysfunction; chronic critical illness; sepsis; Glomerular filtration rate

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Estimated GFR by Serum Creatinine

  at 14 days inpatient hospitalization or at discharge date prior to day 14 inpatient hospitalization

• Estimated GFR by Serum Creatinine

  at 1 year follow-up

• Calculated GFR by Urea Concentration and Creatinine Clearance

  at 14 days inpatient hospitalization or at discharge date prior to day 14 inpatient hospitalization

• Calculated GFR by Urea Concentration and Creatinine Clearance

  at one year follow-up

Study Arms (2)

Inhospital group at day 14

EXPERIMENTAL

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; Diagnostic Test: Urine Collection; Diagnostic Test: Blood samples

Discharged prior to 14 days

ACTIVE COMPARATOR

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; Diagnostic Test: Urine Collection; Diagnostic Test: Blood samples

Interventions

GFR by Iohexol DIAGNOSTIC_TEST

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.

Also known as: omnipaque

Discharged prior to 14 days; Inhospital group at day 14

Urine Collection DIAGNOSTIC_TEST

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.

Discharged prior to 14 days; Inhospital group at day 14

Blood samples DIAGNOSTIC_TEST

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.

Discharged prior to 14 days; Inhospital group at day 14

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

UF Health at Shands hospital

Gainesville, Florida, 32610, United States

Location

Related Publications (1)

• 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.

  PMID: 31856021 DERIVED

MeSH Terms

Conditions

Sepsis

Interventions

Urine Specimen Collection; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Punctures; Surgical Procedures, Operative

Results Point of Contact

• Title: Mark S. Segal
• Organization: University of Florida Board of Trustees Contracts & Grants

segalms@medicine.ufl.edu

352-273-5357

Study Officials

• Mark Segal, M.D.

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: October 27, 2014
• Study Start: February 1, 2015
• Primary Completion: May 20, 2023
• Study Completion: May 20, 2023
• Last Updated: July 9, 2024
• Results First Posted: July 9, 2024

Record last verified: 2024-06

Locations

US (1)